bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–05–10
forty-five papers selected by
Luca Bolliger, lxBio
  1. Phage Therapy as an Alternative Strategy Against Pseudomonas aeruginosa: A Narrative Review of Preclinical and Clinical Evidence.
  2. From hype to hope: reanimating phage therapy through evidence-based multidisciplinarity.
  3. Multiomics Approaches for Bacteriophage-Based Biocontrol Applications: A Review of Metabolomics, Transcriptomics, and Proteomics.
  4. Meta-analysis of preclinical evidence supporting phage therapy against Stenotrophomonas maltophilia.
  5. The building blocks of phage therapy: from lytic phage identification to preclinical validation against antimicrobial-resistant critical priority bacteria.
  6. Phage Therapy in Gastrointestinal Diseases: Current Status and Challenges.
  7. Antibiotic resistant Achromobacter xylosoxidans are highly susceptible to bacteriophages and often are killed synergistically by phage/antibiotic combinations.
  8. Short-term antagonism between bacteriophages and macrophages decreases with bacteria-phage coevolution.
  9. Integrated Morphological, Functional, and Genomic Analysis of a Novel Lytic Phage (VIT_AJPSC) Infecting Multidrug-Resistant Shigella dysenteriae.
  10. Antibacterial Efficacy of Pseudomonas aeruginosa Bacteriophages on a Drosophila Infection Model.
  11. Periodontal Disease and Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis of Risk and Survival Outcomes.
  12. Isolation and characterization of broad-range Staphylococcus epidermidis sepunaviruses.
  13. Newly isolated Pakpunavirus: efficacy and safety assessment in light of alternative therapies against P. aeruginosa skin infections.
  14. Maintenance Debridement in Chronic Hard-to-Heal Wounds: Toward Dynamic Homeostasis and Precision Intervention.
  15. Isolation and Characterization of Clostridioides difficile Bacteriophages.
  16. Gut microbiota and uveitis: exploring novel mechanisms of inflammatory ocular diseases via the gut-eye axis.
  17. Cutting-Edge Smart Hydrogel Platforms for Improved Wound Healing.
  18. Artificial intelligence in periodontal disease research: a bibliometric and visualized analysis of global research trends (2007-2025).
  19. New Insights into Acinetobacter baumannii Pathogenesis and Therapeutic Implications.
  20. Targeted autophagy: research progress on the regulatory potential of periodontitis prevention and treatment.
  21. Adjuvant multisite bacteriophage cocktail administration as salvage treatment in a patient with a multidrug-resistant Pseudomonas aeruginosa frontal relapsing complex osteitis.
  22. Bacterial extracellular vesicles in the oral-gut axis: Roles in periodontitis and inflammatory bowel disease.
  23. Oral-Gut Microbiome Axis in Crohn's Disease: A Potential Role of Ectopic Colonization.
  24. The oral-vascular axis: immune mechanisms linking periodontal dysbiosis to systemic vascular pathology.
  25. Efficacy of a Salmonella Bacteriophage Cocktail Against Multidrug-Resistant Salmonella Isolates From Clinical and Food Samples.
  26. The Wound Healing: A Mystery Still to Be Solved-What Is the Future?
  27. The Silent Link: Exploring the Impact of Periodontal Diseases on Head and Neck Carcinogenesis.
  28. Eco-evolutionary responses to plasmid-dependent phage constrain the spread of multidrug resistance plasmids.
  29. A DPP inhibitor suppresses periodontitis via antibacterial effect targeting Porphyromonas gingivalis.
  30. Challenges and future directions in AI-driven biomaterials for microbiome-associated oral infectious diseases: A systematic review.
  31. Exploring the oral microbiome: from traditional techniques to advanced omics and databases.
  32. Isolation and Characterization of Two Bacteriophages Infecting Bacillus anthracis: Biological Properties and Genomic Analysis.
  33. Bioactive wound dressings for diabetic foot ulcers: Mechanisms, materials, and clinical translation.
  34. Periodontitis and Pancreatic Cancer Risk: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.
  35. ICP1 bacteriophage treatment antagonizes colonization of the zebrafish larval intestine by Vibrio cholerae.
  36. Canadian Patient Perspectives on Facilitators and Barriers to Diabetic Foot Ulcer Care: A Scoping Review.
  37. Cryo-EM structures of prevalent gut phage PD491P1 uncover extensive disulfide stabilization and distinct structural adaptations.
  38. Engineering a T7 bacteriophage to attenuate LPS-driven inflammatory responses during bacteriolysis.
  39. Clinical Profile, Risk Factors, and Microbial Dysbiosis in Periodontitis: Findings from an Adult Cohort and Microbiome-Based Predictive Models.
  40. Periodontitis and Chronic Liver Disease: Mechanistic Insights Focusing on Porphyromonas gingivalis-A Narrative Review.
  41. Isolation and characterization of a therapeutic lytic phage cocktail against mastitis-associated Enterococcus faecalis with antibiofilm activity and in vivo efficacy.
  42. Immunopathogenic insights into members of the class Bunyaviricetes: a comparative review of emerging zoonotic threats.
  43. Discovering New Jumbo Phage Biology with Cryo-Electron Microscopy.
  44. Age-Related Differences in Oral Microbiota Among Obese Patients with Periodontitis: A Systematic Review.
  45. Local Antibiotic-Loadable Carriers for the Treatment of Chronic Osteomyelitis: A Narrative Review.
  1. Microbiologyopen. 2026 Jun;15(3): e70303
    Phage Therapy as an Alternative Strategy Against Pseudomonas aeruginosa: A Narrative Review of Preclinical and Clinical Evidence.
    Gustavo Aparecido da Cunha, Raine Piva Amaral, Ana Luisa Cauvila Dos Santos, Bárbara Rafaela Ferreira Aio, Maria Fernanda Romboli Durante, Luiz Cosme Cotta Malaquias, Gabriel Magno de Freitas Almeida, Luiz Felipe Leomil Coelho.
      Pseudomonas aeruginosa is an opportunistic pathogen and one of the main causes of nosocomial infections. This pathogen affects immunocompromised individuals such as patients with chronic wounds or cystic fibrosis. Its capacity to evade antimicrobial therapies through resistance mechanisms has resulted in widespread prevalence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) strains. We searched three databases (PubMed/Medline, Scopus, and Web of Science) for articles evaluating the effects of phage administration in the management of P. aeruginosa infections in animals and humans. We analyzed the main characteristics of the interventions, the coverage of different bacterial strains, and discussed possible gaps in the evidence available in the last 10 years. Literature shows strong evidence that the use of phage therapy for several clinical conditions in humans and animal models is a safe and effective intervention for infections caused by MDR/XDR/PDR P. aeruginosa. Despite its therapeutic potential, phage therapy still faces several limitations such as lack of standardized dosing protocols, inconsistent endotoxin quantification, and limited regulatory frameworks. Future guidelines should focus on the regulation and validation of phage therapy in clinical practice, after overcoming the limitations currently identified. Further studies should ensure the standardization of phage production and the validation of delivery systems and routes of administration. Conducting multicenter clinical trials can contribute to the clinical implementation of phage therapy in countries where it is not yet regulated.
    Keywords:  Pseudomonas aeruginosa; antimicrobial resistance; bacteriophage; multi‐drug‐resistance; phage therapy
    DOI:  https://doi.org/10.1002/mbo3.70303
  2. Nat Commun. 2026 05 07. pii: 4107. [Epub ahead of print]17(1):
    From hype to hope: reanimating phage therapy through evidence-based multidisciplinarity.
    Aleksandra Petrović-Fabijan, Stephen T Abedon.
      Phage therapy must move beyond anecdote to clinical reproducibility. Despite compelling cases of bacteriophages curing otherwise untreatable infections, inconsistent outcomes and biological complexity continue to limit clinical adoption. Here we identify three foundational pillars-drug delivery, treatment effectiveness, and managing bacterial resistance that must be addressed through interdisciplinary collaboration to transform phage therapy from a niche intervention to a powerful weapon against antimicrobial resistance. The time for rigorous, translational phage science is now.
    DOI:  https://doi.org/10.1038/s41467-026-72590-7
  3. Biomed Res Int. 2026 ;2026(1): e8304153
    Multiomics Approaches for Bacteriophage-Based Biocontrol Applications: A Review of Metabolomics, Transcriptomics, and Proteomics.
    Daniel Jesuwenu Ajose, Collins Njie Ateba.
      The emergence of multidrug-resistant (MDR) in various microorganisms due to prolonged antibiotic treatment poses a growing worldwide health issue. It is essential to identify alternative, effective methods to address MDR bacterial diseases, as treating infections caused by these pathogens can be challenging. Bacteriophages, also known as phages, are viruses that target and destroy bacteria. They are being investigated and utilized as alternatives to existing therapies because of their effectiveness and specificity. Phages are often considered safe substitutes for antibiotics because they naturally occur in the environment. Phage replacement therapy involves complex biological processes driven by interactions between phages and bacteria. An integrative approach is essential for a comprehensive analysis of these processes and for understanding the relationships between different biomolecules and their functions. This includes combining data from various omics, such as transcriptomics, proteomics, and metabolomics. High-throughput technology has revolutionised research, enabling the development of numerous tools and methods for integrating and interpreting multiomics data from diverse samples. This paper presents an overview of omics technologies and highlights strategies for integrating them across layers. By comparing data from multiomics and single-omics studies, a deeper understanding of the information flow underlying phage therapy will be gained.
    Keywords:  antibiotics; bacteria–phage interaction; drug resistance; multiomics; next-generation sequencing; phage therapy
    DOI:  https://doi.org/10.1155/bmri/8304153
  4. Future Microbiol. 2026 Apr;21(5): 483-491
    Meta-analysis of preclinical evidence supporting phage therapy against Stenotrophomonas maltophilia.
