bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–09–20
57 papers selected by
Luca Bolliger, lxBio
  1. Nursing Roles in Diabetic Foot Ulcer Prevention, Wound Management, and Digital Monitoring.
  2. Precision bacteriophage therapy for multidrug-resistant recurrent urinary tract infections: From biological rationale to clinical translation in Taiwan.
  3. Negative pressure wound therapy versus standard wound care for diabetic foot ulcers: a systematic review and meta-analysis of healing and limb outcomes.
  4. First characterization of Staphylococcus felis in diabetic foot osteomyelitis: from intracellular persistence to phage treatment.
  5. Phage bioinformatics tools: a review of computational approaches for bacteriophage research.
  6. The Chronic Wound Microbiome: Dynamics and Treatment Response.
  7. Biofilm-driven antimicrobial resistance: A review of molecular mechanisms, clinical implications, and therapeutic innovation.
  8. Bacteriophages in humans: From discovery and mechanisms to therapeutic promise in combating disease.
  9. Genomic and functional characterization of novel therapeutic lytic bacteriophages targeting multidrug-resistant Enterobacter cloacae.
  10. Engineered Bacteriophages in Cancer Immunotherapy: Emerging Concepts and Potential Integration with CAR-T Cell Therapy.
  11. Single-cell RNA sequencing in diabetic foot ulcers: pathogenesis, biomarkers, and translational potential.
  12. Healing or Harming? Navigating Resistance and Rationality in Diabetic Foot Ulcer Antibiotic Therapy: A Retrospective Observational Study.
  13. Bacteria-induced immunity: from homeostasis to immune subversion in periodontitis.
  14. Absolute quantification by mouthwash testing screens severe periodontitis and tracks species-specific microbial response to periodontal therapy.
  15. Autoimmune disease-associated pathobionts: mechanisms and therapeutic potential of phage-based approaches.
  16. Substrate morphology modulates bacteriophage mobility and alters bactericidal potency.
  17. Retraction Note: Phage therapy and the microbiome in hematologic malignancies: opportunities, mechanisms, and early evidence.
  18. The Oral Microbiome-Inflammaging Axis in Elderly Periodontitis: Emerging Immunopathogenic and Systemic Mechanisms.
  19. More than an infection: the ecological puzzle of recurrent urinary tract infections.
  20. Shengji ointment accelerates diabetic foot ulcer wound healing by regulating inflammatory microenvironment.
  21. The Cost of Control: Financial and Administrative Burdens of Limited Distribution Network Changes in Cystic Fibrosis.
  22. Design and evaluation of a custom contoured pneumatic insole for active plantar pressure offloading.
  23. Bacterial profile and antimicrobial resistance patterns of infected diabetic foot ulcers in low- and middle-income countries: a systematic review and meta‑analysis.
  24. From dysbiosis to resilience: Microbiome engineering for sustainable shrimp aquaculture.
  25. Periodontal disease and Alzheimer's disease: A systematic review.
  26. Causes and Contributing Factors of In-Hospital and Post-Discharge Mortality Among Patients With Severe Acute Respiratory Infection in Low- and Middle-Income Countries: A Scoping Review.
  27. Gut microbiome dynamics in acute infectious diarrhea: A conceptual framework from acute dysbiosis toward precision restoration (Review).
  28. Managing Complex Wounds After Treatment Failure: Patterns Identified in an Advanced Wound Healing Center.
  29. Paired oral clinical specimens reveal the underlying ecology supporting the emergence of inflammophilic microbiome communities.
  30. From colonisation to immune evasion: a synthesis of the interaction strategies that drive Staphylococcus aureus infection.
  31. Polymicrobial-driven NLRP6 inflammasome regulates IL-1β production and alveolar bone loss in a murine model of periodontitis.
  32. The impact of microbiome diversity and composition on host health and susceptibility to disease across amphibian life stages.
  33. Isolation and Characterization of Lytic Bacteriophages Targeting Clinical Staphylococcus Other Than S. aureus.
  34. From mouth to brain: Linking periodontal and peri-implant dysbiosis to systemic inflammation and neuropathology.
  35. Amino acid homorepeats in tape measure proteins correlate with bacteriophage tail length.
  36. Offloading strategies for diabetic foot ulcers: A systematic review and network meta-analysis of randomized controlled trials.
  37. Multidrug resistance and biofilm formation among bacterial isolates from chronic wounds in animals: evaluation of anti-biofilm activity.
  38. Gut microbiota dysbiosis and the gut-lung axis in COPD: mechanisms, clinical relevance, and microbiota-targeted interventions.
  39. Mechanistic Pathways of Wound Healing: From Hemostasis to Scar-Free Regeneration.
  40. The gut microbiota in Graves' disease: mechanistic insights and clinical implications.
  41. Foundation Models for Microbiome Research: From Sequence Semantics to Community Dynamics and Multimodal World Models.
  42. The 100 Most-Cited Articles on Periodontal Disease and Atherosclerosis: A Bibliometric Study (1989-2025).
  43. A severity-aware multi-task CNN-transformer framework for explainable diabetic foot ulcer triage and mobile deployment.
  44. The application of artificial intelligence in systemic lupus erythematosus: a bibliometric analysis of current trends and future directions.
  45. Harmonized multi-cohort analysis of oral microbiome development during early lifetime.
  46. In-host adaptation of Staphylococcus aureus during recurrent prosthetic joint infections: a retrospective longitudinal study.
  47. From oral infection to pulmonary inflammation: periodontal pathogens and their potential role in COPD susceptibility.
  48. Prediction Models for Periprosthetic Joint Infection: A Systematic Review of Traditional and Machine Learning Approaches.
  49. A Bacillus Phage From Bangladeshi Soil, Phage APU1: Genomic Characterisation and Comparative Genomic Analysis.
  50. Lung microbiome alterations in idiopathic pulmonary fibrosis and hypersensitivity pneumonitis: A systematic review with insights into microbiome-host interactions and the gut-lung axis.
  51. The Oral Microbiome in Oral Cavity Cancer: Mechanisms of Carcinogenesis, Biomarkers, and Therapeutic Implications.
  52. Machine learning to differentiate colonization from infection in multidrug-resistant Gram-negative bacteria: implications for further research.
  53. Prophage-encoding engineered bacteria enable prophylactic lytic phage therapy for enteric infection in mice.
  54. Refining the Taxonomy of Wound Healing Patterns in Periodontal Therapy.
  55. Association Between Periodontitis Severity and Oral Health-Related Quality of Life: A Cross-Sectional Study Using the 2017 Periodontitis Classification.
  56. Pathological Microenvironment-Guided Smart Hydrogels for Periodontitis Therapy.
  57. Molecular mimicry and functional convergence of bacterial proteins in host-microbe interactions.
  1. J Vis Exp. 2026 09 11.
    Nursing Roles in Diabetic Foot Ulcer Prevention, Wound Management, and Digital Monitoring.
    Dangqin Ding, Aya Hamoud Alhaskawi, Jiayan Shen, Minwei Yang, Yuanjing Liu, Liping He, Ahmad Alhaskawi, Xiaodi Zou, Weijie Zhou, Jiaqi Li, Hui Lu.
      Diabetic foot ulcers (DFUs) remain a major cause of infection, hospitalization, impaired quality of life, and non-traumatic lower-limb amputation among people with diabetes. Effective management requires coordinated prevention, structured foot-risk assessment, pressure offloading, wound care, infection surveillance, patient education, and multidisciplinary follow-up. This narrative review examines the nurse-led and nurse-supported components of contemporary DFU care. Nurses contribute through routine foot and wound assessment, reinforcement of preventive behaviors and treatment adherence, support for offloading, monitoring after debridement and advanced wound therapies, and early recognition of infection, ischemia, osteomyelitis, or clinical deterioration. Patient and caregiver education should be practical, individualized, and reinforced over time. Current evidence most consistently supports improvements in foot-care knowledge, self-management behavior, and healthcare-provider competence, whereas effects on ulcer recurrence, hospitalization, and amputation remain less certain. Digital technologies, including telemedicine, wearable sensors, mobile health platforms, and artificial intelligence-based wound assessment, may improve access to monitoring, communication, and early risk detection. However, their evidence base and clinical readiness vary, and improved monitoring does not necessarily translate into better healing or fewer amputations. Their usefulness depends on patient training, data quality, governance, timely professional review, and integration with safe referral pathways. Digital tools should therefore support, rather than replace, direct clinical assessment and multidisciplinary decision-making. Overall, nursing practice is essential for translating evidence-based DFU management into continuous, coordinated, and patient-centered care.
    DOI:  https://doi.org/10.3791/71452
  2. Tzu Chi Med J. 2026 Oct-Dec;38(4):38(4): 423-433
    Precision bacteriophage therapy for multidrug-resistant recurrent urinary tract infections: From biological rationale to clinical translation in Taiwan.
    Ling-Chun Lin, Hann-Chorng Kuo, Nien-Tsung Lin.
      Recurrent urinary tract infections (rUTIs), driven by multidrug-resistant (MDR) uropathogens, intracellular reservoirs, and biofilms, progressively circumvent conventional antibiotic therapy. Bacteriophage (phage) therapy has re-emerged as a precision medicine strategy offering narrow host specificity, self-amplification at the infection site, and intrinsic antibiofilm activity via depolymerases. This minireview evaluates the biological rationale and translational evidence for phage therapy in MDR-rUTIs, emphasizing the clinical distinction between standardized trials for acute uncomplicated infections and personalized salvage interventions for complex rUTIs. Clinical data suggest that personalized, susceptibility-matched phage regimens have demonstrated encouraging clinical outcomes in reported cases; however, these findings are primarily based on case reports and small observational series, necessitating further validation through large-scale randomized controlled trials. In Taiwan, where extended-spectrum β-lactamase-producing Escherichia coli is prevalent, phage therapy is shaping its regulatory landscape through special-case and compassionate-use pathways. Strategic opportunities exist to leverage Taiwan's National Health Insurance database and centralized good manufacturing practices-compliant biobanks to transition phages into a regulated component of antimicrobial stewardship. However, addressing biological and logistical hurdles - specifically neutralizing antibody formation and manufacturing scalability - remains essential for broad implementation. This review provides a framework for integrating phage therapy into precision care pathways for rUTIs in the Asia-Pacific region.
    Keywords:  Bacteriophages; Multidrug resistance; Precision medicine; Recurrent urinary tract infections; Taiwan
    DOI:  https://doi.org/10.4103/tcmj.TCMJ-D-26-00021
  3. Front Endocrinol (Lausanne). 2026 ;17 1850122
    Negative pressure wound therapy versus standard wound care for diabetic foot ulcers: a systematic review and meta-analysis of healing and limb outcomes.
    Chao Niu, Kunpeng Fu, Xiuxiao Chen, Yanyang Wang.
       Background: Diabetic foot ulcers (DFUs) are major diabetes-related complications that often require prolonged wound care, debridement, or limb-salvage surgery. Negative pressure wound therapy (NPWT) is widely used as an adjunct, but its comparative effectiveness remains debated.
    Objective: To meta-analyze the efficacy and safety of NPWT versus standard wound care in adults with DFUs.
    Methods: PubMed/MEDLINE, Cochrane CENTRAL, EMBASE, and Web of Science were searched from January 2000 to January 2025 for randomized, quasi-randomized, or prospective controlled studies. The primary outcome was complete healing; secondary outcomes were time to healing, amputation, wound infection, length of stay, and adverse events. Binary outcomes were pooled with random-effects (REML) models using the Hartung-Knapp adjustment; we report 95% prediction intervals and leave-one-out analyses and graded certainty using GRADE.
    Results: Nineteen studies (2,046 patients) were included. NPWT improved complete healing. Because one large trial was a clear statistical outlier driving heterogeneity (I2 = 83%), the primary healing estimate excludes it: risk ratio (RR) 1.42 (95% CI 1.15-1.74; prediction interval 1.08-1.85; I2 = 33%); the full-set estimate including that trial (RR 1.67, 1.24-2.25, P = 0.004) is reported secondarily. The benefit was robust to leave-one-out analysis (RR 1.42-1.78) and to exclusion of high-risk-of-bias studies. For amputation (5 studies) and wound infection (3 studies), point estimates favored NPWT (RR 0.46 and 0.52) but Hartung-Knapp intervals were wide and crossed 1 (0.18-1.17 and 0.25-1.06); with so few studies these reflect insufficient evidence rather than a demonstrated absence of effect. Time-to-healing data were too incompatible to pool (I2 = 91%) and are summarized narratively.
    Conclusions: NPWT is associated with improved complete wound healing in adults with DFUs; this conclusion rests on the most defensible, outlier-excluded analysis and is robust to conservative adjustment, leave-one-out analysis, and exclusion of high-risk studies. Evidence on amputation and infection is insufficient rather than negative. NPWT may be considered for selected patients with deeper or high-risk DFUs when perfusion is adequate and standard care has been insufficient.
    Keywords:  amputation; diabetic foot ulcer; infection; meta-analysis; negative pressure wound therapy; systematic review; wound healing
    DOI:  https://doi.org/10.3389/fendo.2026.1850122
  4. Microbiol Spectr. 2026 Sep 14. e0234025
    First characterization of Staphylococcus felis in diabetic foot osteomyelitis: from intracellular persistence to phage treatment.
    Cynthia N Abi Najem, Chloé Magnan, Lucile Plumet, Vincent Jean-Pierre, Sophie Schuldiner, Albert Sotto, Jean-Philippe Lavigne, Virginie Molle.
      Staphylococcus felis is a coagulase-negative Staphylococcus (CoNS) primarily associated with the feline microbiota and only rarely reported in human disease. Here, we report its implication in diabetic foot osteomyelitis, and provide the first comprehensive characterization of its pathogenic potential. Two isolates (NSF001 and NSF002), recovered 5 months apart from bone biopsies of the same patient, were analyzed for growth kinetics, biofilm formation, and intracellular persistence in macrophages and osteoblasts. Both isolates proliferated efficiently, produced robust biofilm, and persisted within host cells, most markedly in osteoblasts. In a zebrafish embryo infection model, both isolates caused significant mortality, confirming their pathogenic potential in vivo. Whole-genome sequencing revealed conserved virulence determinants, a narrow resistome, and strain-specific genomic variations affecting genes involved in virulence regulation, phage defense, and iron acquisition. The lytic phage SAVM02, previously characterized for activity against other Staphylococcus species, effectively inhibited S. felis growth in vitro and conferred protection in vivo against lethal infection. Notably, the two sequential isolates differed in their in vivo virulence and phage susceptibility, paralleling these within-host microevolutionary changes and illustrating bacterial adaptation during chronic infection. Altogether, this study establishes S. felis as a CoNS capable of intracellular persistence, biofilm formation, and in vivo virulence in chronic human infection. Our findings also highlight the therapeutic potential of lytic phages against virulent CoNS species and support further investigation of phage therapy for chronic staphylococcal infections.IMPORTANCECoagulase-negative staphylococci (CoNS) are increasingly recognized as genuine agents of chronic infection, yet the pathogenic capacity of most individual species remains undefined. Staphylococcus felis, a commensal of cats only exceptionally reported in humans, had never been implicated in a chronic human infection. Here, we describe two sequential S. felis isolates recovered from bone biopsies of a patient with diabetic foot osteomyelitis and show that this species combines biofilm formation, intracellular persistence in macrophages and osteoblasts, and lethality in a zebrafish embryo model. Whole-genome comparison of the two isolates uncovered microevolutionary changes, most notably in iron-acquisition and genome-defense loci, that paralleled differences in virulence and phage susceptibility. These findings extend the list of CoNS capable of causing invasive human disease and provide a rationale for lytic phage therapy against emerging, difficult-to-treat staphylococcal pathogens.