    Hamid Sadeghi, Saeideh Gholamzadeh Khoei, Amir Javadi, Mehdi Bakht, Masoumeh Aslanimehr, Farhad Nikkhahi.
       AIM: To systematically and quantitatively assess the efficacy of phage therapy against multidrug-resistant Stenotrophomonas maltophilia in preclinical models.
    MATERIALS AND METHODS: A systematic search of PubMed, Scopus, ScienceDirect, Google Scholar, and Wiley Online Library was conducted for preclinical studies on phage therapy against established S. maltophilia infections with survival outcomes. Data were pooled using a fixed-effects model, with subgroup and sensitivity analyses.
    PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD420251059693.
    RESULTS: Among 6,277 references, six studies met the inclusion criteria; one study was excluded after sensitivity analysis. The overall pooled Odds Ratio (OR) for phage therapy efficacy was 21.10 (95% CI: 9.09-49.02; p < 0.001). Subgroup analysis by Multiplicity of Infection (MOI) showed dose-dependent effects, with the highest efficacy at MOI = 100 (OR =143.68, 95% CI: 11.95-1726.78; p < 0.001) followed by MOI = 10 (OR =60.13, 95% CI: 6.29-575.09; p < 0.001). Burst size analysis indicated larger burst sizes increased effect magnitude, with the highest at 41.67 (OR =31.27, 95% CI: 7.32-133.49; p < 0.001).
    CONCLUSION: Phage therapy shows strong preclinical efficacy against multidrug-resistant S. maltophilia. It represents a rapid, targeted, and antibiotic-sparing approach, supporting future antimicrobial stewardship efforts and informing the design of clinical applications.
    Keywords:  Stenotrophomonas maltophilia; meta-analysis; multidrug-resistant bacteria; phage therapy; preclinical animal models
    DOI:  https://doi.org/10.1080/17460913.2026.2667121
  5. Microbiol Spectr. 2026 May 04. e0050726
    The building blocks of phage therapy: from lytic phage identification to preclinical validation against antimicrobial-resistant critical priority bacteria.
    Filipa F Vale.
      The fight against antimicrobial resistance is bringing back phage therapy, consisting of the use of lytic phages against specific pathogenic bacteria. For this purpose, libraries of well-characterized lytic phages are crucial, as the phage-bacteria arms race can limit efficacy, making phage cocktails generally more effective. In a recent study by H. -Y. Kuo, C. J. B. Bregente, T. T. D. Thuy, J. H. Hidrosollo, et al. (Microbiol Spectr 13:e00835-25, 2025, https://doi.org/10.1128/spectrum.00835-25), 12 novel lytic phages were isolated against carbapenem-resistant Enterobacter cloacae complex, a WHO critical-priority pathogen. These phages showed antibacterial activity in vitro and a broad host range across a panel of 80 CR-ECC isolates, as well as improved survival in the invertebrate model Galleria mellonella. Testing the two most promising phages in a mouse model showed that one significantly enhanced survival, demonstrating its therapeutic potential. This study offers a roadmap for isolating, characterizing, and evaluating phages for therapeutic use.
    Keywords:  Enterobacter; Enterobacter cloacae complex; antibiotic resistance; bacteriophage therapy
    DOI:  https://doi.org/10.1128/spectrum.00507-26
  6. Int J Mol Sci. 2026 Apr 20. pii: 3662. [Epub ahead of print]27(8):
    Phage Therapy in Gastrointestinal Diseases: Current Status and Challenges.
    Shaokun Zhang, Ying Zhang.
      A phage is a virus that targets bacteria with high precision. While phage therapy provides a targeted alternative to broad-spectrum antibiotics, it is not completely free from the challenges of antimicrobial resistance, as phages can facilitate the horizontal transfer of resistance genes through transduction and promote the growth of phage-resistant strains. Nonetheless, within the One Health framework, the strategic use of phages remains a vital and promising tool for addressing the global antimicrobial resistance crisis. This paper reviews current research on phage therapy for gastrointestinal diseases such as cirrhosis, enteritis, and Helicobacter pylori infection. It also details how phages help regulate gut microecological balance and discusses how phage dysbiosis can lead to innate immune dysfunction and worsen conditions like inflammatory bowel disease. The review summarizes both the therapeutic potential and limitations observed in clinical trials and fundamental studies. Transitioning from laboratory research to clinical practice is hindered by multiple complex challenges, including the stomach's extreme acidity, physical entrapment by the intestinal mucus layer, the rapid co-evolution of bacterial resistance, and ecological risks associated with temperate phages. To overcome challenges like gastrointestinal barrier tolerance and address ethical, technical, and practical hurdles for clinical use, the paper outlines treatment strategies for specific conditions and highlights future directions, providing guidance for employing phages in digestive system disease management. These future innovations focus on integrating artificial intelligence-driven precision matching, advanced bioengineering for durable delivery systems, and multimodal combination therapies to safely modulate the intestinal microecology.
    Keywords:  clinical translation; gastrointestinal diseases; gut microecology; phages
    DOI:  https://doi.org/10.3390/ijms27083662
  7. Res Sq. 2026 Apr 30. pii: rs.3.rs-9371970. [Epub ahead of print]
    Antibiotic resistant Achromobacter xylosoxidans are highly susceptible to bacteriophages and often are killed synergistically by phage/antibiotic combinations.
    Ana Cobián Güemes1
      Achromobacter infections pose significant challenges to people with Cystic Fibrosis (CF). This microbe often becomes multidrug resistant (MDR) or extensively drug resistant (XDR), leaving physicians with few antibiotic treatment options. It is a growing problem in people with CF because it is difficult to eliminate with antibiotics, leading to chronic lung infections that increasingly acquire antibiotic resistance. We have been searching for alternative therapies for Achromobacter infection and identified a cadre of 26 bacteriophages (viruses that attack bacteria) that target it that could allow us to reduce reliance on antibiotics. We tested these phages against a collection of 56 MDR and XDR clinical Achromobacter isolates and found that all were susceptible to multiple of these phages. We also evaluated whether we could restore the activity of certain antibiotics by using them as adjunctive therapy to phage treatment in vitro. We found that when meropenem (a beta lactam antibiotic) was added to phage treatment, susceptibility to meropenem was demonstrated in many isolates regardless of whether the Achromobacter was initially susceptible to meropenem. The data presented here suggests that combination therapy using meropenem with an active phage should be considered for treatment of Achromobacter infections regardless of pre-existing antibiotic susceptibility.
    DOI:  https://doi.org/10.21203/rs.3.rs-9371970/v1
  8. ISME J. 2026 May 08. pii: wrag116. [Epub ahead of print]
    Short-term antagonism between bacteriophages and macrophages decreases with bacteria-phage coevolution.
    Meaghan Castledine, Zuzanna Szczutkowska, Andrew Matthews, Sarah K Walsh, Rai Lewis, Suzanne Kay, Janet A Willment, Gordon D Brown, Angus Buckling.
      Phage therapy, the use of viruses that infect bacteria (bacteriophages), is a promising complement to antibiotics during the antimicrobial resistance crisis, but treatment success is very variable. A key variable which likely influences treatment outcomes is how different immune components interact with bacteriophage, with studies finding neutrophils work synergistically while macrophages work antagonistically with bacteriophage. However, many of these studies characterise interactions and outcomes over short timescales, not considering the potential for the evolution of resistance to bacteriophages which can itself greatly affect treatment outcomes. Here, we measure how macrophages and bacteriophages affect densities and resistance evolution of the pathogen Pseudomonas aeruginosa in vitro. Consistent with previous studies, we find macrophages interact antagonistically with bacteriophages in the short term. However, this antagonism was lost following bacterial population recovery associated with rapidly evolved resistance to bacteriophages. Macrophages resulted in greater net levels of resistance and hindered increases in bacteriophage infectivity, but this did not lead to differences in bacteria-phage population dynamics. This work emphasises the importance of characterising the effect of the immune system on phage therapy outcomes over both shorter- and longer- timescales.
    Keywords:  Pseudomonas aeruginosa; bacteriophages; experimental evolution; immune system; macrophages; phage therapy
    DOI:  https://doi.org/10.1093/ismejo/wrag116
  9. Braz J Microbiol. 2026 May 06. pii: 135. [Epub ahead of print]57(1):
    Integrated Morphological, Functional, and Genomic Analysis of a Novel Lytic Phage (VIT_AJPSC) Infecting Multidrug-Resistant Shigella dysenteriae.
    Aishwarya Srivastava, Jayaprakash N S.
      Bacteria are historically known to cause a disproportionate number of deaths because of infectious diseases worldwide. Annually, 55 million deaths are accounted for because of bacterial infections, out of which approximately 3 million deaths are because of diarrhoea and dysentery. Shigellosis is an infectious disease caused by Shigella species, and it targets the intestinal tract. It is characterised by acute diarrhoea mixed with blood. The oral antibiotics recommended for shigellosis are ciprofloxacin and azithromycin, with ciprofloxacin as the first-line treatment. Recently, Shigella species have shown a rapid increase in resistance to these antibiotics, which is leading to overdose and prolonged treatment for the same. There is a need of the hour to find a potential substitute for antibiotics. Many alternatives, such as antimicrobial peptides, plant-based substances, bacteriophages, and probiotics, have shown promise compared to antibiotics. This paper focuses on the isolation and characterization of bacteriophages against Shigella dysenteriae. Bacteriophages are viruses that kill bacteria and are very specific to their host. They require host machinery to replicate; therefore, there is very little chance of developing resistance in bacteria against phage. The paper describes screening and isolation of phages from environmental samples against Shigella dysenteriae, followed by optimization studies and their characterization, such as host range, burst size and one-step growth curve. Morphological characterization using transmission electron microscopy (TEM) and whole genome sequencing has been performed, indicating that the phage belongs to the Myoviridae family and has a genome size of 38kbp.
    Keywords:  Antibiotic resistance; Antibiotics; Bacterial infections; Bacteriophage therapy; Shigellosis
    DOI:  https://doi.org/10.1007/s42770-026-01947-3
  10. Pathogens. 2026 Apr 10. pii: 411. [Epub ahead of print]15(4):
    Antibacterial Efficacy of Pseudomonas aeruginosa Bacteriophages on a Drosophila Infection Model.
    Karel Petrzik, Sára Brázdová.
      Pseudomonas aeruginosa is a widespread pathogen that causes acute and chronic diseases in various organisms, including humans. Treating this antibiotic-resistant bacterium is challenging, so alternative or supplementary treatment strategies are desirable. Six novel bacteriophages specific to P. aeruginosa were isolated and classified into the genera Septimatrevirus, Kochitakasuvirus, Bruynoghevirus, and a new, unnamed genera related to Napahavirus, and Kantovirus. Their genomes were annotated and further characterized. We used the Drosophila melanogaster insect model to predict the efficacy of the phages in terms of their curative function on other organisms. Flies were chronically infected by feeding them bacteria and were subsequently treated with individual bacteriophages. The results of the Kaplan-Meier survival test revealed differences in phage efficacy and supported the hypothesis that the phages had a curative effect. These mentioned phages extended the flies' lifespan.
    Keywords:  Pseudomonas aeruginosa; animal model; chronic infection; new virus genus; phagotherapy
    DOI:  https://doi.org/10.3390/pathogens15040411
  11. J Clin Med. 2026 Apr 21. pii: 3161. [Epub ahead of print]15(8):
    Periodontal Disease and Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis of Risk and Survival Outcomes.
    Gabriela Guadalupe Zambrano Manzaba, Luis Chauca-Bajaña, Carlos Andrés Guim Martínez, Sara Isabel Marcalupo Llerena, Andrea Ordoñez Balladares, Byron Velasquez Ron, Carlos Enrique Cuevas-Suárez, Abigailt Flores-Ledesma, Veronica Natalia Maroto Hidalgo, Gina Fernanda Vásquez Armas.
      Background/Objectives: Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies and remains associated with substantial global morbidity and mortality. Although tobacco and alcohol are established risk factors, they do not fully explain OSCC incidence, highlighting the need to explore additional contributors such as chronic inflammatory conditions. Periodontal disease, characterized by persistent inflammation and microbial dysbiosis, has emerged as a plausible factor in oral carcinogenesis and tumor progression. To systematically evaluate the association between periodontal disease and the risk of developing OSCC, and to assess the prognostic impact of periodontal disease-related factors, particularly intratumoral Porphyromonas gingivalis, on survival outcomes in patients with OSCC. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and prospectively registered in PROSPERO (CRD420261296479). Comprehensive searches were performed in PubMed, EMBASE, Web of Science, Scopus, the Cochrane Library, ClinicalTrials.gov, and World Health Organization regional databases. Case-control studies evaluating OSCC risk and cohort studies assessing survival outcomes were included. Random-effects meta-analyses using inverse-variance models were applied. Heterogeneity was assessed using the I2 statistic, and robustness was evaluated through Hartung-Knapp adjustment, leave-one-out sensitivity analyses, and Trial Sequential Analysis. Results: Five case-control studies were included in the etiological analysis. Periodontal disease was significantly associated with an increased risk of OSCC (pooled OR = 3.17; 95% CI: 1.94-5.21), with moderate heterogeneity (I2 = 58.7%). Two cohort studies were included in the prognostic analysis. High intratumoral expression of P. gingivalis was significantly associated with poorer overall survival (pooled HR = 2.15; 95% CI: 1.33-3.47), with no detected heterogeneity (I2 = 0%). Conclusions: Periodontal disease is strongly associated with an increased risk of OSCC, and intratumoral P. gingivalis appears to be an adverse prognostic marker. These findings underscore the relevance of periodontal inflammation and microbial factors across the OSCC continuum, from carcinogenesis to clinical outcomes, and support their consideration as potential targets for risk stratification and prevention strategies.
    Keywords:  Porphyromonas gingivalis; carcinoma; mouth neoplasms; periodontal diseases; squamous cell; survival analysis
    DOI:  https://doi.org/10.3390/jcm15083161
  12. Microbiology (Reading). 2026 May;172(5):
    Isolation and characterization of broad-range Staphylococcus epidermidis sepunaviruses.
    Carlos Valdivia, Callum O Rimmer, Jonathan C Thomas, David Negus, Pilar Domingo-Calap.
      Staphylococcus epidermidis is a major contributor to biofilm-associated infections, bacteraemia and sepsis in humans. Additionally, it is an important veterinary pathogen. The spread of multi-drug resistant S. epidermidis poses an even greater challenge, requiring the development of antibiotic-alternative approaches. Here, we isolated four new broad-range phages capable of infecting a large panel of 65 clinical and veterinary isolates of S. epidermidis. Phages with the broadest host range produced plaques on 37% of the hosts tested and halos on an additional 40%. These phages belonged to the Sepunavirus genus, as supported by their morphology and genome analysis. A genome-wide association study identified a significant correlation between resistance to phage lysis and the presence of the ppl defence system and the ica operon, highlighting the protective role of biofilms against the phages isolated in this study. Furthermore, distinct phage-encoded methyltransferases identified in the phage genomes may contribute to differences in host ranges. This study advances our knowledge on the diversity and characteristics of S. epidermidis phages, which could be considered as interesting tools for phage therapeutics.
    Keywords:  Staphylococcus epidermidis; biofilm; phages; sepunaviruses
    DOI:  https://doi.org/10.1099/mic.0.001693
  13. Front Microbiol. 2026 ;17 1807725
    Newly isolated Pakpunavirus: efficacy and safety assessment in light of alternative therapies against P. aeruginosa skin infections.
    Agnieszka Necel, Małgorzata Stasiłojć, Wojciech Wesołowski, Magdalena Narajczyk, Katarzyna Kosznik-Kwaśnicka, Natalia Kaźmierczak, Łukasz Naumiuk, Hanna Loika, Lidia Piechowicz, Anna Żywicka.
      Pseudomonas aeruginosa is the major cause of hospital-acquired infections and morbidity and mortality in individuals with burn wounds, due to the emergence of antibiotic resistance. As a result, some scientists are concentrating on research for alternative treatment, with phage therapy being one of the suggestions. However, a thorough description of the phages under consideration for use is necessary to optimize the treatment process. Thus, we show in this paper that the newly isolated phage vB_Pa_AN-12, member of the Pakpunavirus genus, is a perfect fit for phage therapy. It can infect several clinical strains of P. aeruginosa, including those resistant to multiple antibiotics. It is also able to decrease the viability of host cells strain by 5 logs in 1 h. Furthermore, it does not carry any harmful genes, and has efficient intracellular development with about 100 progeny virions per infected cell. Additionally, it did not affect the viability of cell lines that represented keratinocytes (HaCaT), fibroblasts (BJ), and monocytes (SC). These results suggest that usage of this phage, especially for skin infections, won't cause any side effects resulting from phage-human cell interactions. Nevertheless, given there is a possibility of phage resistance development, the action of isolated phage should be further investigated in combinations with other antimicrobials.
    Keywords:  Pakpunavirus; Pseudomonas aeruginosa; antimicrobial resistance; phage therapy; skin infections
    DOI:  https://doi.org/10.3389/fmicb.2026.1807725
  14. Int Wound J. 2026 May;23(5): e70930
    Maintenance Debridement in Chronic Hard-to-Heal Wounds: Toward Dynamic Homeostasis and Precision Intervention.
    RuoDi Lu, Yi Zhang, Biao Cheng.
      Debridement is widely used across various wound types, but its biological significance differs fundamentally between acute and chronic hard-to-heal wounds. In acute wounds, debridement directly triggers the initiation of regeneration; however, in chronic wounds, persistent biofilm, insufficient angiogenesis and dysregulated inflammation lead to a prolonged cycle of inflammation and proliferation, making traditional one-off debridement insufficient to change the healing trajectory. Therefore, the concept of debridement needs to evolve from an acute wound model to a sequential, biologically driven continuous management strategy. Maintenance debridement, by dynamically regulating the microenvironment, reducing pathological load and restoring a 'healable state', has emerged as the crucial bridge between inflammation control and regenerative therapies. This review systematically explains the theoretical basis and clinical value of maintenance debridement and explores the future direction of AI-assisted precision debridement management.
    DOI:  https://doi.org/10.1111/iwj.70930
  15. Methods Mol Biol. 2026 ;3046 57-81
    Isolation and Characterization of Clostridioides difficile Bacteriophages.
    Alexia L M Royer, Andrew A Umansky, Louis-Charles Fortier.
      Bacteriophages, or simply phages, are viruses that infect bacteria. They are the most abundant biological entity on Earth and their impact on the physiology and evolution of bacteria is tremendous. Phages have been at the forefront of developments in molecular biology and genetics. With the rise in antibiotic resistance worldwide, they are now also viewed as powerful antimicrobials to fight multidrug-resistant pathogens. Several methods have been developed over decades of fundamental phage research to work with phages. Although some of these methods are readily applicable to most phages, others need to be specifically adapted to a given phage-host ecosystem. For example, Clostridioides difficile is a strict anaerobe and methods that are normally performed on the open bench need to be done inside an anaerobic chamber, which complicates working with phages. Phage propagation in liquid and on solid agar can also be influenced by different parameters such as the concentration of agar or agarose and the presence of divalent cations. Our lab has 20 years of experience working with C. difficile phages and this chapter describes basic methods that we use to isolate, purify, propagate, and characterize phages infecting C. difficile.