    Keywords:  Staphylococcus felis; coagulase-negative staphylococci; diabetic foot osteomyelitis; intracellular persistence; phage therapy; whole-genome sequencing; zebrafish model
    DOI:  https://doi.org/10.1128/spectrum.02340-25
  5. Brief Bioinform. 2026 Sep 01. pii: bbag494. [Epub ahead of print]27(5):
    Phage bioinformatics tools: a review of computational approaches for bacteriophage research.
    Sean Jia Le Pang, Soon Keong Wee, Eric Peng Huat Yap.
      Rising clinical interest in phage therapy and the exponential growth of metagenomic sequence catalogues have driven a rapid expansion of bacteriophage bioinformatics. More than 80 dedicated tools, mostly published since 2020, now span identification, assembly, annotation, taxonomy, lifestyle prediction, defence-system detection, and host prediction. Aimed at experienced practitioners and developers, this review synthesizes the field through the lens of three successive computational paradigms: sequence homology, bounded by database completeness; machine learning, constrained by labelled training data; and foundation models, which now achieve Matthews correlation coefficients above 0.95 in identification tasks and, through structure-informed prediction, raise functional annotation to over half of phage genes. Furthermore, we map the upstream components, namely, gene callers, homology engines, protein language models, and structural search tools, that underpin most downstream pipelines, exposing shared infrastructure and ecosystem-level fragility when dependencies change. To translate this into practice, we propose web-based and command-line reference workflows calibrated to user expertise and sample types. Finally, we set an agenda for the next wave of tool development. Roughly half of phage genes still resist functional annotation despite structural methods; no broadly generalizable strain-level host predictor exists for phage therapy; varying true-positive rates (0%-97%) underscore the absence of standardized community benchmarks analogous to Critical Assessment of Structure Prediction or Critical Assessment of Metagenome Interpretation. As generative genome models begin designing synthetic phages, progress will depend less on producing standalone tools than on rigorous evaluation, interoperable infrastructure, and clinically meaningful prediction targets.
    Keywords:  bacteriophage; bioinformatics; foundation models; host prediction; protein structure; viral metagenomics
    DOI:  https://doi.org/10.1093/bib/bbag494
  6. Cells. 2026 Aug 27. pii: 1553. [Epub ahead of print]15(17):
    The Chronic Wound Microbiome: Dynamics and Treatment Response.
    Ilaria Cavallo, Francesca Sivori, Massimo Francalancia, Alessandro Greco, Mauro Truglio, Fulvia Pimpinelli, Enea Gino Di Domenico.
      Chronic ulcers require prolonged care and carry an increased risk of infection and limb loss. Sequencing studies of diabetic foot ulcers, venous leg ulcers, and pressure ulcers have revealed dynamic, patient-specific microbial communities whose composition varies with local tissue conditions and treatment exposure. This review examines changes in microbial burden and community structure during wound-bed and antimicrobial interventions and their relationships with healing. Observed shifts may contribute to therapeutic effects, reflect direct perturbation of the community, or follow tissue recovery. However, most studies are small, heterogeneous, and uncontrolled, limiting causal inference. No published randomized trial has shown that treatment selection informed by sequencing-based microbial profiling improves wound healing. A central translational challenge is to determine whether baseline microbial features reproducibly predict responses to defined interventions. Progress will therefore require prospective longitudinal studies integrating sequencing with quantitative culture, isolate phenotyping, antimicrobial susceptibility testing, biofilm assays, and standardized clinical data. Such studies should establish whether microbiome profiling adds clinically useful information to conventional wound assessment and microbiological testing.
    Keywords:  antibiotics; biofilm; chronic wounds; debridement; microbiome; skin ulcers
    DOI:  https://doi.org/10.3390/cells15171553
  7. Infect Genet Evol. 2026 Sep 17. pii: S1567-1348(26)00152-8. [Epub ahead of print]145 106028
    Biofilm-driven antimicrobial resistance: A review of molecular mechanisms, clinical implications, and therapeutic innovation.
    Tanvee Chakraborty, Madhuchhanda Chatterjee, Sayanika Das, Aditi Roy, Sudha Ramaiah, Anand Anbarasu.
      Biofilms are structured microbial communities embedded within a self-produced extracellular polymeric substance matrix that promotes persistence under adverse environmental and host-associated conditions. Their clinical importance is primarily associated with increased antimicrobial tolerance, evasion of host immune responses, and persistence in chronic and medical device-associated infections. This review provides an integrated overview of the molecular and genetic determinants governing biofilm development, including surface attachment, matrix biosynthesis, quorum-sensing networks, cyclic-di-GMP signaling, maturation, and dispersal. The contribution of key matrix components, including polysaccharides, extracellular proteins, extracellular DNA, lipids, and water, is considered in relation to biofilm architecture, stability, and cellular adaptation. Clinically relevant biofilm-forming microorganisms, including Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Candida albicans, are major contributors to chronic infections, healthcare-associated infections, and infections associated with medical devices. The mechanisms contributing to reduced antimicrobial susceptibility in biofilms include restricted drug penetration, metabolic heterogeneity, persister-cell formation, efflux activity, stress-response pathways, and horizontal gene transfer. Conventional in vitro and in vivo biofilm models often fail to fully mimic the complex conditions present within the human host, thereby limiting the clinical translation and therapeutic relevance of experimental findings. In addition, emerging antibiofilm interventions, including quorum-sensing inhibitors, matrix-degrading enzymes, nanoparticle-based delivery systems, antimicrobial peptides, and bacteriophage therapy, are considered alongside the growing application of multi-omics and artificial intelligence for biomarker discovery and therapeutic target identification.
    Keywords:  Acyl-homoserine lactones; Antimicrobial resistance; Extracellular polymeric substances; Persister cells; Quorum-sensing
    DOI:  https://doi.org/10.1016/j.meegid.2026.106028
  8. Chin Med J (Engl). 2026 Sep 18.
    Bacteriophages in humans: From discovery and mechanisms to therapeutic promise in combating disease.
    Xiaoming Yuan, Nengneng Li, Shengtao Zhu, Tao Zuo.
       ABSTRACT: Since the discovery of bacteriophages over a century ago, bacteriophages have evolved from fundamental biological models into promising therapeutic agents, especially in the era of antimicrobial resistance and in the treatment of human diseases. This article systematically reviews the key milestones in phage research and application at both international and Chinese fronts. It examines the evolving understanding of phage-bacterium interactions, which provides the development of targeted phage-based biocontrol and therapeutic strategies. Particular emphasis is placed on recent advances linking phages to human diseases, including their potential roles in gut microbiota modulation and chronic disease contexts. Despite promise, substantial challenges remain. The article concludes by discussing critical future directions, emphasizing the need for identifying key microbial targets in diseases, integrating phage therapy with emerging technologies to accelerate clinical translation, and exploring dietary phage interventions for disease prevention.
    Keywords:  Bacteriophages; Gut; Human disease; Microbiome; Phage therapy; Phageome
    DOI:  https://doi.org/10.1097/CM9.0000000000004296
  9. Front Microbiol. 2026 ;17 1838809
    Genomic and functional characterization of novel therapeutic lytic bacteriophages targeting multidrug-resistant Enterobacter cloacae.
    Mohammad S A Al-Obaidi, Mushtak T S Al-Ouqaili, Farah Al-Marzooq.
      The alarming rates at which extensively drug-resistant (XDR) and pandrug-resistant (PDR) Enterobacter cloacae in hospitals are increasing has begun to severely limit treatment options, and thus the urgency for alternative interventions, including bacteriophage therapy. The purpose of the study was to isolate and molecularly characterize phages that can infect E. cloacae, and, furthermore, to assess the antimicrobial efficacy of the four novel lytic bacteriophages (MMRP1, MMRP2, MMRP3, and MMRP4) against antimicrobial-resistant E. cloacae isolates and to evaluate their potential as alternative therapeutic strategies. These novel phages were characterized by plaque morphology, transmission electron microscopy (TEM), host range testing, thermal and chloroform stability assays, bacterial reduction assays, and whole-genome sequencing (WGS). Among 27 clinical isolates, MDR, XDR, and PDR phenotypes were observed in 20 (74.1%), six (22.2%), and one (3.7%) isolates, respectively. All four phages produced clear lytic plaques (0.5-3.0 mm) with titers reaching up to 6 × 1010 PFU/mL, and the phage cocktail lysed 81.4% (22 of 27 isolates) of clinical isolates with high host specificity. TEM revealed that all four E. cloacae-infecting phages (MMRP1, MMRP2, MMRP3, and MMRP4) belong to the class Caudoviricetes, exhibiting icosahedral capsids, tailed morphology, and double-stranded DNA genomes, consistent with current ICTV classification criteria. Whole genome sequencing and comparative phylogenetic analysis further resolved the taxonomic placement of these phages at the family level, positioning MMRP1 within the family Demerecviridae and MMRP4 within the family Straboviridae. All phages were stable from -20 to 40 °C and were unaffected by exposure to chloroform. Phage cocktail reduced bacterial OD₆₀₀ to ≤ 0.3 within 4 h in the bacterial reduction test. WGS revealed large circular dsDNA genomes of ~132 kbp (MMRP1) and ~149 kbp (MMRP4), GC content of 38%, and modular architectures encoding structural, lytic, and replication gene modules. The most striking and highlighted suggestion that in vitro evaluation of MMRP1 and MMRP4 are highly recommended to more deeper future experimental studies to combat MDR E. cloacae nosocomial infections supported by genomic foundation and eventually, the possibility to be suitable for phage-engineering applications in clinical settings.
    Keywords:  Enterobacter cloacae; bacteriophage; multidrug-resistant; phage therapy; whole genome sequencing
    DOI:  https://doi.org/10.3389/fmicb.2026.1838809
  10. Folia Biol (Praha). 2026 Sep 14.
    Engineered Bacteriophages in Cancer Immunotherapy: Emerging Concepts and Potential Integration with CAR-T Cell Therapy.
    Jehan Alrahimi.
      Due to antigen heterogeneity, restricted immune cell trafficking and an immunosuppressive, nutrient-restricted tumour microenvironment, solid tumours remain resistant to modern immunotherapies. Engineered bacteriophages offer a modular framework to overcome these obstacles: programmable virus-like particles with scalable production. Through genome engineering, capsid decoration with mammalian cell-targeting ligands, or hybrid AAV/phage systems, engineered bacteriophages can display tumour-associated antigens, enhance receptor-mediated uptake and deliver therapeutic payloads such as cytokines, chemokines and suicide genes without naturally infecting mammalian cells. These features support their use as vaccine platforms, immunological adjuvants and targeted gene-delivery vehicles. These may enable more precise, tumour-localized therapeutic intervention. Phages can engage innate immune pathways, including TLR9, TLR3/7/8, cGAS-STING and AIM2, promoting dendritic cell maturation and inflammatory mediators that may convert immunologically "cold" tumours into inflamed microenvironments. Their multivalent antigen display enhances B- and T-cell priming, while cDC1-mediated cross-presentation supports cytotoxic CD8+ T-cell responses and immunological memory. In CAR-T therapy, engineered phages may improve tumour homing through chemokine modulation, support persistence through local cytokine delivery, reduce antigen escape by presenting multiple tumour epitopes, and limit T-cell exhaustion through dominant-negative receptor strategies or local checkpoint blockade. This review summarizes engineering approaches, delivery systems, manufacturing, biodistribution, dosing, and safety issues, including immunogenicity, pre-existing anti-phage antibodies and horizontal gene transfer. It also distinguishes therapeutic engineered phage particles from phage display technologies used for molecular discovery. Despite encouraging results integrating modified bacteriophages with CAR-T cell therapy, the evidence remains mostly preclinical, indicating both substantial translational prospects and crucial obstacles for future clinical development.
    Keywords:  CAR-T cell therapy; CRISPR selection; adaptive immunity; cancer immunotherapy; innate immunity; phage engineering; phage therapy; tumour microenvironment
    DOI:  https://doi.org/10.14712/fb2026.0018
  11. Front Clin Diabetes Healthc. 2026 ;7 1833678
    Single-cell RNA sequencing in diabetic foot ulcers: pathogenesis, biomarkers, and translational potential.
    Shuhan Yang, Siqian Wang, Ruiyi Yang, Ke Xu, Xiaofeng Yang, Yifeng Zhao.
      Diabetic foot ulcer (DFU), a common diabetic complication driven by impaired angiogenesis, neuropathy and metabolic disorders, has complex pathogenesis and poses great challenges to clinical management. Single-cell RNA sequencing (scRNA-seq), an emerging transcriptomic technique, allows disease profiling at single-cell resolution. This review summarizes recent advances in scRNA-seq-based DFU research, revealing that JMJD3-mediated macrophage polarization failure and dysregulated IGF-1-SP1-CD248 pathway hinder wound repair, with MMP1, MMP3, MMP11, JMJD3 and HIF1A identified as valuable biomarkers and therapeutic targets. It highlights scRNA-seq's utility in unraveling pathogenic mechanisms, discovering therapeutic targets and biomarkers, and facilitating precision medicine, to provide new insights and research directions for DFU therapy.
    Keywords:  diabetic foot ulcer; extracellular matrix remodeling; macrophage polarization; single-cell sequencing; wound healing
    DOI:  https://doi.org/10.3389/fcdhc.2026.1833678
  12. J Res Pharm Pract. 2026 ;15(1): 17
    Healing or Harming? Navigating Resistance and Rationality in Diabetic Foot Ulcer Antibiotic Therapy: A Retrospective Observational Study.
    Maria Infant Majula Shifani Mahendran, Vinoj Gopalakrishnan, Vaijayanthi Saravanan.
      Diabetic foot ulcers (DFUs) represent a major complication in patients with diabetes mellitus, resulting in reduced quality of life, frequent hospitalizations, and increased healthcare costs. Our study analyzed the clinical records of 200 patients with DFU selected from a pool of medical records from a tertiary care hospital in India. Our study assessed patterns of drug prescription, determined pathogen profiles and antimicrobial susceptibility, evaluated economic burden, and identified the prevalence and severity of drug-drug interactions (DDIs) among patients with DFUs. Antibiotics were the most commonly prescribed drugs (18.5%) with the highest incidence of serious DDIs (28.5%). These results underscore the importance of optimizing antibiotic stewardship and rational prescribing practices to improve clinical outcomes.
    Keywords:  Antibiotic use; diabetes foot ulcer; diabetes mellitus; drug–drug interactions
    DOI:  https://doi.org/10.4103/jrpp.jrpp_81_25
  13. Einstein (Sao Paulo). 2026 ;pii: S1679-45082026000901404. [Epub ahead of print]24(spe3): eRW2369
    Bacteria-induced immunity: from homeostasis to immune subversion in periodontitis.
    Vallentine Louzada Miranda, Mel de Araujo Teixeira, João Gabriel Silva Souza, Letícia Mello Bezinelli, Nídia Cristina Castro Dos Santos.
      This review synthesizes current evidence on host immune responses to bacteria, their roles in the development and progression of periodontitis, and emerging immunomodulatory therapeutic strategies designed to restore periodontal homeostasis. Periodontitis develops through interactions between a dysbiotic bacterial community that disrupts host-microbe homeostasis and a chronic, maladaptive interaction with the host immune system. Key immune subversion microorganisms such as Porphyromonas gingivalis trigger inflammation while subverting immune surveillance by evading complement-mediated clearance and impairing neutrophil function. This dual behavior creates a biological paradox: bacteria induce inflammation to obtain nutrients while simultaneously suppressing effective antimicrobial activity, thereby perpetuating chronic, tissue-destructive immune activation. The osteoimmune response, particularly the Th17/IL-17 axis, is a central pathway linking microbial dysbiosis to persistent inflammation and alveolar bone resorption. These findings suggest that successful periodontal therapy must extend beyond mechanical biofilm removal by addressing underlying immune dysregulation. Potential adjunctive strategies for modulating this response include specialized pro-resolving mediators, complement inhibitors such as Cp40, and selected probiotics with immunoregulatory properties. Collectively, these approaches are intended to restore immune balance, enhance resolution of inflammation, and promote periodontal tissue repair. Current evidence demonstrates that periodontitis is not solely a microbial infection but also involves dysregulated host immunity. Clarifying how bacteria manipulate immune pathways may facilitate the development of therapies that complement bacterial control by targeting the inflammatory mechanisms underlying tissue destruction. Immunomodulatory interventions therefore represent promising candidates for promoting sustained periodontal stability and inflammatory resolution.
    DOI:  https://doi.org/10.31744/einstein_journal/2026RW2369
  14. Front Cell Infect Microbiol. 2026 ;16 1917870
    Absolute quantification by mouthwash testing screens severe periodontitis and tracks species-specific microbial response to periodontal therapy.
    Je-Hyun Eom, Mu-Yeol Cho, Ji-Won Kim, Yunwoo Kim, Jeehyun No, Jiyoung Hwang, Seokwon Kim, Dahye Lee, Hanseung Baek, Bae-Kyung Kim, Young-Youn Kim, Soo-Bok Her, Dong-Yub Ko, Inseong Hwang, Hye-Sung Kim.
       Background: Non-invasive molecular tools that can both screen for severe periodontitis and quantify treatment-associated pathogen changes remain an unmet need. We evaluated a non-invasive multiplex quantitative polymerase chain reaction (qPCR) mouthwash panel providing absolute colony-forming-unit (CFU) quantification of five periodontal pathogens (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Prevotella intermedia, Fusobacterium nucleatum), and asked whether a single test can both screen for severe disease and track each patient's species-level treatment response.
    Methods: Treatment-response monitoring was assessed in a real-world retrospective cohort (349 patients, 703 visits; 235 paired pre/post-treatment samples) using paired Wilcoxon signed-rank tests and Jonckheere-Terpstra trend tests across baseline stage. Screening performance was independently evaluated in a prospective cross-sectional cohort (n=87; 31 healthy, 56 Stage III/IV) with leave-one-out cross-validation (LOOCV) and a pre-specified sensitivity analysis.
    Results: For screening, LOOCV AUC was 0.96 for P. gingivalis and 0.97 for the combined panel, preserved under inclusion of antibiotic- and treatment-exposed subjects. Beyond screening, the panel resolved each patient's species-level response to non-surgical therapy: all five species decreased significantly, with median within-patient reductions of -0.37 to -0.72 log10 CFU (paired Wilcoxon, all p<0.001) and reduction magnitude scaling with baseline severity. This response was strongly species-specific and clinically informative at the individual level: In the implant-bearing high-baseline-burden subgroup, post-treatment F. nucleatum reached or fell below the Healthy reference median in 61% of evaluable patients, whereas P. gingivalis reached it in only 5% and remained approximately 500-fold above the Healthy reference at the median final visit, identifying residual keystone-pathogen burden not captured by clinical or radiographic assessment.
    Conclusion: In this two-cohort evaluation, a single non-invasive mouthwash qPCR test provided two linked clinical outputs: high-accuracy screening for severe periodontitis and quantitative individual-level tracking of species-specific microbial response to therapy. These findings are preliminary, derive from a single-center screening cohort and a retrospective monitoring cohort, and require external validation before clinical deployment. By placing pathogen loads on the same absolute CFU scale, the assay supports both cross-sectional disease detection and longitudinal residual-burden monitoring as an adjunct to the 2018 AAP/EFP framework. Clinical Research Information Service (CRIS) registration: KCT0011511 (https://cris.nih.go.kr).
    Keywords:  Porphyromonas gingivalis; absolute quantification; mouthwash; periodontal microbiome; periodontitis; quantitative real-time PCR; treatment monitoring
    DOI:  https://doi.org/10.3389/fcimb.2026.1917870
  15. Front Immunol. 2026 ;17 1884094
    Autoimmune disease-associated pathobionts: mechanisms and therapeutic potential of phage-based approaches.
    Kentaro Kuzuya, Yuichi Maeda, Kenji Funakoshi, Yumiko Mizuno, Kosuke Fujimoto.
      The gut microbiota is a critical regulator of systemic immune homeostasis; accumulating evidence implicates specific commensal bacteria, termed "pathobionts," in autoimmune disease pathogenesis. However, the definition of pathobionts remains context-dependent, as their effects are influenced by host genetics and host-microbe interactions. In this review, we summarize representative pathobionts supported by functional evidence in selected extraintestinal autoimmune diseases and discuss how these mechanisms may inform phage-based microbiome-targeted interventions. Mechanistically, pathobionts contribute to autoimmune disease through multiple pathways, including molecular mimicry, induction of intestinal T helper 17 and T follicular helper cell responses, disruption of regulatory T cell homeostasis, intestinal barrier dysfunction, and bacterial translocation from the gut to extraintestinal sites. These processes highlight the central role of gut-associated lymphoid tissue in initiating systemic autoimmunity, and targeting disease-associated microbes represents a promising therapeutic strategy. Whole-phage therapy, which enables highly specific bacterial elimination, has shown efficacy in preclinical immune-mediated disease models, but may be affected by variable in vivo replication, bacterial receptor-mediated resistance, anti-phage immune responses, and ecological effects on the resident microbiome. Phage-derived enzymes that lyse bacterial cell walls, such as endolysins, represent a complementary therapeutic modality that specifically targets bacterial peptidoglycan through cell wall-binding and catalytic domains. Collectively, these findings support the concept that pathobiont-targeted interventions, particularly phage-based strategies, may provide microbiome-directed, immunosuppression-sparing therapeutic approaches for selected patient subsets.
    Keywords:  autoimmune diseases; bacteriophage; endolysin; microbiota; pathobiont
    DOI:  https://doi.org/10.3389/fimmu.2026.1884094
  16. PLoS One. 2026 ;21(9): e0356919
    Substrate morphology modulates bacteriophage mobility and alters bactericidal potency.
    Haoyu Wang, Oluyemi Olatunji Awolusi, Saravana Kumar Jaganathan, Jing Lyu, Chaozong Liu, Nick Tucker, Bukola Adenike Onarinde.
      Bacteriophages (phages) are regaining attention as alternatives to antibiotics in the antimicrobial resistance crisis. Although successful cases are widely reported, the influence of physical, abiotic substrate morphology on phage performance remains largely unexamined, despite morphology being an intrinsic topographical feature present at many infection and decontamination sites, such as granular chronic wound beds or porous bone-implant interfaces. In this study, smooth, rough, and porous substrates were physically engineered to investigate the effects of abiotic substrate morphology on phage potency. Profiler and SEM analyses confirmed three distinct morphologies spanning several orders of magnitude in surface roughness. Phage K exhibited a clear hierarchy of bactericidal activity across these morphologies, with the highest activity on smooth substrates, reduced activity on rough substrates, and the lowest activity on porous architectures. Histological analysis and COMSOL simulations revealed that increasing morphological complexity elevates tortuosity and reduces phage accessibility and the probability of encountering pathogens. Together, these findings establish substrate morphology as a critical determinant of phage kinetics and bactericidal potency, relevant both to surface decontamination and, cautiously, to real infection sites such as wound beds and implant-tissue interfaces that inherently possess complex microarchitectures. Incorporating substrate morphology into the design of phage-based applications may improve the predictive accuracy of dosing, interval design, and clinical translation, and deepen understanding of the underlying pharmacology.
    DOI:  https://doi.org/10.1371/journal.pone.0356919
  17. J Cancer Res Clin Oncol. 2026 Sep 17. pii: 180. [Epub ahead of print]152(9):
    Retraction Note: Phage therapy and the microbiome in hematologic malignancies: opportunities, mechanisms, and early evidence.
    Juanwen Zhang, Jin Liu, Alireza Bayani.
      
    DOI:  https://doi.org/10.1007/s00432-026-06623-5
  18. Oral Dis. 2026 Sep 15.
    The Oral Microbiome-Inflammaging Axis in Elderly Periodontitis: Emerging Immunopathogenic and Systemic Mechanisms.
    Jabborova Feruza, Masharipov Otajon, Mukimov Shaxobiddin, Afakova Mamura, Kubaev Aziz, Khakimova Nargiza, Zebiniso Alimova.
       BACKGROUND: Periodontitis prevalence increases with age, yet "elderly periodontitis" is not merely cumulative plaque exposure. Aging remodels mucosal immunity, elevates chronic inflammation, and promotes senescent cell accumulation with pro-inflammatory secretory phenotypes.
    OBJECTIVE: To critically evaluate the self-reinforcing oral microbiome-inflammaging axis in elderly periodontitis.
    METHODS: Narrative synthesis of mechanistic studies, human cohorts, and preclinical models investigating interactions between oral microbial ecology, immunosenescence, cellular senescence, and inflammaging.
    RESULTS: Dysbiotic biofilms deliver persistent pressure interpreted by aged immune-stromal networks with heightened inflammatory gain. Mechanistic studies implicate aging-sensitive TLR9 sensing, age-amplified inflammasome-linked macrophage responses to P. gingivalis, and senescent niches that potentiate inflammation. Microbes directly induce senescence programs, including epithelial senescence and exosome-mediated paracrine immune senescence. Systemically, periodontitis induces multi-organ frailty-like phenotypes, neuroinflammatory changes, persistent gut dysbiosis, and altered metabolomes despite local therapy.
    CONCLUSION: Elderly periodontitis represents a geroscience-relevant disorder where dysbiosis and biological aging jointly establish a self-sustaining inflammatory ecosystem. Priority gaps include longitudinal elderly cohorts integrating microbiome function with senescence markers and stratified trials combining biofilm control with host modulation.
    Keywords:  dysbiosis; immunosenescence; inflammaging; oral–systemic axis; senile periodontitis
    DOI:  https://doi.org/10.1111/odi.70493
  19. Front Cell Infect Microbiol. 2026 ;16 1927507
    More than an infection: the ecological puzzle of recurrent urinary tract infections.
    Layla Musleh, Marco Montilli, Maria Grazia Ammendolia, Alessandro Sciarra, Anna Riccioli, Linda Maurizi, Catia Longhi.
      Recurrent urinary tract infections (rUTIs) represent one of the most common infectious conditions worldwide, yet their pathophysiology extends far beyond repeated episodes of acute bacterial cystitis. Increasing evidence indicates that recurrence may arise through overlapping mechanisms including reinfection from intestinal or periurethral reservoirs, intracellular bacterial persistence, microbial dysbiosis, impaired mucosal immunity and chronic inflammatory remodelling of the bladder microenvironment. Current diagnostic frameworks remain largely based on symptom-based definitions and standard urine culture, approaches that incompletely capture the biological complexity of recurrent disease. This limitation is evident even at the definitional level, where clinically pragmatic categories often fail to reflect the heterogeneous mechanisms underlying recurrence. Advances in expanded urine culture techniques, metagenomics and metabolomics have reshaped the understanding of the urinary tract as a dynamic ecological system interconnected with vaginal, intestinal and prostatic microbial compartments. These approaches have identified diverse microbial communities, virulence-associated functional profiles and host-microbe interactions linked to recurrence-prone phenotypes. Significant challenges continue to persist in elucidating the biological mechanisms driving recurrence. Addressing these gaps is essential to improve disease characterization and support the development of more effective diagnostic and therapeutic approaches.
    Keywords:  antimicrobial therapy; host microbe interactions; microbial persistence; mucosal immunity; recurrent urinary tract infections; urinary microbiome
    DOI:  https://doi.org/10.3389/fcimb.2026.1927507
  20. Front Pharmacol. 2026 ;17 1855791
    Shengji ointment accelerates diabetic foot ulcer wound healing by regulating inflammatory microenvironment.
    Rui Dai, Jing Guo, Jinpeng Jing, YunSha Zhang, HongBin Liu, Zhaohui Zhang, Chaojun Zhu.
       Background: Diabetic foot ulcers (DFUs) represent a significant clinical challenge due to their high morbidity, infection risk, and poor healing rates. Emerging evidence highlights the therapeutic potential of Traditional Chinese Medicine in wound management. This study investigates the efficacy of Shengji Ointment (SJ)-a multi-herb formulation-in human subjects with DFUs and a diabetic rat model, specifically elucidating its modulation of the wound inflammatory microenvironment.
    Methods: The lyophilized powder of the SJ extract was analyzed using UPLC-MS/MS to profile its chemical constituents. A single-center, prospective, randomized, controlled clinical study was conducted in patients with Wagner Grade 3 DFUs. A diabetic wound rat model was established, and proinflammatory cytokine and growth factor levels in granulation tissue were quantified at multiple time points.
    Results: UPLC-MS/MS identified 3,552 distinct UPLC-MS/MS identified 3,552 distinct compounds in the SJ extract, predominantly flavonoids and alkaloids in the SJ extract, predominantly flavonoids and alkaloids; 10 high-abundance compounds were selected (5 at MSI Level 1). The clinical study demonstrated that SJ significantly accelerated DFU wound healing. The animal study revealed that SJ promotes wound healing by modulating the wound microenvironment.