    Keywords:  Bacteriophage isolation and propagation; Prophage induction; Prophage prediction tool
    DOI:  https://doi.org/10.1007/978-1-0716-5328-9_5
  16. Front Microbiol. 2026 ;17 1749111
    Gut microbiota and uveitis: exploring novel mechanisms of inflammatory ocular diseases via the gut-eye axis.
    Qing Gao, Meng Xiong, Shunhua Zhou, Jing Lu, Baoping Ren, Qinghua Peng, Meiyan Zeng, Houpan Song.
      Uveitis is an inflammatory ocular condition that primarily affects young adults and is often associated with systemic and autoimmune disorders. This disease primarily affects intraocular structures such as the iris, ciliary body, and choroid. Clinically, it manifests through a series of symptoms, including eye redness, pain, and blurred vision, which significantly impact the quality of life for patients worldwide. Recently, the role of gut microbiota (GM) in the immune regulation and pathogenesis of inflammatory diseases has garnered significant scientific interest. This study aimed to investigate the potential association between GM and uveitis, with the objective of demonstrating novel mechanisms underlying inflammatory ocular diseases through the emerging concept of the "gut-eye axis." Current research suggests that gut dysbiosis may influence the immune status of distal organs via various pathways, including molecular mimicry, modulation by microbial metabolites, disruption of intestinal immune homeostasis, and compromise of the intestinal mucosal barrier. Building on these mechanisms, we further explored innovative therapeutic strategies targeting GM and its metabolites, including probiotics, prebiotics, antibiotics, immunomodulators, phage therapy, fecal microbiota transplantation, and dietary interventions. This review systematically examined the association between GM dysbiosis and uveitis pathogenesis, offering new insights and directions for future research in this emerging field and establishing a theoretical foundation for developing targeted therapies based on the modulation of the microbiome.
    Keywords:  gut microbiota; gut-eye axis; pathogenesis; treatment; uveitis
    DOI:  https://doi.org/10.3389/fmicb.2026.1749111
  17. Pharmaceutics. 2026 Mar 25. pii: 406. [Epub ahead of print]18(4):
    Cutting-Edge Smart Hydrogel Platforms for Improved Wound Healing.
    Ameya Sharma, Vivek Puri, Divya Dheer, Malkiet Kaur, Kampanart Huanbutta, Tanikan Sangnim.
      Background/Objectives: Wound management presents a substantial clinical challenge due to the rising incidence of chronic wounds, infections, and the limitations of conventional dressings in creating an ideal healing microenvironment. This review aims to provide a comprehensive overview of advanced smart hydrogel platforms designed to improve wound healing outcomes, focusing on their capacity to respond adaptively to physiological and external stimuli. Methods: This article analyzes the core characteristics of smart hydrogels, specifically examining stimuli-responsive systems (pH, temperature, enzyme, light, and electricity). The review evaluates advanced configurations-including injectable, self-healing, and 3D-printable systems-and functionalized hydrogels integrated with antimicrobials, drugs, and nanocomposites. Additionally, essential characterization methodologies, biological assessments, and regulatory considerations for clinical translation are synthesized. Results: The literature, which is predominantly preclinical in nature, indicates that functionalized hydrogels significantly enhance tissue regeneration, angiogenesis, and infection control compared to traditional methods. Conductive hydrogels utilizing bioelectrical signals show particular promise in accelerating the healing process. While current clinical applications and commercial products demonstrate efficacy, significant barriers remain regarding large-scale manufacturing and regulatory approval. Conclusions: Smart hydrogels represent a transformative approach to precision wound management, offering superior adaptability and therapeutic delivery. To achieve widespread clinical adoption, future research must address manufacturing scalability and focus on emerging trends, such as the integration of biosensors and AI-powered monitoring systems, to create fully intelligent wound care solutions.
    Keywords:  drug delivery system; nanomaterials; smart hydrogel; tissue engineering; wound healing
    DOI:  https://doi.org/10.3390/pharmaceutics18040406
  18. Saudi Dent J. 2026 May 07. pii: 63. [Epub ahead of print]38(5):
    Artificial intelligence in periodontal disease research: a bibliometric and visualized analysis of global research trends (2007-2025).
    Wuyan Zhou, Xun Liu, Jinghong Yu, Yaoxu Li, Lin Cheng, Guanliang Wang, Fulin Jiang.
      Periodontal disease is one of the most common diseases in stomatology. With the continuous development of artificial intelligence (AI), its integration with periodontology is rapidly evolving. However, a comprehensive bibliometric analysis mapping this interdisciplinary field is currently lacking. We conducted a bibliometric analysis by retrieving publications related to AI and periodontal disease from the Web of Science Core Collection (WoSCC) for the period January 2007 to July 2025. Data processing and visualization were performed using R (Bibliometrix), VOSviewer, and CiteSpace. A total of 496 relevant articles (437 research papers; 59 reviews) were included. Annual publication output has shown sustained growth, particularly since 2021. China contributed the most publications (153 articles), followed by the United States. Among institutions, Pusan National University, South Korea (32 articles), and Saveetha Institute of Medical and Technical Science, India (31 articles) were the most productive. BMC Oral Health published the highest number of articles (n = 23). The co-authorship network involved 2,604 authors, with Pradeep Kumar Yadalam being the most prolific (15 articles). Co-citation analysis identified Orhan Kaan, Abu Patricia Angela R., and Falk Schwendicke as the most cited authors. Keyword analysis revealed "periodontitis," "machine learning," and "artificial intelligence" as core research foci, while burst detection indicated "progression" and "expression" as emerging thematic directions. This study provides a systematic overview of the research landscape, highlighting evolving trends, key contributors, and knowledge structure in AI applications for periodontal disease. The findings offer valuable insights to help dentists and researchers understand current applications, identify frontiers, and potentially guide the future clinical translation of AI technologies in periodontology.
    Keywords:  Artificial intelligence; Bibliometrics; Periodontal disease; Trends
    DOI:  https://doi.org/10.1007/s44445-026-00160-0
  19. Pathogens. 2026 Apr 06. pii: 391. [Epub ahead of print]15(4):
    New Insights into Acinetobacter baumannii Pathogenesis and Therapeutic Implications.
    Rocco Morena, Helen Linda Morrone, Vincenzo Olivadese, Sara Palma Gullì, Francesca Serapide, Alessandro Russo.
      Acinetobacter baumannii is a leading cause of healthcare-associated infections and is classified among the highest-priority antimicrobial-resistant pathogens. Its clinical success reflects the convergence of antimicrobial resistance (AMR) and biological traits that promote environmental persistence and transmission. Acinetobacter baumannii has undergone a remarkable transformation over the past few decades, evolving from a relatively obscure environmental bacterium into a globally recognized multidrug-resistant pathogen. Its prevalence in healthcare settings, particularly intensive care units, has made it a leading cause of ventilator-associated pneumonia, bloodstream infections, wound infections, and urinary tract infections. Beyond its antibiotic resistance, the bacterium's ability to persist in hospital environments and adapt to host defences has amplified its clinical significance. Recent research has uncovered complex networks of virulence factors, regulatory systems, and metabolic strategies that enable A. baumannii to thrive in hostile environments and evade host immunity, providing new insights into its pathogenesis and potential therapeutic vulnerabilities. This review summarizes the main mechanisms underlying its pathogenicity, including desiccation tolerance, biofilm formation, disinfectant resistance, metal acquisition, motility, and the ability to enter viable but non-culturable states. In A. baumannii, AMR functions as a pathogenesis-adjacent trait, enhancing survival and clonal dissemination through genomic plasticity, resistance islands, efflux systems, and envelope remodeling. Key resistance pathways involve carbapenem-hydrolyzing oxacillinases, metallo-β-lactamases, permeability defects, and multidrug efflux, often coexisting within high-risk clones. From a clinical perspective, management of carbapenem-resistant strains requires accurate infection diagnosis, reliable susceptibility testing, site-specific and PK/PD-optimized therapy, and early reassessment. Overall, the success of A. baumannii reflects the integration of resistance and persistence within healthcare ecosystems, highlighting the need for coordinated strategies combining stewardship, infection control, improved diagnostics, and anti-biofilm or anti-virulence approaches.
    Keywords:  Acinetobacter baumannii; biofilm; carbapenem resistance; multidrug resistance; virulence factors; β-lactam-β-lactamase inhibitors
    DOI:  https://doi.org/10.3390/pathogens15040391
  20. Front Cell Dev Biol. 2026 ;14 1708337
    Targeted autophagy: research progress on the regulatory potential of periodontitis prevention and treatment.
    Yujia Wang, Zhaojiang Fu, Yingtao Wu.
      Chronic periodontitis is a multifactorial inflammatory disease primarily caused by bacterial pathogens, leading to progressive destruction of both soft and hard periodontal tissues. While dental plaque biofilm has been universally recognized as the primary etiological factor in periodontitis development, disease progression is also influenced by local irritants and systemic modulators, making its pathogenesis complex and widely studied. Autophagy, an essential cellular self-protection mechanism, plays a pivotal role in maintaining intracellular homeostasis, responding to stress stimuli, and defending against microbial invasion. Recently, this process has emerged as a key research focus in periodontal pathology. This study investigates the dynamic changes and functional variations of autophagy during different stages of periodontitis, aiming to elucidate its precise role in disease initiation and progression.
    Keywords:  Porphyromonas gingivalis; autophagosome; autophagy; chronic periodontitis; mTOR
    DOI:  https://doi.org/10.3389/fcell.2026.1708337
  21. Int J Infect Dis. 2026 May 01. pii: S1201-9712(26)00391-7. [Epub ahead of print] 108756
    Adjuvant multisite bacteriophage cocktail administration as salvage treatment in a patient with a multidrug-resistant Pseudomonas aeruginosa frontal relapsing complex osteitis.
    Aurore Denis, Tristan Ferry, Franck Jegoux, Tiphaine Menez, Thomas Briot, Rafael Gomes, Cindy Fevre, Alexia Le Corre, Matthieu Revest, David Luque Paz.