    Conclusions: This study demonstrated that Shengji Ointment (SJ) could inhibit excessive inflammation, promote angiogenesis and vascular maturation, and thereby markedly accelerate diabetic wound healing in both clinical settings and rat models. Such therapeutic effects may be associated with the DLL4/Notch1-VEGF/VEGFR2 signaling pathway.
    Keywords:  Shengji ointment; Traditional Chinese Medicine; diabetic foot ulcers; inflammatory microenvironment; wound healing
    DOI:  https://doi.org/10.3389/fphar.2026.1855791
  21. Pediatr Pulmonol. 2026 Sep;61(9): e71829
    The Cost of Control: Financial and Administrative Burdens of Limited Distribution Network Changes in Cystic Fibrosis.
    Brittany A Wright, Cameron J McKinzie, Charissa W Kam, Casey R Tak, Lynnsey M Knockel, Julie Langhorst, Rebecca S Pettit, Lynda Roe, Billie Simonson, Hilary Vogt, Nicole Willer, David C Young.
       BACKGROUND: The clinical impact of pharmacists and pharmacy technicians on the care of people with cystic fibrosis (pwCF) has been well documented within the literature, including medication access, reduction of hospitalizations, and consolidation of pharmaceutical delivery for pwCF with complex medication regimens. However, challenges related to access and affordability have become increasingly complex, increasing the administrative burden placed upon these members of the multidisciplinary CF care team. The goal of this study was to quantify the time pharmacists and pharmacy technicians at CF Foundation-accredited care centers (CFACC) spent triaging and resolving errors, categorize the types of interventions required, and tabulate the financial burden for pwCF averted through these interventions.
    METHODS: This study was a retrospective review of pharmacy team members' interactions following a change in limited distribution network of cystic fibrosis transmembrane conductance regulator modulators (CFTRm) over a 4-month period of time. Each site received institutional review board exemption. Measures were characterized using descriptive statistics and were analyzed in SAS v9.4 (Cary, NC). Collected data were extrapolated to be nationally representative based on the 2023 CFF Patient Registry report.
    RESULTS: Six CFACC and 1781 pwCF were included in this review. Of these pwCF, 216 required additional interventions following a required change in the dispensing pharmacy for their CFTRm. Collectively, 201.5 h were spent on resolution of issues during the study period with interventions successfully averting a financial burden to pwCF of $226,094.73. Extrapolations of time and financial burden were estimated to be 3700 h and over $4.2 million, respectively.
    CONCLUSIONS: Medication access and affordability continue to present significant barriers for pwCF. We aim to highlight the critical services provided by clinical pharmacy teams at CFACC as well as their integrated health-system specialty pharmacies, and the vital role they play in improving outcomes and providing cost-effective care for pwCF.
    Keywords:  CFTR modulators; medication access and affordability; pharmacy services
    DOI:  https://doi.org/10.1002/ppul.71829
  22. J Rehabil Assist Technol Eng. 2026 Jan-Dec;13:13 20556683261488849
    Design and evaluation of a custom contoured pneumatic insole for active plantar pressure offloading.
    Veysel Erel, Allison Palomino, Yi-Ting Tzen, Lawrance A Lavery, Dane K Wukich, Muthu B J Wijesundara.
       Introduction: Diabetic foot ulcers (DFUs) are a major cause of morbidity, amputation, and mortality in people with diabetes. Excessive and repetitive plantar loading contributes significantly, and although therapeutic footwear is widely prescribed, its effectiveness varies. Custom insoles improve pressure redistribution but do not address repetitive loading. Emerging active offloading technologies offer targeted relief, yet fully custom-contoured active systems remain untested.
    Methods: This study compared a custom-contoured active insole with a non-custom flat active insole under static and dynamic conditions in an individual without DFU risk. Both designs used seven pneumatically actuated air cells and were tested at 1.5 and 2.0 psi. Pressures were measured using a high-resolution in-shoe sensor and quantified using maximum mean pressure (MMP) and peak pressure (PP).
    Results: The custom insole consistently produced lower pressures, with substantial reductions in midfoot and heel regions and frequent MMP and PP decreases exceeding 45 percent during walking.
    Conclusion: Integrating patient-specific geometry with active pneumatic offloading enhances plantar pressure redistribution and may help prevent DFUs.
    Keywords:  active offloading; custom insole; diabetic foot ulcers; lower extremity wounds; plantar pressure; shoe insole
    DOI:  https://doi.org/10.1177/20556683261488849
  23. Ther Adv Infect Dis. 2026 Jan-Dec;13:13 20499361261452940
    Bacterial profile and antimicrobial resistance patterns of infected diabetic foot ulcers in low- and middle-income countries: a systematic review and meta‑analysis.
    Aaron Awere-Duodu, Frederick Kungu, Yacoba Atiase, Eric S Donkor.
       Background: Diabetic foot ulcers (DFUs) are often polymicrobial infections, necessitating antibiotic therapy. However, the high prevalence of antibiotic misuse and the growing issue of antibiotic resistance in low- and middle-income countries (LMICs) exacerbate the challenges in managing these ulcers, contributing to the risk of lower-limb amputations.
    Objectives: This systematic review reported the bacterial profile and antibiotic resistance patterns associated with DFUs in LMICs.
    Design: A systematic review and meta-analysis.
    Data sources and methods: A comprehensive search was conducted in PubMed, SCOPUS, and Web of Science to retrieve relevant articles, which were screened according to predefined selection criteria. Publication bias was assessed with a funnel plot and Egger's regression test. A meta-analysis was conducted in RStudio version 4.5.2, using the random-effects model. Meta-regression and sensitivity analysis were conducted to assess the sources of heterogeneity and robustness of the included studies, respectively.
    Results: The most frequently isolated bacteria were Staphylococcus aureus (22.64%), Escherichia coli (12.37%), Pseudomonas aeruginosa (8.49%), Klebsiella pneumoniae (5.19%), P. mirabilis (4.61%), and Coagulase-negative Staphylococci (4.86%). The prevalence of key antibiotic-resistant bacteria was as follows: Methicillin-resistant S. aureus (38.65%), Extended-spectrum beta-lactamase (ESBL)-producing E. coli (50.74%), and ESBL-producing K. pneumoniae (41.54%). S. aureus demonstrated the highest resistance to penicillin (96.87% (93.30; 99.32)), azithromycin (76.42% (64.54; 86.65)), and cefoxitin (68.19% (46.83; 86.67)). E. coli showed the highest resistance to ampicillin (86.60% (77.14; 94.18)) and cotrimoxazole (69.27% (57.35; 80.18)).
    Conclusion: Pathogenic bacteria isolated from DFUs in LMICs exhibit high rates of antibiotic and multidrug resistance. Alternative therapies, such as phage therapy, should be explored as potential treatments for DFUs to mitigate the impact of antibiotic resistance and decrease the rate of diabetes-related amputations.
    Trial registration: Open Science Framework (OSF) registry, available at https://doi.org/10.17605/OSF.IO/DPX9F.
    Keywords:  LMICs; antibiotic resistance; bacterial profile; diabetes mellitus; diabetic foot ulcer
    DOI:  https://doi.org/10.1177/20499361261452940
  24. Comp Biochem Physiol Part D Genomics Proteomics. 2026 Sep 13. pii: S1744-117X(26)00283-2. [Epub ahead of print]61 102024
    From dysbiosis to resilience: Microbiome engineering for sustainable shrimp aquaculture.
    Safdar Imran, Yasmeen Junejo, Hafiz Ishfaq Ahmad, Mehmet Ozaslan, Muhammad Safdar.
      The intensification of shrimp aquaculture has increased exposure to disease, environmental perturbations, and antimicrobial pressure, making microbial stability increasingly relevant to sustainable production. Microbiome stability-encompassing resistance to disturbance and resilience of functional recovery-provides an ecological framework for understanding how shrimp and culture-environment microbial communities respond to intensive farming. This review examines the transition from microbial homeostasis to dysbiosis and evaluates how microbiome engineering could redirect disrupted communities towards resilient states. Evidence is integrated across the intestine, hepatopancreas, rearing water, sediment and biofloc to assess how host genetics, ontogeny, diet, culture conditions, antibiotics and pollutants shape microbiome assembly and destabilization. Disease-associated changes in acute hepatopancreatic necrosis disease, white faeces syndrome, Enterocytozoon hepatopenaei infection, and white spot syndrome virus infection are critically evaluated, with explicit separation of associations, pathogen-induced dysbiosis, and community-level causality. Established and emerging interventions-including probiotics, prebiotics, synbiotics, functional diets, biofloc management, phages, postbiotics, microbiota transplantation and synthetic microbial communities-are assessed according to their capacity to modify microbial function, persistence and recovery rather than taxonomic change alone. We further examine how multi-omics, microbiome-informed breeding, and environmental monitoring could support biomarker development, predictive decision support and context-specific intervention. We argue that progress requires a shift from taxonomic description to function-guided engineering, from endpoint comparisons to direct measurement of resilience, and from laboratory efficacy to reproducible farm-scale validation. Overall, microbiome management may contribute to more disease-resilient and sustainable shrimp production, provided that its effectiveness can be validated under commercial farming conditions.
    Keywords:  Dysbiosis; Microbial resilience; Microbiome engineering; Multi-omics; Penaeus vannamei; Precision aquaculture; Shrimp microbiome
    DOI:  https://doi.org/10.1016/j.cbd.2026.102024
  25. J Alzheimers Dis. 2026 Sep 17. 13872877261488806
    Periodontal disease and Alzheimer's disease: A systematic review.
    María Del Carmen Alcaide-Prados, Gerardo Gómez-Moreno, Ignacio Osoitz Leizaola-Cardesa, Gerardo Moreu, Antonio Roa-López, Antonio Aguilar-Salvatierra.
      BackgroundPeriodontitis is a host-mediated inflammatory disease of microbial origin that results in the loss of periodontal attachment. Its effects are not limited to the oral cavity, as association with systemic diseases, including Alzheimer's disease (AD), has been widely reported.ObjectiveTo evaluate the evidence regarding the potential relationship between periodontitis and AD through a systematic review.MethodsA bibliographic search was conducted in PubMed, Scopus, and WOS. Studies published within the last five years evaluating the biological association between both diseases were selected. The methodological quality and risk of bias of the included studies were assessed using the NOS and ROBINS-I tool, according to the study design.ResultsEleven studies were included. Eight studies analyzed biological samples obtained from brain tissue, blood/serum, saliva, gingival crevicular fluid, and cerebrospinal fluid. Patients with AD exhibited higher levels of periodontopathogenic bacteria, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia, and an association between bacterial load and systemic inflammatory markers. Although most studies reported an association between periodontitis and AD, the findings were not consistent across studies, as some failed to identify statistically significant differences. Periodontal treatment was associated with a reduction in the AD Score, a neuroimaging surrogate marker of preclinical AD, whereas no effect was observed on brain age gap.ConclusionsEvidence suggests a possible association between periodontitis and AD through inflammatory and neurodegenerative mechanisms. Methodological limitations and study heterogeneity preclude establishing causality, underscoring the need for longitudinal studies and alternative methodological approaches.
    Keywords:  Alzheimer's disease; amyloid-beta peptides; cognitive dysfunction; microbiota; periodontitis; tau proteins
    DOI:  https://doi.org/10.1177/13872877261488806
  26. Health Sci Rep. 2026 Sep;9(9): e72927
    Causes and Contributing Factors of In-Hospital and Post-Discharge Mortality Among Patients With Severe Acute Respiratory Infection in Low- and Middle-Income Countries: A Scoping Review.
    Md Ariful Islam, Holly Seale, Md Saiful Islam, Saju Bhuiya, Md Zakiul Hassan, Quazi Fayeza Sultana, Fahmida Chowdhury, Abrar Ahmad Chughtai.
       Background and Aims: Severe acute respiratory infections (SARI) remain a major cause of global morbidity and mortality, with a disproportionate burden in low- and middle-income countries (LMICs). Although in-hospital mortality is frequently reported, deaths occurring after hospital discharge remain poorly documented. We aimed to synthesise the available evidence on the causes and contributing factors of in-hospital and post-discharge mortality among patients hospitalised with SARI in LMICs.
    Methods: We conducted a scoping review following the Arksey and O'Malley framework and PRISMA-ScR guidelines. PubMed, Web of Science, Scopus, and CINAHL were searched for studies published between January 2000 and October 2025 that reported in-hospital and/or post-discharge mortality among patients with SARI in LMICs. Findings were synthesised narratively to describe factors associated with in-hospital and post-discharge mortality, as well as reported causes of death.
    Results: Twenty-nine studies from 13 LMICs met the inclusion criteria. All reported in-hospital mortality (range: 0.4%-39.3%), while four reported post-discharge mortality (range: 0.6%-5.7%). Thirteen studies examined factors associated with mortality. In-hospital mortality was associated with older age, male sex, comorbidities, markers of severe clinical presentation, specific respiratory pathogens, and delayed healthcare seeking. Only one study specifically evaluated factors associated with post-discharge mortality, identifying respiratory difficulty, underlying heart disease, and longer hospital stay among children, and chronic obstructive pulmonary disease and intensive care unit admission among adults as risk factors. Pathogen-specific causes of in-hospital death were reported in a single study, and no study reported definitive causes of post-discharge mortality.
    Conclusion: Evidence on SARI-associated mortality in LMICs is largely confined to in-hospital outcomes, with limited assessment of post-discharge mortality or causes of death. Standardised post-discharge follow-up and systematic cause-of-death reporting are needed to inform clinical care, strengthen surveillance, and support targeted interventions to reduce preventable SARI-associated mortality in LMICs.
    Keywords:  LMIC; causes; factors; mortality; scoping review; severe acute respiratory infection
    DOI:  https://doi.org/10.1002/hsr2.72927
  27. Exp Ther Med. 2026 Oct;32(4): 287
    Gut microbiome dynamics in acute infectious diarrhea: A conceptual framework from acute dysbiosis toward precision restoration (Review).
    Cong Yuan, Jiale Tong, Weiwei Qian, Qian He.
      Acute diarrhea affects >1 billion individuals annually, imposing a major health and economic burden worldwide. Although the involvement of the gut microbiota is increasingly acknowledged, the dynamics of microbiota disruption, recovery and related therapeutic opportunities remain poorly integrated. The present review proposed a conceptual framework that synthesizes current understanding of pathogen-driven structural and functional alterations of the microbiota, the staged ecological succession during convalescence (including risks of incomplete restitution) and emerging microbiota-based interventions, ranging from probiotics to phage therapy. The present review further highlighted the potential of artificial-intelligence-driven multi-omics integration, while mapping the distance between current evidence and future precision-medicine goals. Evidence-based interventions were explicitly distinguished from investigational strategies, and microbiota-derived diagnostic biomarkers were discussed as a promising research direction rather than ready-to-deploy clinical tools. Finally, the present review provided evidence-based recommendations to bridge ecological principles with bedside practice, framing acute infectious diarrhea as a severe but often reversible ecological perturbation (an acute dysbiosis) that reveals individual ecological vulnerability and offers a diagnostic window for risk stratification. The present review is intended as a conceptual and evidence-synthesis framework rather than a clinical practice guideline.
    Keywords:  acute diarrhea; diagnostic biomarker; gut microbiota; multi-omics; pathophysiology; therapeutic strategy
    DOI:  https://doi.org/10.3892/etm.2026.13282
  28. Adv Skin Wound Care. 2026 Oct 01. 39(9): 457-461
    Managing Complex Wounds After Treatment Failure: Patterns Identified in an Advanced Wound Healing Center.
    Lisa Draghi, Frank L Ross.
      Chronic wounds remain a significant clinical challenge despite advances in dressings, biologics, and adjunctive therapies. Patients referred to advanced wound centers following unsuccessful treatment often demonstrate recurring and potentially correctable factors that contribute to delayed healing. Drawing upon observations from a quaternary referral wound center, this article focuses on recurring and potentially correctable factors encountered during evaluation of wounds that have failed to progress despite prior care. Although these patterns are neither novel nor unexpected, they continue to recur despite well-established wound care principles and treatment guidelines. This article highlights common pitfalls identified in patients referred for advanced wound care evaluation. Commonly encountered issues include inadequate implementation of compression therapy and lower extremity elevation, ineffective offloading in diabetic foot ulcers, limited attention to patient adherence and behavioral factors, and incomplete evaluation of underlying contributors to wound chronicity. Additional patterns include continued use of outdated or nonevidence-based topical agents, misapplication of debridement principles (particularly removal of stable eschar), and incomplete evaluation of underlying pathophysiology such as vascular insufficiency. Patients are frequently referred after undergoing advanced interventions, including hyperbaric oxygen therapy and grafting procedures, before optimization of fundamental wound care principles. In these settings, suboptimal patient selection and sequencing of therapy, particularly in the presence of uncontrolled edema or inadequate offloading, may contribute to prolonged treatment without clinical benefit. These observations highlight recurring gaps between recommended care and real-world execution. Recognition of these recurring pitfalls may improve wound healing outcomes, promote more effective use of advanced therapies, and reduce the need for escalation of care.
    Keywords:  chronic wounds; compression; diabetic foot ulcer; edema; pitfalls; wound healing
    DOI:  https://doi.org/10.1097/ASW.0000000000000527
  29. Microbiol Spectr. 2026 Sep 14. e0155026
    Paired oral clinical specimens reveal the underlying ecology supporting the emergence of inflammophilic microbiome communities.
    Madeline Krieger, Kristopher A Kerns, Elizabeth A Palmer, Jeffrey S McLean, Jens Kreth, Galip Gürkan Yardımcı, Justin L Merritt.
      Across human mucosal sites, dysbiotic inflammatory diseases are characterized by compositional shifts in the resident microbiota, in which commensal-dominated communities give way to pathobiont-enriched communities where "inflammophilic" species often predominate. Effective treatments for these complex polymicrobial infections remain limited, in part, because the ecological mechanisms driving their emergence and persistence are still poorly understood. To address this gap, we analyzed a unique cohort of pediatric patient-matched, disease-free dental plaque and odontogenic abscess specimens, providing a clinically relevant model to examine microbiome transitions from commensal to inflammophilic states. Using complementary community ecology modeling approaches and inferred metagenomic analyses, we identified microbial taxa and functional programs associated with inflammatory selective pressure and dysbiotic community emergence. Dental plaque communities are characterized by anabolic metabolic processes and carbohydrate-derived ATP generation, whereas abscess microbiomes are highly biased for catabolic metabolism, amino acid-derived ATP generation, and antimicrobial resistance. The results suggest that abscess communities are much less reliant upon interspecies metabolic complementation compared to dental plaque communities, which would imply an obligate dependence upon host inflammatory responses to provide the key metabolites required for growth. These findings support a model in which an inflammophilic community ecology is largely the net result of a combination of enhanced resistance to innate immunity and compatibility with the inflammatory nutrient environment. By defining the metabolic requirements and selective pressures governing these dysbiotic transitions, it may be possible to suppress inflammatory dysbiotic diseases using ecologically focused therapeutic strategies that exploit the limited biosynthetic capacity of commensal depleted inflammophilic communities.IMPORTANCEDysbiotic inflammatory diseases are frequently sustained by complex microbial community interactions, but the ecological processes involved remain poorly understood. In this study, we leveraged pediatric patient-matched, disease-free dental plaque and odontogenic abscess clinical specimens to examine how oral microbial communities shift from health-associated to inflammation-associated states. We found that abscess microbiomes are enriched for features consistent with adaptation to inflammatory environments, including antimicrobial resistance, catabolic metabolism, and utilization of host-derived nutrients. These findings support a model in which host inflammation functions as a selective ecological pressure, favoring the establishment of metabolically specialized, inflammophilic microbial communities. By defining the ecological and functional features that distinguish abscess-associated communities from disease-free plaque microbiota, this work provides a framework for understanding inflammatory dysbiosis and for developing ecological strategies to disrupt pathobiont-enriched communities while promoting the restoration of stable, health-associated microbiota.
    Keywords:  microbiome; odontogenic abscess; oral dysbiosis; oral microbiome
    DOI:  https://doi.org/10.1128/spectrum.01550-26
  30. FEMS Microbiol Rev. 2026 Sep 18. pii: fuag048. [Epub ahead of print]
    From colonisation to immune evasion: a synthesis of the interaction strategies that drive Staphylococcus aureus infection.
    Guangqiang Jia, Kewei Chen, Haijiao Lin, Xin Zhao.
      Staphylococcus aureus (S. aureus) remains a major human and veterinary pathogen, driven by multiple virulence processes, including toxin activity, biofilm formation, metabolic adaptation, regulatory networks, antimicrobial resistance, strain-specific traits. Many of these processes involve host-pathogen protein-protein interactions (PPIs). This review focuses on PPIs as a major mechanistic layer that links adhesion, invasion and immune evasion across infection stages. We synthesise available evidence to explain how selected PPIs support the transition from carriage to invasive disease. We first compare surface adhesins that use distinct binding architectures, including Dock, Lock and Latch, the Collagen Hug and the tandem β-zipper, to achieve force-resilient attachment under physiological shear. We then organise immune-evasion PPIs along the chronology of host defence, from early sensing and antimicrobial barriers to phagocyte recruitment, complement and opsonisation, intraphagosomal killing and adaptive immunity. This staged view highlights how mechanoadaptive anchoring, redundancy and multifunctionality can contribute to robust infection phenotypes and suggests therapeutic opportunities involving allosteric modulation, decoy-based restoration of host pathways and multi-target biologics.
    Keywords:   Staphylococcus aureus ; anti-virulence therapy; bacterial adhesion and invasion; immune evasion; mechano-adaptation; protein–protein interactions
    DOI:  https://doi.org/10.1093/femsre/fuag048
  31. PLoS Pathog. 2026 Sep;22(9): e1014574
    Polymicrobial-driven NLRP6 inflammasome regulates IL-1β production and alveolar bone loss in a murine model of periodontitis.
    Sarah Metcalfe, Rajendra P Settem, Edwin J Ovalle, Michelle Panasiewicz, Alejandro Escobar, Jason G Kay.
      Periodontal disease is a chronic inflammatory condition that develops in response to oral microbiome dysbiosis and host-microbiome immune response dysregulation. The innate immune system plays a major role in the development and persistence of disease, in part by producing inflammatory cytokines. One of the major cytokines implicated in disease is interleukin-1β (IL-1β), which requires inflammasome activation. Much of the oral microbiome, including Streptococci, which are otherwise considered commensal, is required for the full development of periodontal disease. We have previously reported that inflammatory-activated macrophages and neutrophils counterintuitively allow survival of internalized Streptococcus gordonii over non-activated phagocytes. This internal bacterial survival leads to inflammasome activation via the cytoplasmic activator NLRP6, but not NLRP3, and subsequent increases in IL-1β release. Here, we test and find that the keystone pathogen Porphyromonas gingivalis can activate macrophages in a manner that allows for increased S. gordonii survival and IL-1β production above levels when P. gingivalis interacts with macrophages alone. We also use the mouse ligature-induced periodontal disease model to test the importance of NLRP6 in disease development. We found mice lacking NLRP6 had significantly reduced bone loss, IL-1β, and neutrophil infiltration following disease induced by P. gingivalis when S. gordonii or other mouse commensals were present, but had no effect when S. gordonii was inoculated alone. This work thus reveals an additional important inflammasome activation mechanism by which oral keystone pathogens may stimulate periodontal disease progression.
    DOI:  https://doi.org/10.1371/journal.ppat.1014574
  32. Front Amphib Reptile Sci. 2025 ;3 1666714
    The impact of microbiome diversity and composition on host health and susceptibility to disease across amphibian life stages.
    Abigail J Miller, Jamie Voyles.
      Germ-free (i.e., absence of all microbes) and gnotobiotic (i.e., specific known microbial communities) study systems have classically been used to investigate the critical role the microbiome plays in the development of the host immune system. To date, most systems that have been used to experimentally manipulate the microbiome have been developed in model organisms, such as mice and pigs. However, amphibians are rapidly emerging as a valuable model for studying host-microbiome interactions and their effects on health and immunity, especially in the context of infectious disease. Amphibians are a particularly compelling system because, unlike many current systems, they include many species that do not need direct parental care during development, and they undergo a complete reorganization of their immune system during metamorphosis. Amphibians are a group of particular conservation importance as they are currently affected by the infectious disease chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis. Here, we review current research aimed at manipulating the amphibian microbiome through the use of antimicrobial treatments, with a focus on how a depletion of the microbiome diversity influences host development, immunity, and susceptibility to infectious disease. We structure our review in three parts: (1) how microbiome depletion affects chytridiomycosis disease dynamics, (2) how microbiome bioaugmentation through the use of probiotics influences susceptibility to chytridiomycosis, and (3) how microbiome depletion affects amphibian health across different life stages. Overall, research on this topic is important for the conservation of wild amphibian populations because it adds to understanding of the amphibian immune system and susceptibility to disease, both of which are important to inform management strategies and optimize potential therapeutics to aid susceptible populations.
    Keywords:  Batrachochytrium dendrobatidis; amphibian; disease susceptibility; gnotobiotic; health; microbiome
    DOI:  https://doi.org/10.3389/famrs.2025.1666714
  33. Lett Appl Microbiol. 2026 Sep 17. pii: ovag082. [Epub ahead of print]
    Isolation and Characterization of Lytic Bacteriophages Targeting Clinical Staphylococcus Other Than S. aureus.
    Gerardo Antonio Romero-Borja, Luis Enrique Jiménez-Camacho, Victoria Abigail Sánchez-Herrera, Daniel Huelgas-Méndez, Jesús Guillermo Jiménez-Cortes, Luis Esaú López-Jácome, Jossue Ortiz-Álvarez, Rafael Franco-Cendejas, Clara Estela Díaz-Velásquez, Felipe Vaca-Paniagua, Reyna Lara-Martínez, Luis Felipe Jiménez-García, Fahad Mabood Hussein, Altaf Khan, Frederic Cadet, Thomas K Wood, Ana María Fernández-Presas, Rodolfo García-Contreras.
      Staphylococcus spp., other than S. aureus (SOSA, formerly CoNS), are opportunistic pathogens often linked to biofilm infections on indwelling devices. Their rising antibiotic resistance highlights the need for novel therapies. Bacteriophages are promising due to their specificity and ability to inhibit cell growth and biofilm formation. In this study, lytic phages isolated from swab pools were characterized against six clinical S. epidermidis and S. warneri isolates. Two distinct groups were identified via their host range, transmission electron microscopy, and genome sequencing. Group 1 phage ΘBRJ9 belongs to genus Sepunavirus (Myoviridae), while Group 2 phage ΘBRJ18 belongs to genus Andhravirus (Podoviridae). Both showed rapid adsorption, short latent periods (20 min), and high burst sizes (79 and 60 PFU/cell). They strongly inhibited planktonic SOSA growth at MOI 10, with efficacy comparable to or better than vancomycin, and their genomes lacked lysogeny, virulence, or resistance genes. These phages display a lytic lifestyle and are candidates for targeted SOSA therapies. Future work will assess biofilm efficacy, antibiotic synergies, and in vivo performance.
    Keywords:  Antibiotic resistance; Bacterial infection; Clinical strains; Phage genomics; Staphylococci
    DOI:  https://doi.org/10.1093/lambio/ovag082
  34. Periodontol 2000. 2026 Sep 16.
    From mouth to brain: Linking periodontal and peri-implant dysbiosis to systemic inflammation and neuropathology.
    Emilio A Cafferata, Frank Schwarz, Jaime Díaz-Zúñiga, Alpdogan Kantarci.
       BACKGROUND/AIM: Growing evidence suggests that imbalances occurring within the human microbiota and deregulation of the host immune response may play a significant role in the development of neurodegenerative diseases.
    MATERIALS AND METHODS: A comprehensive narrative review of the latest experimental, clinical, and epidemiological insights was conducted to explore the associations among oral dysbiosis, including periodontitis and peri-implantitis, a low-grade inflammatory phenotype, and biological pathways that may contribute to the onset of neuroinflammation and neuropathologies.
    RESULTS: Periodontitis is a chronic inflammatory non-communicable disease driven by subgingival dysbiosis, increasingly linked not only to progressive bone and tooth loss but also to a broad range of systemic chronic non-communicable diseases. Indeed, the persistent burden of deregulated chronic inflammation not only exacerbates periodontal tissue destruction but also promotes a low-grade inflammatory phenotype that may predispose patients to a spectrum of degenerative diseases, such as neurodegenerative disorders. In contrast, evidence regarding peri-implantitis remains comparatively limited and indirect, although emerging data indicate potential systemic inflammatory and cognitive implications.
    CONCLUSION: Elucidating the intricate interactions between oral dysbiosis, periodontal diseases, chronic inflammation, and neurodegeneration is essential for understanding oral health's systemic implications for neurodegenerative and age-related diseases. Current evidence supports an association between oral dysbiosis, chronic oral inflammation, and pathways relevant to neurodegeneration, particularly for periodontitis. However, important knowledge gaps remain, especially concerning peri-implant diseases, where human data are limited.
    CLINICAL RELEVANCE: Effective management strategies targeting periodontal and peri-implant dysbiosis and restoring the immune imbalance may offer novel avenues for promoting healthy aging and preventing neuropathic morbidities.
    Keywords:  blood–brain barrier; chronic low‐grade inflammation; cognitive decline; neuroinflammation; oral dysbiosis; periodontitis; peri‐implantitis; systemic inflammation
    DOI:  https://doi.org/10.1111/prd.70075
  35. J Gen Virol. 2026 09;107(9):
    Amino acid homorepeats in tape measure proteins correlate with bacteriophage tail length.