       BACKGROUND: Bone infection due to multidrug-resistant (MDR) Pseudomonas aeruginosa is associated with poor outcomes, especially high risk of relapses. Adjunctive multisite phage therapy can be used as a salvage treatment in relapsing cases.
    CASE PRESENTATION: We treated a 37-year-old man with MDR P. aeruginosa frontal osteitis and a large frontal fistula, who experienced three relapses, using personalized multisite phage therapy combined with surgery and prolonged antibiotics (ceftolozane/tazobactam). The multisite phage administration included in situ instillation of the manufactured phage cocktail during surgery, followed by daily intravenous infusion and nebulization for seven days after surgery. No adverse events were reported during treatment. At the two-year follow-up, the patient had no relapse without any suppressive treatment.
    CONCLUSION: Multisite phage administration is a personalized treatment strategy that can prevent relapse or the emergence of additional antimicrobial resistance in complex cases, such as relapsing MDR P. aeruginosa osteitis.
    DOI:  https://doi.org/10.1016/j.ijid.2026.108756
  22. Microbiol Res. 2026 Apr 23. pii: S0944-5013(26)00098-4. [Epub ahead of print]309 128534
    Bacterial extracellular vesicles in the oral-gut axis: Roles in periodontitis and inflammatory bowel disease.
    Jiyan He, Huan Hu, Yunzhuo Huang, Bing Xu, Jieru Yang, Wenfei Lv, Miao Wang, Qunli Ren, Xiaolan Li, Yonghao Zhu, Kun Wang, Qian Wang.
      The oral-gut axis links the oral and gut microbiomes, both anatomically and functionally, and its dysregulation is implicated in periodontitis and inflammatory bowel disease (IBD). Bacterial extracellular vesicles (BEVs), nano-sized particles (20-250 nm) released by diverse microbes, serve as key mediators of inter-organismal communication along this axis. Carrying virulence factors, nucleic acids, and immunomodulators, BEVs influence microbial ecology and host immunity. In the oral cavity, pathogen-derived BEVs (e.g., from Porphyromonas gingivalis) promote biofilm formation, immune evasion, and tissue destruction. In the gut, BEVs from commensals (e.g., Akkermansia muciniphila) reinforce barrier function and suppress inflammation, whereas those from pathogens exacerbate dysbiosis. Critically, BEVs mediate bidirectional crosstalk: oral pathogen BEVs can translocate to the gut and worsen IBD, while beneficial gut-derived BEVs may attenuate periodontal inflammation. This review summarizes the roles of BEVs in oral-gut communication, their involvement in inflammatory disease pathogenesis, and their potential as biomarkers and therapeutics.
    Keywords:  Bacterial extracellular vesicles (BEVs); Dysbiosis; Gut barrier; Immune modulation; Inflammatory bowel disease (IBD); Oral-gut axis; Periodontitis
    DOI:  https://doi.org/10.1016/j.micres.2026.128534
  23. Microorganisms. 2026 Apr 02. pii: 810. [Epub ahead of print]14(4):
    Oral-Gut Microbiome Axis in Crohn's Disease: A Potential Role of Ectopic Colonization.
    Ceren Ozkul, Emre Duman, Engin Kocak, Yalcin Tarkan Karakan, Can Cindoruk, Odul Egritas Gurkan, Mehmet Cindoruk, Tarkan Karakan.
      Recently, an oral-gut communication axis has been proposed. Herein, we review clinical studies reporting differences in oral microbial communities in inflammatory bowel diseases (IBDs), with a focus on Crohn's Disease (CD), as well as evidence from experimental models. While available studies support evidence for the direct transmission of oral-derived bacteria to gut, further work is needed to clarify whether such transmission results in stable colonization of intestinal niches and the establishment of a persistent host-microbe state that influences host physiology. To date, evidence from clinical and murine studies suggests three routes of the oral-gut axis, which in turn directly or indirectly exacerbate intestinal inflammation and contribute to IBD pathogenesis: (i) direct invasion of pathobionts through swallowing, (ii) migration of the oral pathogen activated pro-inflammatory immune cells, (iii) systemic inflammation triggered by oral pathogens such as Porphyromonas gingivalis. Although the role of oral microbiome in systemic diseases is becoming more apparent, sophisticated clinical and experimental studies are needed to elucidate the direct and indirect oral-gut communication mechanisms, including the contribution of oral microbial metabolites. Future directions may include evaluating the diagnostic and therapeutic potential of the oral microbiome and metabolome.
    Keywords:  Crohn’s disease; IBD; gut microbiome; oral microbiome; oral–gut axis
    DOI:  https://doi.org/10.3390/microorganisms14040810
  24. Front Immunol. 2026 ;17 1793621
    The oral-vascular axis: immune mechanisms linking periodontal dysbiosis to systemic vascular pathology.
    Jie Yu, Wen-Wen Zhuang, Bo Lei, Rong-Yan Shan, Xi-Meng Wang, Peng Qu, Matthias Hannig, Yong Liu.
      Periodontitis is among the most prevalent chronic inflammatory diseases worldwide and may affect vascular health beyond the oral cavity. Framed within the concept of an oral-vascular axis, this review synthesizes clinical and mechanistic evidence linking periodontal disease with atherosclerotic cardiovascular disease (ASCVD). Epidemiological studies and meta analyses consistently associate periodontitis with higher risks of coronary heart disease (CHD), stroke, and cardiovascular mortality, with modest but reproducible effect sizes that persist after adjustment for traditional risk factors. However, heterogeneous study designs and residual confounding preclude definitive causal inference. Interventional evidence is currently dominated by surrogate endpoints, and event-level cardiovascular benefit from periodontal therapy remains unproven. Mechanistically, chronic periodontal inflammation may influence endothelial function and atherogenesis through interlocking pathways that can be viewed as a spatiotemporal, dual-regulatory network of immunity and metabolism: local dysbiosis and barrier disruption increase systemic access to microbial ligands and vesicular cargo, while systemic immune activation interacts with metabolic remodeling to shape inflammatory set-points and vascular susceptibility. Microbe-derived and host-microbe co-metabolites may further modulate redox balance, inflammatory tone, and vascular homeostasis within this network. We highlight limitations of existing interventional trials, methodological challenges in microbiome- and genetics-based causal inference, and priorities for translational research. Clinically, the oral-vascular axis motivates interdisciplinary exchange and research-facing collaboration that integrates oral health assessment with immune and vascular phenotyping, while recognizing that cardiovascular benefit from periodontal interventions remains investigational and requires event-driven validation.
    Keywords:  atherosclerosis; endothelial dysfunction; periodontal dysbiosis; periodontitis; trained immunity; vascular inflammation
    DOI:  https://doi.org/10.3389/fimmu.2026.1793621
  25. Health Sci Rep. 2026 May;9 e72439
    Efficacy of a Salmonella Bacteriophage Cocktail Against Multidrug-Resistant Salmonella Isolates From Clinical and Food Samples.
    Taras Gabisonia, Manana Loladze, Maia Zarnadze, Natia Tamarashvili, Natela Chakhunashvili, Manana Nadiradze, Maia Alibegashvili, Tatiana Eliava, Tamar Kalandarishvili, Teimuraz Katamadze.
       Introduction: Salmonella is a significant foodborne pathogen responsible for severe gastroenteritis and systemic infections in humans and animals. The increasing prevalence of antimicrobial-resistant Salmonella strains poses a major public health challenge. This study aimed to investigate the antimicrobial resistance patterns of Salmonella isolates obtained from various sources, including food and human clinical samples, and to study the effectiveness of bacteriophages against isolated strains.
    Materials and Methods: A total of 80 S. Typhimurium isolates were obtained from two clinics between 2015 and 2022, and 16 ground meat samples were collected from agricultural markets. Standard microbiological methods were used for Salmonella isolation, including culture-based techniques and biochemical confirmation. The antimicrobial susceptibility of the isolates was determined using the disk diffusion method using 8 common antibiotics. New bacteriophages were isolated against multidrug-resistant Salmonella isolates. Electron microscopy for bacteriophage morphology investigation was employed.
    Results: Antimicrobial susceptibility testing revealed high resistance rates to tetracycline, streptomycin, ampicillin, chloramphenicol and ciprofloxacin, with multidrug resistance (MDR) observed in 16% of the isolates. The phage cocktail composed of six phages showed efficacy against 88.3% S. Typhimurium strains of different origins.
    Conclusion: The study highlights the widespread occurrence of antimicrobial-resistant Salmonella in food and human samples. The presence of MDR strains poses a serious threat to public health, necessitating biosecurity interventions to limit the spread of resistant Salmonella strains. The bacteriophages assessed in this study demonstrated significant potential for the biocontrol of Salmonella strains. The phage cocktail may be used for both food safety and therapeutic purposes, particularly against antibiotic-resistant bacteria causing salmonellosis.
    DOI:  https://doi.org/10.1002/hsr2.72439
  26. Biomedicines. 2026 Apr 18. pii: 926. [Epub ahead of print]14(4):
    The Wound Healing: A Mystery Still to Be Solved-What Is the Future?
    Montserrat Fernández-Guarino, María Luisa Hernández Bule, Stefano Bacci.
      This perspective contains the current understanding of the cellular and molecular mechanisms involved in wound healing (the articles taken into consideration relate to the three-year period 2023-2025). Nevertheless, these biological pathways remain inadequately characterized; this is seen by the modifications leading to pathological conditions, such as keloids, chronic wounds, or hypertrophic scars and diabetic wounds. Focus is also directed to novel therapy suggested for these types of conditions. Understanding these scientific issues is crucial for professionals across many fields who see such presentations often.
    Keywords:  acute wounds; cellular infiltrate; chronic wounds; keloids; scars
    DOI:  https://doi.org/10.3390/biomedicines14040926
  27. Clin Exp Dent Res. 2026 Jun;12(3): e70341
    The Silent Link: Exploring the Impact of Periodontal Diseases on Head and Neck Carcinogenesis.
    Yashmin Afshar, Nima Rezaei.
       OBJECTIVES: Oral dysbiosis can accelerate the progression of head and neck squamous cell carcinoma (HNSCC) by fostering a pro-inflammatory, immunosuppressive, and metabolically altered environment. This narrative review examines the relationships between periodontitis-associated bacteria and HNSCC, focusing on their impact on oncogenic pathways, immune modulation, and epigenetic alterations.
    MATERIALS AND METHODS: A comprehensive search of PubMed and Google Scholar was conducted up to January 28, 2026, without time limitations, using all relevant keywords related to HNSCC, head and neck cancers, periodontitis, and the oral microbiome.
    RESULTS: Key periodontitis-associated bacteria, including Fusobacterium nucleatum, Porphyromonas gingivalis, Capnocytophaga gingivalis, and Prevotella intermedia, may play a vital role in HNSCC. These bacteria stimulate several oncogenic pathways, including Wnt/β-catenin, NF-κB, and PI3K/Akt, enabling HNSCC to evade immune responses, trigger epithelial-to-mesenchymal transition and angiogenesis, and encourage cell proliferation and stemness. Furthermore, microbial interactions within the tumor microenvironment significantly impact treatment resistance, particularly in the context of immune checkpoint inhibitor therapy.
    CONCLUSIONS: Incorporating periodontal screening, microbiome profiling, and bacterial-targeted therapies into oncology could enhance treatment outcomes for HNSCC. Future research should investigate CRISPR-based microbial interventions, targeted epigenetic therapies, and microbiome-driven precision oncology strategies.
    Keywords:  head and neck cancer; oral microbiome; periodontitis
    DOI:  https://doi.org/10.1002/cre2.70341
  28. ISME J. 2026 May 08. pii: wrag113. [Epub ahead of print]
    Eco-evolutionary responses to plasmid-dependent phage constrain the spread of multidrug resistance plasmids.
    Daniel Cazares, Eliza Rayner, Adrian Cazares, Wendy Figueroa, David Goulding, Samuel T E Greenrod, Adam J Mulkern, Michelle Y Y Yin, Tao He, Nick Thomson, Michael A Brockhurst, R Craig MacLean.
      Phage therapy offers a promising alternative to antibiotics for treating multidrug-resistant infections. Plasmid-dependent phages (PDPs) are particularly attractive as therapeutics because they can both kill targeted pathogens and prevent the further spread of antibiotic resistance genes encoded by plasmids. However, the evolutionary trajectories of multidrug-resistance (MDR) plasmids under the selective pressure of PDPs remain poorly understood, particularly in eco-evolutionary contexts that remain permissive to plasmid conjugation. We experimentally evolved populations of Escherichia coli carrying the MDR plasmid RP4 in the presence of the plasmid-dependent phage PRD1 under conditions where the benefits of conjugation were either strong or weak. When opportunities for conjugation were rare, PRD1 only transiently suppressed the conjugative plasmid population due to the rapid evolution of phage-resistant plasmids lacking conjugative ability. Increasing ecological opportunities for conjugation enhanced plasmid suppression and delayed the evolution of phage-resistant plasmids. PRD1 resistance was associated with plasmid loss and reduced conjugative ability, although this trade-off was complex because resistance mutations had heterogeneous effects on pilus production and conjugation. Mutations and IS-mediated inactivation in conjugation genes generated a spectrum of resistance phenotypes, from partial resistance (trbB, trbL) to complete resistance (virB4/trbE). Bioinformatic analysis of publicly available IncP plasmids revealed frequent truncations of the VirB4/TrbE protein, suggesting that plasmid-dependent phages may represent an important selective pressure shaping plasmid evolution in natural populations. Our results demonstrate an evolutionary trade-off between conjugative ability and phage resistance that cannot be easily circumvented by plasmids. Targeting multidrug-resistance plasmids with PDPs is likely to drive loss of conjugation, limiting the transfer of antibiotic resistance genes in microbial communities.
    Keywords:  Plasmid-dependent phage; conjugation; conjugative pili; multidrug resistance; phage resistance; phage therapy; plasmid; plasmid evolution
    DOI:  https://doi.org/10.1093/ismejo/wrag113
  29. Sci Rep. 2026 May 08.
    A DPP inhibitor suppresses periodontitis via antibacterial effect targeting Porphyromonas gingivalis.
    Yukari Aoki-Nonaka, Yukako Minato, Koushi Hidaka, Yuko Warita, Daiki Ando, Hnin Yu Lwin, Aoi Matsugishi-Nasu, Naoki Takahashi, Akihiro Nakamura, Wataru Ogasawara, Mizuki Sekiya, Yasumitsu Sakamoto, Koichi Tabeta.
      Porphyromonas gingivalis is the most common periodontal pathogen. P. gingivalis dipeptidyl peptidase 7 (PgDPP7) belongs to a new class of serine peptidases, family S46. S46 peptidases are absent in mammals. Therefore, these enzymes are promising targets for novel antibacterial agents. In this study, inhibitors were designed based on the cocrystal structures of valyl-tyrosine and phenylalanyl-tyrosine, which bind to the active centers of DPP7 derived from bacteria, and dipeptide derivatives that inhibit PgDPP7 were obtained. The active compound KGDI-109, the first peptidyl inhibitor of S46 peptidases, exerted an inhibitory effect against P. gingivalis growth at a minimum inhibitory concentration of 1.56 µM. In C57BL/6 N male mice with induced periodontitis, the oral administration of KGDI-109 significantly suppressed alveolar bone resorption and reduced the amount of P. gingivalis in the oral cavity, indicating that the DPP inhibitor suppresses periodontal disease by its antibacterial activity. This dipeptide derivative did not inhibit the growth of other oral bacteria, and its antibacterial action was presumed to target bacteria possessing DPP, particularly P. gingivalis. Furthermore, KGDI-109 may be more effective than azithromycin in maintaining the gut microbial diversity and reducing adverse health effects. KGDI-109 can be a novel treatment for periodontal diseases targeting P. gingivalis.
    Keywords:   Porphyromonas gingivalis ; Alveolar bone loss; Antibacterial agents; Dipeptidyl peptidase; Periodontal disease; Periodontal medicine
    DOI:  https://doi.org/10.1038/s41598-026-52648-8
  30. Dent Mater. 2026 May 04. pii: S0109-5641(26)00287-3. [Epub ahead of print]
    Challenges and future directions in AI-driven biomaterials for microbiome-associated oral infectious diseases: A systematic review.
    Yu Cheng, Yanchun Wang, Tao Luo, Lvhua Guo.
      Oral biofilm-induced antimicrobial resistance is the core pathogenic mechanism of microbiome-associated oral infectious diseases (dental caries, periodontitis, peri-implantitis, and endodontic infection). Traditional therapies and biomaterials are limited by poor biofilm penetration, drug resistance induction, single functionality, and inadequate adaptation to dynamic oral microenvironmental changes (e.g., pH fluctuations, salivary rinsing, masticatory stimulation). Artificial intelligence (AI) has transformed the field by integrating materials science, microbiology, and stomatology data. Via machine learning, deep learning, and multi-physics simulation, AI optimizes biomaterial physicochemical properties, decodes microenvironmental signals, constructs precise sensing-response loops, and supports the full chain of material design, performance prediction, and action simulation, advancing treatment from empirical intervention to precision regulation. This systematic review retrieved literature from PubMed, Embase, and Web of Science (January 2016-January 2026) using keywords across three dimensions: AI, biomaterials, and oral microbiome. Following inclusion/exclusion criteria, 99 articles were included. It elaborates on five core mechanisms of AI-driven oral biomaterials (precise oral microbiome analysis, targeted material design/optimization, performance prediction/simulation, targeted delivery/intervention, effect evaluation/dynamic regulation), analyzes their applications in microbiome-targeted biomaterial research and development (R&D) and clinical practice for the four major oral infectious diseases, addresses technical bottlenecks (insufficient targeting specificity and precision of biomaterials, poor stability and durability in complex oral microenvironments, inadequate biofilm disruption capacity, and clinical translation obstacles), and proposes future directions (multimodal design to enhance targeting specificity, structural and component optimization to improve stability/durability, development of multi-mechanism synergistic biofilm disruption strategies, strengthening translational research for clinical application, and deep integration of AI in the full chain of biomaterial R&D). This work provides comprehensive theoretical and practical support for the R&D, optimization, and clinical translation of AI-driven microbiome-targeted oral biomaterials.
    Keywords:  Artificial intelligence; Microbiome-associated oral infectious diseases; Oral biomaterials; Oral microbiome
    DOI:  https://doi.org/10.1016/j.dental.2026.04.025
  31. Antonie Van Leeuwenhoek. 2026 May 06. pii: 119. [Epub ahead of print]119(6):
    Exploring the oral microbiome: from traditional techniques to advanced omics and databases.
    Pankaj Kumar Arora, Mushtaq Ali, Aditya Pratap Singh, Vimal Kumar Dubey, Alok Srivastava, Sanjay Kumar Garg.