    Antonio Moreno-Rodríguez, Antonio J Pérez-Pulido, Pablo Mier.
      The tape measure protein (TMP) dictates the tail length of tailed bacteriophages. However, the sequence features that drive the process of length fine-tuning have not yet been described. Tandem repeats (TRs), stretches of aas organized as multiple adjacent copies of the same or very similar sequence motif, are contributors to TMP length variation. Homorepeats (polyX regions) are a specific type of TRs composed of stretches of identical aas, forming low-complexity regions that contribute to protein structural flexibility and dynamics. Here, we performed a large-scale analysis of polyX regions across 12 million phage proteins to test whether these homorepeats help explain the variable length of flexible phage tails. PolyX tracts were detected in 41% of all phage proteins and in 95.5% of TMPs, with polyA, polyG, polyS and polyT dominating the composition. Furthermore, the number of polyX tracts in TMPs scaled directly with protein length. About half of the TMPs have both polyX and TRs (23,469 out of 45,500 TMPs), but nearly half of the polyX-containing TMPs lacked any TRs (19,999 out of 43,468 TMPs), showing that polyX are independent features rather than by-products of larger repeats. Morphological comparisons showed that phages with long and flexible tails (Siphovirus morphotype) combine polyX and TRs, whereas shorter or contractile-tailed phages rely mostly on polyX. Last, the total aa content in polyX regions correlated significantly with experimentally measured tail lengths (R²=0.811, P=1.56×10-⁴). Our results identify polyX tracts as an important and tunable component of TMPs that enable precise control of phage tail length.
    Keywords:  homorepeat; phage; phage tail; tandem repeat; tape measure protein
    DOI:  https://doi.org/10.1099/jgv.0.002341
  36. Foot Ankle Surg. 2026 Sep 16. pii: S1268-7731(26)00253-5. [Epub ahead of print]
    Offloading strategies for diabetic foot ulcers: A systematic review and network meta-analysis of randomized controlled trials.
    Poonsak Koonalinthip, Prut Koonalintip, Nantawan Koonalinthip.
       BACKGROUND: Previous network meta-analyses of diabetic foot ulcer (DFU) offloading focused mainly on non-surgical interventions, leaving the role of surgical offloading uncertain. This study compared and ranked surgical and non-surgical offloading strategies for DFU healing.
    METHODS: Randomized controlled trials (RCTs) evaluating offloading interventions for DFUs were systematically reviewed. The primary outcome was ulcer healing rate. A random-effects network meta-analysis was performed, and interventions were ranked using P-scores.
    RESULTS: Twenty-eight RCTs, involving 2016 participants, were included. Because the primary analysis demonstrated network inconsistency, conclusions were based on a sensitivity analysis that resolved inconsistency. Surgical offloading (RR 1.47), non-removable knee-high customized devices (RR 1.36), and non-removable knee-high prefabricated devices (RR 1.32) were superior to usual care.
    CONCLUSIONS: Surgical offloading and non-removable knee-high devices demonstrated the most robust effectiveness for DFU healing, supporting current guideline recommendations and the use of surgical offloading in selected patients.
    LEVEL OF EVIDENCE: Level I.
    Keywords:  Device; Diabetic Foot Ulcer; Network Meta-Analysis; Offloading; Wound Healing
    DOI:  https://doi.org/10.1016/j.fas.2026.09.010
  37. Front Vet Sci. 2026 ;13 1916814
    Multidrug resistance and biofilm formation among bacterial isolates from chronic wounds in animals: evaluation of anti-biofilm activity.
    Safia Arbab, Hanif Ullah, Suleman, Mazen Almehmadi, Mamdouh Allahyani, Abdulelah Aljuaid, Khalid Jambi, Mustafa H Halawi, Chao Feng.
      Chronic wound infections in animals represent a growing clinical challenge due to the emergence of multidrug-resistant (MDR) bacteria and their ability to form biofilms, which significantly reduce treatment efficacy and promote persistent infection. This study aimed to characterize the bacterial profile, antimicrobial resistance patterns, biofilm-forming capacity, and anti-biofilm activity of agents against bacterial isolates recovered from chronic wound specimens. A total of 96 wound samples were analyzed, of which 84 (87.5%) yielded positive bacterial growth. The predominant bacterial isolates were Staphylococcus aureus (33.3%), followed by Pseudomonas aeruginosa (27.4%), Escherichia coli (19.0%), and Klebsiella spp. (11.9%). Antimicrobial susceptibility testing revealed high resistance to β-lactam antibiotics, with ampicillin showing the highest resistance rate (78.6%), whereas imipenem exhibited the lowest resistance (14.3%). Overall, 63.5% of isolates were classified as multidrug-resistant. Biofilm analysis demonstrated that 38.1% of isolates were strong biofilm producers, with strong biofilm-forming strains exhibiting higher minimum inhibitory concentration (MIC) values compared with weak and non-biofilm producers. Evaluation of anti-biofilm agents showed that silver nanoparticles, chitosan nanoparticles, and DNase enzyme reduced biofilm biomass by 72%, 65%, and 58%, respectively. These findings highlight the critical role of biofilm-mediated resistance in chronic wound infections and emphasize the need for integrated antimicrobial and anti-biofilm strategies for effective management of MDR bacterial infections.
    Keywords:  MIC; antimicrobial susceptibility; biofilm; chronic wound infections; multidrug resistance; veterinary microbiology
    DOI:  https://doi.org/10.3389/fvets.2026.1916814
  38. Front Cell Dev Biol. 2026 ;14 1915007
    Gut microbiota dysbiosis and the gut-lung axis in COPD: mechanisms, clinical relevance, and microbiota-targeted interventions.
    Yinghui Chai, Junya Lan, Kang Li, Xue Mei, Yanan Chen, Nannan Zhou, Xin Liu, Wenping Gong, Hong Lei.
      Chronic obstructive pulmonary disease (COPD), which is characterised by persistent inflammation and airflow limitation, has increasingly been linked to the gut-lung axis. Patients with COPD commonly exhibit reduced diversity of gut microbiota, decreased levels of bacteria that produce short-chain fatty acids (SCFAs), increased levels of opportunistic pathogens, and compromised intestinal barrier function. These alterations are driven by factors such as smoking, hypoxia, oxidative stress, medication use and ageing, and promote bacterial translocation and systemic inflammation, thereby exacerbating lung injury. Gut microbiota metabolites, including SCFAs, bile acids, tryptophan metabolites and trimetlylamine N-oxide (TMAO), further modulate immune responses and metabolic pathways, thereby influencing disease progression. Intervention strategies targeting the microbiome, including dietary fibre, probiotics, prebiotics, faecal microbiota transplantation (FMT) and phage therapy, have demonstrated potential therapeutic value, though clinical evidence remains limited. Elucidating the mechanisms linking gut dysbiosis and COPD will provide novel targets for precision interventions and disease management.
    Keywords:  chronic obstructive pulmonary disease; dysbiosis; gut microbiota; gut–lung axis; microbial metabolites; systemic inflammation
    DOI:  https://doi.org/10.3389/fcell.2026.1915007
  39. Cell Biochem Funct. 2026 Sep;44(9): e70309
    Mechanistic Pathways of Wound Healing: From Hemostasis to Scar-Free Regeneration.
    Devadass Jessy Mercy, Koyeli Girigoswami, Agnishwar Girigoswami.
      Wound healing is the critical process regulated through a harmonious coordination of cellular, molecular, pathological, and systemic communications. Normally, healing occurs in four overlapping phases, which are modified and controlled by various growth factor interactions and signaling pathways. Disruption of the tightly coordinated wound-healing cascade, together with aberrant protein signaling, mitochondrial dysfunction, antimicrobial resistance, sustained fibroblast activation, and maladaptive epigenetic reprogramming, drives pathological tissue repair culminating in chronic non-healing wounds, including diabetic, ischemic, and venous ulcers, as well as fibrotic outcomes such as hypertrophic and keloid scarring. The persistent fibroblast activation, reduced apoptosis, prolonged TGF-β activity, and severe fibrosis induced by mechanical methods trigger excessive healing, while existing therapies fail to manage these functions. Therefore, in order to develop advancements toward precise and personalized medicine, it is important to understand the various mechanisms involved in wound healing. The current review provides a comprehensive understanding of various fundamental mechanisms involved in wound healing, such as cellular, molecular, signaling pathways, genetic, epigenetic, pathological, immunological, and systemic mechanisms. Knowledge of these mechanisms and how they work under physiological as well as pathological conditions connects to clinical inefficiency, which helps to provide accurate medicine. A deeper mechanistic knowledge paves the way for developing innovative biomaterials; nanotechnology-based therapeutic strategies, specific drug delivery, molecular biomarkers, and scar-free healing of wounds, which enrich the future with advanced therapeutics and personalized medicine for wounds.
    Keywords:  cellular mechanism; chronic wounds; extracellular matrix; health care; therapy
    DOI:  https://doi.org/10.1002/cbf.70309
  40. Front Cell Infect Microbiol. 2026 ;16 1859658
    The gut microbiota in Graves' disease: mechanistic insights and clinical implications.
    Leyang Li, Boxian Pang, Ze Wang, Di Zhao, Junping Wei, Qiuhong Wang.
      Graves' disease (GD) is an autoimmune form of hyperthyroidism characterized by loss of immune tolerance to the thyrotropin receptor and sustained thyroid hormone excess. Interest in the gut-thyroid axis has expanded rapidly, placing the gut microbiota within current models of GD pathophysiology. This review summarizes current evidence on gut microbial alterations in GD and discusses how these changes may intersect with thyroid autoimmunity. Available studies broadly support disruption of the intestinal microbial ecosystem in GD, although findings for individual taxa and diversity indices vary across cohorts. Proposed links between dysbiosis and disease include altered short-chain fatty acid and bile acid metabolism, impairment of epithelial barrier integrity with translocation of microbial products, shifts in Th17/Treg balance and related immune activation, molecular mimicry, and disturbed handling of micronutrients involved in thyroid hormone synthesis and metabolism. The oral-gut microbial connection has also emerged as a potentially relevant dimension of disease-associated dysbiosis. In parallel, microbiota-directed approaches, including probiotics, prebiotics, synbiotics, dietary modulation, and fecal microbiota transplantation, are being explored as possible adjuncts in GD management. Overall, gut microbial disturbance offers a biologically plausible link between environmental exposure, immune disequilibrium, and thyroid dysfunction in GD; however, stronger mechanistic, longitudinal, and interventional evidence is still required before these findings can be translated into precision clinical practice.
    Keywords:  Graves’ disease; gut microbial metabolites; gut microbiota; gut–thyroid axis; thyroid autoimmunity
    DOI:  https://doi.org/10.3389/fcimb.2026.1859658
  41. Adv Genet (Hoboken). 2026 Sep;7(3): e70046
    Foundation Models for Microbiome Research: From Sequence Semantics to Community Dynamics and Multimodal World Models.
    Haohong Zhang, Zixin Kang, Kang Ning.
      Microbiome sequencing has advanced faster than microbiome understanding. Although large-scale 16S, metagenomic, metatranscriptomic, and proteomic datasets have accumulated rapidly, most analyses remain cohort-specific and association-driven, limiting mechanistic insight, cross-study transferability, and robustness to technical confounding. Foundation models offer a new computational framework by learning reusable biological representations from large unlabeled datasets. In this Review, we present microbiome foundation models as a hierarchy spanning biological scales. Sequence-centric models capture the syntax and semantics of DNA and proteins for taxonomic inference, functional annotation, and generative design. Community-centric models learn ecological structure from abundance profiles, while addressing compositionality, sparsity, and the unordered nature of microbial communities. Emerging multimodal frameworks integrate sequence-derived functional potential with community-level ecological dynamics under host and environmental context. We discuss key design choices, including tokenization, representation granularity, self-supervised objectives, and evaluation strategies, and highlight challenges in interpretability, domain shift, causal reasoning, and biological validation. Finally, we propose a transition from static representation learning toward intervention-aware microbiome world models capable of simulation, digital twinning, and generative microbiome engineering.
    Keywords:  artificial intelligence; bioinformatics; microbiome
    DOI:  https://doi.org/10.1002/ggn2.70046
  42. J Int Soc Prev Community Dent. 2024 Jul-Aug;16(4):16(4): 423-434
    The 100 Most-Cited Articles on Periodontal Disease and Atherosclerosis: A Bibliometric Study (1989-2025).
    Liang Chen, Wenhui Kong, Xiao Luan, Shengnan Zhang, Hui Li, Yi Du, Jing Sun.
       Objective: The association between periodontal disease and atherosclerosis has gained significant attention, yet the intellectual structure and most influential works in this interdisciplinary field have not been systematically mapped. This study aimed to identify and analyze the characteristics, collaborative networks, and evolving research trends of the 100 most-cited articles concerning the relationship between periodontal disease and atherosclerosis.
    Methods: A comprehensive search was performed in the Web of Science Core Collection on January 24, 2025. Bibliometric analysis and visualization were conducted using VOSviewer, CiteSpace, and the "bibliometrix" R package. Metrics included total citations, h-index, and keyword burst detection.
    Results: The 100 articles garnered a total of 13,968 citations (average: 195.6 citations per article). The United States was the leading contributor (n = 40), with the University of North Carolina identified as the most productive institution. The Journal of Periodontology and Circulation were the primary publication venues. Keyword clustering identified six research hotspots: risk factors, inflammatory responses, infection, confounding variables, Porphyromonas gingivalis, and related cardiovascular conditions. Burst analysis revealed a paradigm shift in research focus from mechanistic "infection" (2004-2005) to clinical "therapy" (2013-2020).
    Conclusion: This study delineates the foundational literature and thematic evolution of the periodontal-atherosclerosis link. The observed shift in the literature from mechanistic to interventional studies may correlate with an increase in publications on periodontal treatment for cardiovascular prevention. These findings provide a data-driven roadmap for future longitudinal trials and clinical guidelines.
    Keywords:  Atherosclerosis; CiteSpace; VOSviewer; bibliometric analysis; cardiovascular health; periodontal disease
    DOI:  https://doi.org/10.4103/jispcd.jispcd_214_25
  43. Front Artif Intell. 2026 ;9 1795751
    A severity-aware multi-task CNN-transformer framework for explainable diabetic foot ulcer triage and mobile deployment.
    Abdullah, Muhammad Ateeb Ather, Zulaikha Fatima, José Luis Oropeza Rodríguez.
       Introduction: Diabetic foot ulcer (DFU) image classification can support timely clinical triage; however, many existing systems provide limited severity granularity, rely on single-source image datasets, and predominantly use pixel-level explanation methods. This study developed a seven-class, severity-aware, multi-task artificial intelligence framework for interpretable DFU image analysis and smartphone-class deployment.
    Methods: The framework combines domain-adaptive SimCLR pretraining, U-Net-based image refinement, EfficientNet-B0 feature extraction, a lightweight windowed transformer fusion block, and parallel classification and ordinal severity-regression heads. Four public data sources-DFUC 2020/2021, AZH, Medetec, and an IWGDF-aligned ordinal repository-were harmonized and deduplicated, yielding an analytical corpus of 24,925 original images. Evaluation included a 3,739-image held-out test set, five-fold stratified cross-validation, leave-one-source-out testing, an independent prospective clinician-audited cohort of 366 images, calibration and uncertainty analyses, concept-based interpretability assessment, and mobile-device profiling.
    Results: On the held-out test set, the framework achieved 95.5% accuracy (95% CI, 94.7-96.1) and a macro F1 score of 0.953, while mean five-fold cross-validation accuracy was 96.5% ± 0.3 percentage points. External ordinal severity estimation yielded a Spearman correlation of ρ = 0.91. In the clinician-audited cohort, weighted Cohen's κ for model-clinician severity agreement was 0.952. Model-assisted review was associated with a change in recorded management intent in 27.6% of cases, and 92.6% of generated explanations were rated as clinically useful. Full on-device inference, including gradient-weighted class activation mapping and concept-based explanation generation, required 322 ms per image on a Snapdragon 8 Gen 1 device.
    Discussion: The proposed framework demonstrates how multi-source representation learning, multi-task severity modeling, uncertainty assessment, concept-based interpretability, and efficient edge deployment can be integrated within a unified AI pipeline for DFU image analysis. The findings indicate high classification performance, strong ordinal severity agreement, clinically interpretable outputs, and technically feasible smartphone-class inference. Further multicenter prospective validation across diverse populations and acquisition conditions is required before translation into routine clinical decision-support settings.
    Keywords:  diabetic foot ulcer; explainable artificial intelligence; external validation; hybrid CNN–transformer; mobile deployment; multi-task learning; self-supervised learning; severity classification
    DOI:  https://doi.org/10.3389/frai.2026.1795751
  44. Front Med (Lausanne). 2026 ;13 1929792
    The application of artificial intelligence in systemic lupus erythematosus: a bibliometric analysis of current trends and future directions.
    Ziyi Liu, Wenqian Yu, Xinxin Meng, Jiaying Yan, Qiang Fu.
       Background: Systemic lupus erythematosus (SLE) poses significant clinical challenges due to its heterogeneity and unpredictable relapses. Artificial intelligence (AI) is driving a paradigm shift in SLE management through molecular subtyping and prognostic modeling. However, a comprehensive quantitative analysis of this rapidly growing field is lacking. This study employs bibliometric and visualization methods to systematically map the development, collaboration patterns, and research frontiers of AI in SLE.
    Methods: English-language original articles and reviews on AI in SLE, published between January 1, 2005, and June 10, 2026, were retrieved from the Web of Science Core Collection and Scopus. After rigorous screening, 707 core publications were analyzed using R-Bibliometrix, VOSviewer, and CiteSpace to evaluate publication trends, collaboration networks, keyword co-occurrence, and citation bursts.
    Results: The 707 included publications demonstrated a polynomial accelerated growth trend since 2005. Research has evolved from algorithmic proof-of-concepts to deep learning and multi-omics integration. China and the United States lead global output and collaboration, with institutions like the Karolinska Institute showing significant impact. Although "machine learning" and "lupus nephritis" remain core topics, the research focus has expanded. Current studies increasingly emphasize molecular stratification, automated pathological image classification, and the longitudinal prediction of flares and organ damage. Recent citation bursts for "immunosuppressive agent," "tacrolimus," and "prednisone" highlight personalized treatment efficacy prediction as the latest frontier.
    Conclusion: AI has matured from methodological exploration into a robust clinical decision-support tool for SLE, particularly for lupus nephritis assessment and flare prediction. Future advancements rely on conducting prospective clinical validations in real-world cohorts, predicting personalized drug efficacies, and leveraging multi-omics to decode pathological mechanisms. These steps are essential to transition SLE management from traditional empirical approaches to data-driven precision medicine.
    Keywords:  artificial intelligence; bibliometrics; precision medicine; systemic lupus erythematosus; visual analytics
    DOI:  https://doi.org/10.3389/fmed.2026.1929792
  45. J Oral Microbiol. 2026 ;18(1): 2728748
    Harmonized multi-cohort analysis of oral microbiome development during early lifetime.
    Do Yeon Won, Si Yeong Kim, Seon Mi Kim, Hyewon Shin, Hee Sam Na, Jin Chung.
       Background: Early-life assembly of the oral microbiome may influence oral and systemic health, yet developmental patterns are difficult to compare across studies because of differences in sampling and analytical workflows. We conducted a harmonized cross-cohort re-analysis of longitudinal pediatric 16S rRNA datasets spanning birth to early childhood.
    Methods: Five publicly available longitudinal cohorts from birth to seven years were curated and independently reprocessed using QIIME 2 and R. Taxonomy was assigned using the Human Oral Microbiome Database (HOMD). Alpha and beta diversity, taxonomic composition, and species-level temporal dynamics were evaluated. Age was harmonized to months and summarized into three developmental intervals: birth-12 months, 12-36 months, and >36 months. Temporal clustering used fuzzy c-means clustering (TCseq).
    Results: Alpha diversity increased rapidly during the first year, plateaued between one and three years, and increased gradually thereafter. Beta diversity showed the greatest compositional shifts during infancy, followed by relative stabilization. Taxonomic profiling revealed reproducible succession from Streptococcus and Staphylococcus to Haemophilus, Neisseria, and Veillonella, followed by Prevotella and Campylobacter after three years. Temporal clustering identified three developmental groups corresponding to early, transitional, and later-expanding taxa.
    Conclusions: This harmonized analysis of five longitudinal cohorts demonstrates a reproducible three-phase trajectory of oral microbiome maturation during early childhood. The most pronounced microbial restructuring occurred during infancy, followed by community stabilization and gradual maturation. These findings provide a framework for understanding age-associated microbial succession and identifying developmental windows for preventive interventions in pediatric oral health.
    Keywords:  16S rRNA; Oral microbiome; alpha/beta diversity; early childhood; longitudinal; multi-cohort analysis; pediatric dentistry; succession; temporal clustering
    DOI:  https://doi.org/10.1080/20002297.2026.2728748
  46. Microbiol Spectr. 2026 Sep 16. e0422525
    In-host adaptation of Staphylococcus aureus during recurrent prosthetic joint infections: a retrospective longitudinal study.
    Charles Maurille, François Gravey, Jean-Christophe Giard, Jocelyn Michon, Goulven Rochcongar, Bertrand Lecoeur, Renaud Verdon, Simon Le Hello, Christophe Isnard.
      The aim of this study was to characterize the in vivo evolution of Staphylococcus aureus strains involved in recurrent prosthetic joint infections (PJIs) both phenotypically and genomically. We conducted a monocentric retrospective study in a 1,437-bed French teaching hospital between 2013 and 2021. All patients presenting a recurrent S. aureus-related PJI-defined as at least two strains isolated from distinct clinical samples more than 90 days apart-of the knee, hip, or shoulder were included. Clinical data were reviewed, and all isolates underwent phenotypic characterization, including antimicrobial susceptibility testing, growth rate determination, biofilm production assays, metabolic profiling (API 50 CH), and virulence evaluation using the Galleria mellonella infection model. Whole-genome sequencing (WGS) was performed for all strains, followed by analyses of core-genome multilocus sequence typing (cgMLST), resistome, virulome, and mobilome composition, and single-nucleotide polymorphisms (SNPs). Thirteen patients met inclusion criteria, yielding 55 S. aureus isolates. Eight patients experienced recurrent infections caused by genetically closely related strains throughout the clinical course (median: three strains per patient; range: 2-6), whereas five patients were infected by genetically distinct strains. At baseline, isolates were genetically diverse and susceptible to methicillin and rifampicin; two showed fluoroquinolone resistance due to grlA and/or gyrA mutations. In one patient (patient C), a recurrent isolate acquired an rpoB S486L mutation, conferring rifampicin resistance after rifampicin exposure. Due to the limited sample size, it is difficult to draw definitive conclusions from the phenotypic analyses. This study highlights the adaptive evolution of S. aureus during chronic PJIs and underscores the need for further research to better understand intra-host dynamics in long-standing infections.
    IMPORTANCE: This study conducted in a 1,437-bed French teaching hospital analyzed the genomic and phenotypic evolution of 55 Staphylococcus aureus strains recovered in recurrent PJIs from 13 patients. The first strains showed high genotypic diversity across 12 different sequence types. Among the 13 patients, only eight experienced a true recurrence with the same strain, while five were contaminated with a different strain of S. aureus, indicating a new infection. Moreover, this study underscores the complex within-host evolution of S. aureus and highlights the phenotypical and genotypical adaptation during chronic infection.
    Keywords:  Staphylococcus aureus; genomic; prosthetic joint infections; recurrence; virulence
    DOI:  https://doi.org/10.1128/spectrum.04225-25
  47. Front Cell Infect Microbiol. 2026 ;16 1896617
    From oral infection to pulmonary inflammation: periodontal pathogens and their potential role in COPD susceptibility.
    Xiaohao Liu, Yan Chai, Fengxiang Shi, Bingchun Li, Jiawei Zeng, Jiaming Bi, Shuaimei Xu, Buling Wu.
       Background: Oral health significantly impacts overall health. Periodontal disease and chronic obstructive pulmonary disease (COPD) are prevalent chronic inflammatory conditions among older adults, but their causal link is not well-established.
    Methods: Multivariable logistic regression, including subgroup, sex-stratified, and interaction analyses, was used to investigate the link between self-reported periodontal disease and COPD. Two-sample Mendelian randomization (MR) was utilized to explore causality, primarily through inverse-variance weighting (IVW), and supported by four additional MR approaches. Sensitivity analyses were performed to evaluate pleiotropy and heterogeneity. Normal human bronchial epithelial cells were stimulated in vitro with the periodontal pathogens F. nucleatum and P. gingivalis. The expression levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were then quantified using qPCR and chemiluminescence immunoassay. In vivo, a combined rat model of periodontitis and COPD was established to compare pulmonary inflammatory severity with a COPD-only model.
    Results: Multivariable logistic regression revealed significant associations between self-reported periodontal disease, oral hygiene practices, and COPD. The self-reported periodontal disease-COPD association was moderated by hypertension and flossing behavior. Mendelian randomization studies provided suggestive, exploratory evidence that periodontal disease may be associated with a higher risk of COPD in European populations, although the association did not survive multiple-testing correction and was not observed in East Asian populations. In vitro, both pathogens significantly upregulated IL-6 and IL-8 at both mRNA and protein levels. In vivo, rats with comorbid periodontitis and COPD exhibited significantly exacerbated pulmonary inflammation compared with those having COPD alone.
    Conclusion: Periodontal disease may promote COPD pathogenesis, with in vitro data supporting a direct pro-inflammatory role of P. gingivalis and F. nucleatum in airway epithelium. In vivo, periodontitis as a complex disease state exacerbates pulmonary inflammation in COPD. Maintaining good oral hygiene may represent a potential supportive strategy that warrants further investigation in interventional studies, with potential public health implications, especially among high-risk populations.
    Keywords:  chronic obstructive pulmonary disease; inflammation; oral health; periodontal disease; periodontal pathogens
    DOI:  https://doi.org/10.3389/fcimb.2026.1896617
  48. Mayo Clin Proc Digit Health. 2026 Dec;4(4): 100392
    Prediction Models for Periprosthetic Joint Infection: A Systematic Review of Traditional and Machine Learning Approaches.
    Farzad Pourghazi, Seyed Mohammad Amin Alavi, Fabio Borgonovo, Francesco Petri, Takahiro Matsuo, Matthew P Abdel, Cody C Wyles, Andrea Gori, Aaron J Tande, Elie F Berbari.
       Objective: To systematically review the development, validation, and performance of traditional and machine learning (ML) prediction models for periprosthetic joint infection (PJI) risk, diagnosis, and clinical outcomes.
    Methods: We conducted a systematic review according to PRISMA guidelines to identify studies that developed or validated multivariable prediction models for PJI using traditional statistical or ML approaches. Searches were performed on December 10, 2025, across Ovid Embase, MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and CENTRAL.
    Results: Among 4565 identified records, 34 studies met inclusion criteria. Reported discrimination varied across model types and clinical end points. Among traditional risk-prediction models, 54.5% showed acceptable or good discrimination (0.7 ≤ area under the receiver-operating characteristic curve [AUROC] < 0.8), and 27.3% showed excellent discrimination (0.8 ≤ AUROC < 0.9). Traditional diagnostic and outcome prediction models showed good to outstanding discrimination. Among ML models, 50.0% of risk models showed acceptable or good discrimination (0.7 ≤ AUROC < 0.8), while 60.0% of diagnostic models reported AUROC of 0.9 or more. However, calibration reporting was inconsistent, particularly among ML studies, and external validation was limited. Model performance generally decreased in external validation cohorts compared with derivation cohorts. Substantial heterogeneity among included studies and model designs precluded direct crossmodel comparisons; therefore, differences in AUROC should not be interpreted as evidence of superiority between approaches.
    Conclusion: Prediction models for PJI demonstrate variable performance across risk prediction, diagnosis, and outcome prediction settings. However, substantial clinical and methodological heterogeneity, limited calibration reporting, and inadequate external validation restrict assessment of model reliability and generalizability. Current evidence does not support conclusions regarding the superiority between approaches.
    DOI:  https://doi.org/10.1016/j.mcpdig.2026.100392
  49. Environ Microbiol Rep. 2026 Oct;18(5): e70415
    A Bacillus Phage From Bangladeshi Soil, Phage APU1: Genomic Characterisation and Comparative Genomic Analysis.
    Arefeen Haider, Tasnuva Jahan Esha, Sezanur Rahman, Jannat Akther, Naimul Islam Faysal, Tahsin Khan, Shakhinur Islam Mondal, Anowara Begum, Sudhangshu Kumar Biswas, Mustafizur Rahman, Mohammad Jubair.
      Bacillus species are environmentally resilient bacteria associated with soil, food, industrial settings and opportunistic infections, yet their bacteriophages remain incompletely characterised, particularly from underexplored environmental sources. We isolated and characterised phage APU1, a dsDNA phage from agricultural soil in Bangladesh. Partial 16S rRNA gene sequencing identified the enrichment host conservatively as Bacillus sp. APU1 has a 153,847 bp genome that encodes 236 predicted proteins, including 84 shorter than 100 amino acids. CheckV classified the genome as high-quality, with an estimated completeness of 99.91% and no detectable host-gene contamination. Functional annotation identified genes associated with DNA replication, structural assembly, packaging and host lysis. PhaBOX classified APU1 as virulent, with PhaTYP and CHERRY prediction scores of 1.0. CARD/VFDB screening did not detect CARD-listed antimicrobial resistance genes or VFDB-listed virulence factor genes. Comparative genomic analyses using VICTOR, VIRIDIC and VIPTree placed APU1 within a group of related Bacillus phages. APU1 shared 89.7%-89.8% intergenomic similarity with its closest relatives, supporting its classification as a genomically distinct phage within this group. This study expands the genomic catalogue of Bacillus-associated phages from Bangladeshi soil and provides a foundation for future studies on phage diversity, host range, morphology and biological properties.