      The oral microbiome comprises analysis of microbes within the oral cavity. Omics, molecular, and bioinformatic methods have significant functions in examining the diversity, composition, and function of the oral microbiome. Molecular techniques, especially 16S and 18S rRNA sequencing, have transformed the study of the oral microbiome. Analysis by 16S rRNA gene sequences of the oral sample creates a broad portrait of the species composition of the oral microbiome and both existing and new species of bacteria. It is instrumental in detecting bacterial pathogens at specific levels, specifically those involved with dental caries, periodontal disease, and oral malignancy. Paralleling the above, analysis by 18S rRNA gene sequencing elicits information related to the composition of fungal as well as protist members within the oral microbiome that plays significant roles for oral health. It can detect oral cavity parasitic infections, which may lead to oral health conditions. Omics tools are general terms for the use of high-throughput approaches to study on a large scale a variety of biological molecules. Applying these technologies to the oral microbiome allows researchers to determine the genetic, transcriptomic, proteomic, and metabolomic profiles of microbes in the oral cavity. These tools help to obtain an overall picture of the oral microbiome, such as its composition, function, and interactions. There are several databases offering useful information on the oral microbiome. These databases store curated information regarding microbial communities in the oral cavity, which aid researchers in the exploration of oral microbiome diversity, composition, and functional characteristics. Some of the examples include Human Oral Microbiome Database (HOMD) and Oral Microbiome Database (OMD). In minireview, we have provided an overview of a variety of molecular and omics tools and databases utilized in the exploration of the oral microbiome.
    Keywords:  Database; Genomics; Microbiome; Omics; Proteomics; Transcriptomics
    DOI:  https://doi.org/10.1007/s10482-026-02332-8
  32. Microorganisms. 2026 Mar 30. pii: 777. [Epub ahead of print]14(4):
    Isolation and Characterization of Two Bacteriophages Infecting Bacillus anthracis: Biological Properties and Genomic Analysis.
    Xinyu Qin, Zongti Shao, Binbin Yu, Rongji Cao, Haipeng Zhang, Liyuan Shi, Pan Liu, Shaogui Zi, Jiao Yang, Ying Long, Cong Liu, Siyu Yan, Xiaoxia Yang, Zhengling Zhu, Youhong Zhong, Peng Wang.
      Anthrax is a zoonotic infectious disease characterized by high lethality and transmissibility. Its spores are highly stable and can persist in the environment for long periods. Furthermore, the overuse or improper use of antibiotics may contribute to bacterial resistance, complicating anthrax treatment. Phages can efficiently target and lyse Bacillus anthracis (B. anthracis), significantly reducing pathogen contamination and transmission risks in soil, water, and other environmental media. Compared to traditional chemical disinfectants and antibiotics, phages enable precise pathogen elimination while minimizing ecological disruption. In this study, two phages infecting B. anthracis, vB_BanM-JC307 (JC307) and vB_BanS-YL5 (YL5), were isolated and characterized. Both phages belong to the class Caudoviricetes. Genome sequencing revealed that JC307 and YL5 have sequence lengths of 148,323 bp and 74,568 bp, respectively. Phylogenetic analysis indicates that JC307 is located in the same evolutionary branch as the Nachito phage of the Herelleviridae family, while YL5, although grouped with the Basilisk-like phages, forms an independent branch. As these two phages have been observed to exhibit lytic activity against all nine tested strains of B. anthracis, they could serve as auxiliary tools for pathogen diagnosis and assist in ecological management of anthrax-contaminated areas.
    Keywords:  Bacillus anthracis; Bacillus anthracis phage; Basilis-like phage; biological characteristics; genomic analysis
    DOI:  https://doi.org/10.3390/microorganisms14040777
  33. Biomed Mater. 2026 May 08.
    Bioactive wound dressings for diabetic foot ulcers: Mechanisms, materials, and clinical translation.
    Xue Wang, Nana Xiong, Huilin Hu, Jing Zhang, Kewei Hu, Yilin Chen, Lijia Cheng.
      Diabetic foot ulcers (DFU) represent a severe and challenging complication of diabetes, where healing is impaired by neuropathy, vascular dysfunction, persistent inflammation, and oxidative stress. Conventional therapies, including debridement and negative pressure wound therapy, often fail to fully restore the healing cascade, creating a need for advanced dressings that can actively interact with the wound microenvironment. This review systematically summarizes recent progress in DFU dressings, categorizing them into traditional, natural polymer-based (chitosan, alginate, collagen), synthetic polymer-based (PLGA, PVA, PEG), and multifunctional systems. A key focus is placed on elucidating their mechanisms of action, particularly in promoting angiogenesis, reducing oxidative stress, facilitating the transition of macrophages from proinflammatory M1 to reparative M2 phenotypes, and regulating critical signaling pathways such as AMPK, Wnt/β-catenin, and Nrf2/ARE. While preclinical evidence for many bioactive dressings is promising, their clinical translation remains limited, with only a few (e.g., collagen-based, silveralginate dressings) currently approved for use. Future research directions should prioritize the development of multifunctional and responsive dressings, underpinned by robust clinical validation through standardized evaluation and large-scale trials. This review provides a comprehensive and critical synthesis of current evidence, highlighting both mechanistic insights and the existing gaps between laboratory research and clinical application in DFU dressing technology.
    Keywords:  Angiogenesis; Biomaterials; Clinical translation; Diabetic foot ulcer; Inflammation; Wound dressings; Wound healing
    DOI:  https://doi.org/10.1088/1748-605X/ae6aec
  34. J Clin Med. 2026 Apr 21. pii: 3154. [Epub ahead of print]15(8):
    Periodontitis and Pancreatic Cancer Risk: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.
    Kareelend Andreina Segura Cueva, Andrea Bermúdez Velásquez, Carlos Andrés Guim Martínez, Luis Chauca-Bajaña, Leonardo Javier Siguencia Suárez, Byron Velásquez Ron, Carlos E Cuevas-Suárez, Abigailt Flores-Ledesma, Alejandro Ismael Lorenzo-Pouso, Andrea Ordoñez Balladares.
      Introduction: Pancreatic cancer is one of the most lethal malignancies worldwide, and its incidence continues to rise. Periodontitis, a highly prevalent chronic inflammatory disease, has been linked to several systemic conditions, including a potential increase in pancreatic cancer risk. However, the available epidemiological evidence remains heterogeneous and fragmented. Objective: To evaluate whether periodontitis is associated with an increased risk of pancreatic cancer through a systematic review and meta-analysis of observational studies. Materials and Methods: A comprehensive search was conducted in PubMed, EMBASE, Web of Science, Scopus, the Cochrane Library, ClinicalTrials.gov, and the WHO regional databases, following PRISMA guidelines. Cohort, case-control, and cross-sectional studies assessing periodontitis through clinical parameters, radiographic measures, or tooth loss-and reporting pancreatic cancer risk (HR, RR, or OR)-were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analyses, meta-regressions, leave-one-out sensitivity analyses, influence diagnostics, publication bias assessment, and Trial Sequential Analysis (TSA) were performed. Results: Eight observational studies (primarily cohort designs) (n = 476,245 participants) met the inclusion criteria. Periodontitis was associated with an increased risk of pancreatic cancer (pooled HR = 1.56; 95% CI: 1.28-1.89), with moderate heterogeneity (I2 = 55.5%). Sensitivity and influence analyses confirmed the robustness of the estimate. TSA showed a consistent trend, although the cumulative evidence remains insufficient for a definitive conclusion. Conclusions: Observational evidence suggests a modest statistical association between periodontitis and pancreatic cancer risk. However, the absolute risk increase is very small, and Trial Sequential Analysis indicates that cumulative evidence remains insufficient to establish causality or to support preventive or clinical recommendations. Further large-scale prospective studies with standardized periodontal assessments are required.
    Keywords:  inflammation; pancreatic neoplasms; periodontitis; risk factors; tooth loss
    DOI:  https://doi.org/10.3390/jcm15083154
  35. Microbiol Spectr. 2026 May 04. e0356525
    ICP1 bacteriophage treatment antagonizes colonization of the zebrafish larval intestine by Vibrio cholerae.
    Adam Sidi Mabrouk, Jamie S Depelteau, Chiara Foini, Annabel Kempff, Sebastiaan Jonker, Susanne Brenzinger, Ronald Limpens, Manuel Majrouh, Annemarie H Meijer, Ariane Briegel.
      Outbreaks of cholera pose a major threat to human health. Currently, antibiotics are the most effective treatment against the causative agent, the bacterium Vibrio cholerae. However, the use of antibiotics eventually leads to the emergence of resistant strains, which necessitates the need for alternative approaches. The use of bacteriophages to target the infection by antibiotic-resistant bacteria is one promising alternative. While clearance of Vibrio cholerae with the use of phages has been performed on several animal models, none of these models are naturalistic hosts of V. cholerae. Therefore, we set out to investigate the interaction between V. cholerae and bacteriophage ICP1 both in vitro and in vivo in a naturalistic host, the zebrafish model, Danio rerio. To study the interplay between host, bacteria, and phages, we used a combination of light and ultrastructural imaging techniques, including confocal fluorescence microscopy, serial block face scanning electron microscopy (EM) imaging, and cryogenic EM, which allowed us to investigate both the colonization process by V. cholerae and clearance by the ICP1 bacteriophage. In addition, we determined the effects of the microbiome on this treatment by using germ-free, conventionalized, and monoassociated zebrafish larvae as a host. Independent of the presence and composition of microbiomes used here, V. cholerae efficiently colonized the larval intestine. Finally, we demonstrate significant in vivo clearance of V. cholerae N16961-dsRED by ICP1, underscoring the role of phage-bacteria dynamics in shaping pathogen colonization within the zebrafish larval host.
    IMPORTANCE: Cholera remains a life-threatening disease that causes recurring outbreaks and significant mortality, particularly in developing and conflict-affected regions. As antimicrobial resistance continues to rise, there is an urgent need to better understand the ecological and microbial dynamics that govern Vibrio cholerae colonization and persistence. This research investigates how V. cholerae interacts with bacteriophages, the host environment, and the resident microbiota within a natural vertebrate host, offering new insights into the factors that influence pathogen clearance and shaping of the gut ecosystem during infection. The powerful combination of serial block-face scanning and cryogenic electron microscopy, fluorescence microscopy, and traditional colony/plaque counting methods revealed previously unobserved aspects of the interplay between host, pathogen, phages, and selected microsymbionts, highlighting phage-driven clearance of V. cholerae during colonization.