    Keywords:  bacillus bacteriophage; comparative genomics; soil virome
    DOI:  https://doi.org/10.1111/1758-2229.70415
  50. Respir Investig. 2026 Sep 15. pii: S2212-5345(26)00149-8. [Epub ahead of print]64(6): 101515
    Lung microbiome alterations in idiopathic pulmonary fibrosis and hypersensitivity pneumonitis: A systematic review with insights into microbiome-host interactions and the gut-lung axis.
    Sanjukta Dasgupta, Sushmita Roychowdhury, Koel Chaudhury.
      The lung microbiome is increasingly recognized as an important factor in idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP), two interstitial lung diseases with overlapping clinical features but distinct underlying mechanisms and management. This systematic review, conducted in accordance with PRISMA guidelines, evaluated the current evidence regarding lung microbiome alterations in IPF and HP. A literature search was performed using PubMed as the primary database and supplemented by Google Scholar searches. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261415180). Fourteen unique studies met the inclusion criteria, comprising 13 studies involving IPF and 2 studies involving HP, with one study overlapping between the two disease groups. Current evidence suggests that IPF is associated with increased bacterial burden, reduced microbial diversity, and enrichment of specific taxa, including Streptococcus and Staphylococcus, which have been linked to immune activation and fibrotic progression. In contrast, limited available evidence suggests that HP may exhibit a lower bacterial burden, with microbial patterns influenced predominantly by environmental exposures, including bacterial and fungal antigens from occupational and domestic sources. Emerging studies highlight host-microbiome and environment-microbiome interactions in disease progression. Overall, the current evidence supports a role for microbial dysbiosis in IPF, whereas microbiome alterations in HP appear to be more closely associated with environmental microbial exposures. However, conclusions regarding HP should be interpreted cautiously due to the limited number of studies. Further longitudinal and multi-omics studies are needed to clarify causality and identify robust microbial biomarkers for diagnosis and therapy.
    Keywords:  Hypersensitivity pneumonitis; Idiopathic pulmonary fibrosis; Interstitial lung disease; Lung microbiome; Microbial diversity
    DOI:  https://doi.org/10.1016/j.resinv.2026.101515
  51. Curr Oncol Rep. 2026 Sep 15. pii: 93. [Epub ahead of print]28(1):
    The Oral Microbiome in Oral Cavity Cancer: Mechanisms of Carcinogenesis, Biomarkers, and Therapeutic Implications.
    Katarzyna Pazdro-Zastawny, Marcin Kos, Anna Leszczyszyn, Tomasz Zawadzki, Kacper Pietruszka, Karolina Dorobisz.
       PURPOSE OF REVIEW: Oral cavity cancer (OCC) is a significant clinical challenge within head and neck oncology. It is characterized by significant morbidity, high recurrence rates, and only modest improvements in long-term survival over recent decades. Recent advances in metagenomics and high-throughput sequencing have revealed that oral microbial dysbiosis contributes to tumorigenesis, highlighting the potential of microbiome-derived biomarkers for early detection and prognosis of OCC. The purpose of the work is to discuss oral microbiome alterations in OCC.
    RECENT FINDINGS: The microbiome plays a crucial role in regulating the host's physiological, immunological, and metabolic functions. Changes in the composition of the microbiome can influence our health status of local diseases of the oral cavity and oropharynx, as well as systemic diseases. In recent years, the role of the oral microbiome in oral potentially malignant disorders progression and OCC development has been emphasized. Changes in the oral and gut microbiome can lead to the induction of chronic inflammation, modulation of the immune system, and the production of carcinogenic metabolites. Dysbiosis can lead to critical inflammatory responses and consequently contribute to neoplastic events. Microbiome-modulating therapies tailored to the patient's individual profile and aimed at improving cancer treatment outcomes are being introduced, including the introduction of antibiotics to reduce harmful bacteria. Identification of new biomarkers in oral microbiota communities and development of therapeutic strategies in relation with oral microbiota in the future may be one of the pillars of the oral cancer diagnosis and treatment strategy. Oral cancer prevention protocols should include the improvement of oral hygiene as an element of the prevention and treatment of periodontitis. An introduction of microbiota-targeted interventions, including probiotics, prebiotics, and dietary strategies, may reduce the toxicity of radiotherapy, leading to improved patient outcomes.
    Keywords:  Biomarkers; Dysbiosis; Oral cavity cancer; Oral microbiome; Oral squamous cell carcinoma; Periodontitis
    DOI:  https://doi.org/10.1007/s11912-026-01818-y
  52. Curr Opin Infect Dis. 2026 Aug 27.
    Machine learning to differentiate colonization from infection in multidrug-resistant Gram-negative bacteria: implications for further research.
    Daniele Roberto Giacobbe, Elena Ceccardi, Lucia Scarfone, Marco Muccio, Maurizio Fedriga, Antonio Vena, Matteo Bassetti.
       PURPOSE OF REVIEW: Machine learning has emerged as a promising tool to support antimicrobial decision-making in infectious diseases. In colonized patients, distinguishing multidrug-resistant Gram-negative bacteria (MDR-GNB) colonization from true infection remains a major clinical challenge, as both delayed appropriate therapy in severe infections and unnecessary broad-spectrum antimicrobial use may adversely affect patient outcomes and antimicrobial stewardship. This review discusses the current evidence on machine learning models for predicting or detecting MDR-GNB infection in colonized patients, highlights key methodological limitations of the available literature, and outlines future research priorities.
    RECENT FINDINGS: Current evidence specifically evaluating machine learning models beyond logistic regression in MDR-GNB-colonized patients remains limited. Overall, while machine learning may achieve encouraging discriminatory performance, important methodological limitations persist. Most notably, predictive models are frequently developed in heterogeneous populations that do not reflect the clinically relevant populations of colonized patients in which treatment decisions are made. Furthermore, improvements in predictive performance remain modest, possibly reflecting limited sample sizes and data granularity rather than insufficient algorithmic complexity. In our opinion, future advances could require multicenter datasets enriched with longitudinal clinical, microbiological, and genomic information, together with automated feature extraction from electronic health records.
    SUMMARY: The main challenge for machine learning in predicting MDR-GNB infection in colonized patients may lie not in developing increasingly sophisticated algorithms, but in generating clinically representative datasets and adopting rigorous methodological standards for model development, validation, calibration, and implementation. Future research should prioritize clinically meaningful target populations and demonstrate improvements in patient outcomes and antimicrobial stewardship beyond conventional measures of predictive performance.
    Keywords:  antimicrobial resistance; antimicrobial stewardship; artificial intelligence; colonization; machine learning; prediction
    DOI:  https://doi.org/10.1097/QCO.0000000000001240
  53. Nat Microbiol. 2026 Sep 16.
    Prophage-encoding engineered bacteria enable prophylactic lytic phage therapy for enteric infection in mice.
    Rogerio A Bataglioli, Hiba Baaziz, Hallie F Avalos, Lindsay Smith, Zachary R Baker, Rita J Makhlouf, David da Silva Barreira, Harsimran Kaur, Teresa Southard, Bryan B Hsu.
      Phage therapy is a promising antibacterial approach but it has limited efficacy against enteric bacterial infections, such as Salmonella enterica Typhimurium (STm). Here we hypothesized that establishing high concentrations of a pathogen-targeting phage in the gut before infection would prophylactically protect against future infection. To this end, we engineered non-pathogenic Escherichia coli to encode a prophage that produces obligately lytic phage progeny targeting STm while overcoming its host defence systems, including restriction-modification systems. We show that prophylactic gut colonization with this lytic phage-producing lysogen of E. coli produces high levels of lytic phage before infection, inhibits the establishment of STm after infection and improves survival in mouse models of STm-induced colitis. Using a mutant STm strain limited to intestinal colonization, we show that phage-producing E. coli consistently colonized, produced high phage levels and eliminated STm from the intestinal tract. Our findings present a proof-of-concept that prophylactic prophage therapy can protect against an enteric infection.
    DOI:  https://doi.org/10.1038/s41564-026-02484-3
  54. Int J Periodontics Restorative Dent. 2026 Sep 16. 46(5): 537-541
    Refining the Taxonomy of Wound Healing Patterns in Periodontal Therapy.
    Giovanpaolo Pini Prato, Leandro Chambrone, Gustavo Avila-Ortiz.
      
    DOI:  https://doi.org/10.11607/PRD.2026.5.C
  55. Healthcare (Basel). 2026 Aug 23. pii: 2678. [Epub ahead of print]14(17):
    Association Between Periodontitis Severity and Oral Health-Related Quality of Life: A Cross-Sectional Study Using the 2017 Periodontitis Classification.
    Gabriela Zambrano Manzaba, Jazmin Rodríguez Grajales, Hector Alfredo Lema Gutierrez, Luis Chauca Bajaña, Mónica Gabriela Magaña Pérez, Gema Nallely Mendoza Manzaba, Rito Alfonso Salazar Roman, Daniela Galicia-Diez Barroso, Luis David Abeijon Malvaez.
       BACKGROUND: Periodontitis is a chronic inflammatory disease characterized by progressive destruction of the tooth-supporting tissues and may substantially impair oral health-related quality of life (OHRQoL). Although the clinical consequences of periodontitis are well documented, the extent to which disease severity is associated with patient-reported outcomes remains insufficiently understood. This study aimed to evaluate the association between periodontitis severity and OHRQoL and to examine sociodemographic, behavioral, and systemic factors associated with poorer OHRQoL.
    METHODS: A cross-sectional analytical study was conducted among 136 adult patients diagnosed with stage II or stage IV periodontitis at the Periodontology Clinic of Universidad Tecnológica de México (UNITEC). OHRQoL was assessed using the Oral Health Impact Profile for Periodontal Disease (OHIP-14-PD). Sociodemographic characteristics, smoking status, and diabetes mellitus were recorded using a structured questionnaire. Periodontal status was determined through standardized clinical and radiographic examinations. The internal consistency of the OHIP-14-PD was evaluated using Cronbach's alpha coefficient. Bivariate analyses were performed using non-parametric tests. An exploratory, partially adjusted multivariable linear regression model including sex, marital status, diabetes mellitus, and periodontitis stage was also performed.
    RESULTS: Stage IV periodontitis was more prevalent than stage II periodontitis (55% vs. 45%). The mean OHIP-14-PD score was 24.9 ± 13.7, and the instrument demonstrated excellent internal consistency (Cronbach's α = 0.89). Patients with stage IV periodontitis had significantly higher OHIP-14-PD scores than those with stage II disease (30.1 ± 12.4 vs. 18.6 ± 12.6; p < 0.001), indicating poorer OHRQoL. In the bivariate analyses, poorer OHRQoL was also observed among current smokers, participants with diabetes mellitus, those with lower educational attainment, and those with lower socioeconomic status (p < 0.05). In the exploratory partially adjusted model, male sex (β = 4.2; 95% CI: 0.1-8.2; p = 0.042), diabetes mellitus (β = 6.5; 95% CI: 2.1-10.9; p = 0.004), and stage IV periodontitis (β = 4.6; 95% CI: 0.4-8.7; p = 0.031) were associated with higher OHIP-14-PD scores.
    CONCLUSIONS: In this single-center cross-sectional sample, patients with stage IV periodontitis reported higher OHIP-14-PD scores than those with stage II periodontitis. These findings indicate an association within the studied clinical population and should not be interpreted as evidence of a causal effect or as directly generalizable to broader populations. Larger multicenter longitudinal studies including patients across all periodontitis stages are required to confirm the magnitude and external validity of this association.
    Keywords:  OHIP-14; disease severity; oral health-related quality of life; periodontitis
    DOI:  https://doi.org/10.3390/healthcare14172678
  56. Tissue Eng Part B Rev. 2026 Sep 17. 19373368261486381
    Pathological Microenvironment-Guided Smart Hydrogels for Periodontitis Therapy.
    Wei He, Tianming Lu, Xiaohong Chen, Ping Liu.
      Periodontitis is a chronic inflammatory disease initiated by dental plaque biofilms and mediated by dysregulated host immune responses, frequently resulting in irreversible alveolar bone resorption. Although mechanical debridement, local drug delivery, and antimicrobial therapies are widely applied in clinical practice, their therapeutic efficacy remains limited by insufficient drug retention, nonspecific drug release, antibiotic resistance, and inadequate periodontal tissue regeneration. Recently, smart hydrogels have emerged as promising platforms for periodontal therapy owing to their ECM-mimicking three-dimensional networks, excellent biocompatibility, and ability to respond to specific stimulus signals. Therefore, this review focuses on design strategies for smart hydrogels driven by the periodontal pathological microenvironment, guiding the development of hydrogels responsive to both endogenous and exogenous stimuli. Subsequently, it elaborates on the role of these smart hydrogels in antibacterial, anti-inflammatory, immunomodulatory, and tissue regeneration therapies. Additionally, it explores the challenges faced by smart hydrogels during clinical translation. By integrating disease mechanisms, material design principles, and therapeutic function regulation, this review aims to provide guidance for the development of smart hydrogel systems for periodontal therapy.
    Keywords:  periodontitis; smart hydrogel; stimulus response; tissue regeneration
    DOI:  https://doi.org/10.1177/19373368261486381
  57. Cell Rep. 2026 Sep 15. pii: S2211-1247(26)01061-2. [Epub ahead of print]45(9): 117983
    Molecular mimicry and functional convergence of bacterial proteins in host-microbe interactions.
    Amna Chudhary, Xiaoyun Wang.
      Bacterial proteins modulate host immunity through diverse molecular strategies that are often broadly described as molecular mimicry. However, inconsistent terminology has obscured distinctions between genuine host-like interactions and other forms of host-directed immune modulation. We propose an operational framework that classifies bacterial proteins into four mechanistic categories: molecular mimicry, mimic-like behavior, functional convergence, and pathway interference. The framework prioritizes explicit criteria, including host-target engagement, interaction-interface similarity, functional equivalence, predominant molecular mechanism, and strength of supporting evidence, rather than immune outcome alone. Representative bacterial effectors are discussed alongside their evolutionary origins, computational prediction, experimental validation, and emerging technologies for mechanistic investigation. By separating evolutionary processes from molecular action and applying evidence-based classification criteria, this review clarifies ambiguous terminology and provides a consistent conceptual foundation for interpreting bacterial immune modulation. The framework may also guide future mechanistic studies, comparative analyses, and translational research across diverse pathogenic and commensal host-microbe interaction systems.
    Keywords:  CP: microbiology; functional convergence; host-microbe interactions; immune modulation; microbiome; molecular mimicry
    DOI:  https://doi.org/10.1016/j.celrep.2026.117983
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