    Keywords:  Vibrio cholerae; bacteriophage therapy; confocal microscopy; cryo-EM; intestinal microbiome
    DOI:  https://doi.org/10.1128/spectrum.03565-25
  36. Can J Diabetes. 2026 May 02. pii: S1499-2671(26)00074-2. [Epub ahead of print]
    Canadian Patient Perspectives on Facilitators and Barriers to Diabetic Foot Ulcer Care: A Scoping Review.
    Shireen Fikree, Rudra Pandya, Virginie Blanchette, Tom Weisz, Alla Iansavitchene, Charles de Mestral.
       OBJECTIVE: To review Canadian patient and caregiver perspectives on the facilitators and barriers to diabetic foot ulcer (DFU) care.
    METHODS: We conducted a scoping review in collaboration with a patient partner, following the Preferred Reporting Items for Systematic Reviews guidelines (PRISMA-ScR). Grey literature and primary studies from Medline, CINAHL and EMBASE were searched from inception to February 2024. Studies of adults with active or healed DFUs and their caregivers were included. Data were independently screened and extracted by two reviewers and key themes were synthesized collaboratively.
    RESULTS: Twenty-two studies representing 400 patients or caregivers were included, with most individuals living in Ontario (n=15 articles, 68.1%). Five overarching themes capturing facilitators and barriers to DFU care were identified: Prevention, Access to Care, Patient Education, Wound Care, and Patient Impact. Reported barriers included emotional distress, limited mobility, low awareness of self-management strategies, and delayed referrals, while key facilitators involved caregiver and community support as well as education from healthcare providers.
    CONCLUSIONS: Canadian diabetic foot screening and DFU treatment (preservation) programs should focus on improving access, empowering patients through education, and leveraging community support partners to promote self-management and amputation prevention.
    Keywords:  Diabetic foot; amputation prevention; foot screening; foot ulcer; limb preservation; patient participation
    DOI:  https://doi.org/10.1016/j.jcjd.2026.04.009
  37. Structure. 2026 May 04. pii: S0969-2126(26)00111-5. [Epub ahead of print]
    Cryo-EM structures of prevalent gut phage PD491P1 uncover extensive disulfide stabilization and distinct structural adaptations.
    Can Cai, Aohan Wang, Qianqian Shao, Jieqiong Zhang, Yueting Wang, Hongli Hu, Ke Yuan, Lin Li, Xiaofang Wang, Qianglin Fang, Yingfei Ma.
      Bacteriophages play crucial roles in modulating the human gut microbiome, yet structural characterization of prevalent gut phages remains limited. Here, we present high-resolution cryo-EM structures of Parabacteroides phage PD491P1, which is one of the most abundant bacteriophages in the human gut. The structures reveal its mature virion organization, including the capsid, head-to-tail interface, and tail tip regions. Strikingly, PD491P1 exhibits an exceptionally extensive disulfide bond network that covalently stabilizes nearly the entire virion. Unique structural features include an elaborate portal-adaptor-terminator interface and distinctive, upward-pointing and flexible tail fibers with multiple putative host recognition domains. These structural adaptations may enable phage PD491P1 to achieve survival and robust infection in the challenging gut environment. These findings expand our understanding of gut phage structural diversity, reveal mechanistic insights into phage stability and infection, and provide a foundation for future development of phage-based microbiome therapeutics.
    Keywords:  Parabacteroides phage PD491P1; cryo-EM; disulfide bond network; gut microbiome; host recognition; virus assembly
    DOI:  https://doi.org/10.1016/j.str.2026.04.005
  38. Appl Environ Microbiol. 2026 May 04. e0230325
    Engineering a T7 bacteriophage to attenuate LPS-driven inflammatory responses during bacteriolysis.
    Tong Yu, Junjiao Pang, Mengge Chen, Qi Sun, Jiaqi Pu, Deshu Wang, Qingling Liu, Fengtang Yang, Hongkuan Deng.
      Bacterial lysis during treatment of Gram-negative infections can release lipopolysaccharide (LPS) and aggravate inflammation. Here, we engineered two complementary T7 bacteriophages: T7-nluc, a NanoLuc reporter bacteriophage for real-time monitoring of viable bacteria, and T7-phoa, a therapeutic bacteriophage that releases alkaline phosphatase (PhoA) during lysis to reduce LPS bioactivity. Both engineered bacteriophages retained lytic activity similar to that of wild-type T7. In vitro, T7-nluc produced a low-background bioluminescent signal that reflected bacterial burden, whereas T7-phoa released catalytically active PhoA into the extracellular environment. In Galleria mellonella and Danio rerio infection models, T7-nluc enabled dynamic monitoring of infection progression, while T7-phoa improved survival, reduced inflammatory responses, and accelerated inflammatory resolution without compromising bacterial clearance. These findings support a modular bacteriophage engineering strategy that combines bacterial killing, real-time infection monitoring, and local attenuation of LPS-driven inflammation, offering a potential approach for improving bacteriophage-based treatment of Gram-negative infections.
    IMPORTANCE: Bacteriophage therapy is being reconsidered for treating drug-resistant Gram-negative infections, but there is concern that rapid bacterial lysis may release LPS and worsen inflammation. We used bacteriophage T7 as a platform to test whether bacteriophages can be engineered to both fight bacteria and soften these harmful host responses. First, we created a NanoLuc reporter bacteriophage that produces light only when it grows in live bacteria, confirming that engineered bacteriophages can deliver active proteins directly in infected animals. We then built a therapeutic T7-phoa bacteriophage designed to release enzymatically active alkaline phosphatase upon on-target lysis, thereby providing lysis-coupled local phosphatase activity at the infection site. In both G. mellonella and Danio rerio models, infection-site fluids collected after treatment showed elevated phosphatase activity in the T7-phoa group, and the treatment was associated with lower inflammatory peaks, improved survival, and preserved bacterial clearance. Together, these results support a modular route for bacteriophage-based strategies that couple bacterial killing with real-time reporting and local control of LPS associated inflammation.
    Keywords:  alkaline phosphatase; bacteriophage therapy; engineered bacteriophage; inflammatory factor
    DOI:  https://doi.org/10.1128/aem.02303-25
  39. J Clin Med. 2026 Apr 15. pii: 2994. [Epub ahead of print]15(8):
    Clinical Profile, Risk Factors, and Microbial Dysbiosis in Periodontitis: Findings from an Adult Cohort and Microbiome-Based Predictive Models.
    Sofia Jimenez de Nunzio, Jesus Pilo, Marta Bruna Del Cojo, Caridad Margarita Arias-Macias, Barbara Manso de Gustin, Filipa Nunes, Eva Lago Pacheco, Clara Esteban Escobar, Francisco Tercero-Mora, Sergio Portal-Nuñez, Ana Adell Perez, Manuel Macias Gonzalez.
      Background/Objective: Periodontitis is a chronic inflammatory disease influenced by clinical, behavioral, and microbial determinants. However, the contribution of these factors to disease remains a topic of debate, particularly in untreated adult populations. This study aims to characterize the clinical, epidemiological, and microbial features associated with periodontitis in an adult cohort and to compare the discriminatory performance of microbiome-based predictive models with conventional clinical-behavioral models. Methods: A cross-sectional study was conducted in 943 adults. Periodontal status was determined by experienced clinicians according to the 2017 World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions. Clinical variables, behavioral factors (smoking, bruxism, diet), intraoral conditions (caries and malocclusion), and systemic comorbidities were recorded. The oral microbiome was analyzed using targeted PCR for selected periodontal bacteria. Predictive models were constructed using logistic regression and least absolute shrinkage and selection operator (LASSO) variable selection. Results: Periodontitis was diagnosed in 47.2% of participants. Age, smoking, and bruxism were significantly associated with periodontitis. Malocclusion was the only significant intraoral predictor (OR = 2.00). Individuals with periodontitis exhibited increased levels of periodontopathogens, including P. gingivalis, T. forsythia, and E. corrodens, along with reduced levels of S. mutans. Microbiome-based models demonstrated superior discriminatory performance (AUC = 0.76, LASSO). E. corrodens and C. sputigena were independently associated with greater probing depth (p < 0.001). Conclusions: Microbiome-based predictive models, particularly at the species level, showed better discriminatory performance than conventional clinical-behavioral models. These findings support the potential utility of salivary microbial signatures as adjunctive, non-invasive biomarkers of periodontal inflammatory status.
    Keywords:  biomarkers; dysbiosis; malocclusion; oral microbiome; periodontitis; predictive model
    DOI:  https://doi.org/10.3390/jcm15082994
  40. Microorganisms. 2026 Mar 26. pii: 736. [Epub ahead of print]14(4):
    Periodontitis and Chronic Liver Disease: Mechanistic Insights Focusing on Porphyromonas gingivalis-A Narrative Review.
    Yue Ying, Yuwei Nie, Jiahui Zhao, Qin Dong, Meixian Chen, Aijia Jiang, Nan Liu, Tong Xu, Junchao Liu, Yaping Pan, Li Lin, Dongmei Zhang.
      Porphyromonas gingivalis (P. gingivalis), a keystone pathogen in periodontitis, has been increasingly implicated in compromising hepatic health and exacerbating the pathogenesis of liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), chronic hepatitis, and cirrhosis. Current studies have identified three well-established pathways through which periodontitis contributes to chronic liver disease progression: systemic inflammatory responses, liver cells dysfunction, and gut microbiota dysbiosis. This review systematically elucidates the associations between periodontitis and chronic liver disorders, consolidates evidence on the canonical molecular mechanisms involved, and further proposes potential yet understudied pathways such as ferroptosis, immune evasion, and endothelial-mesenchymal transition (EndMT). By integrating these insights, this work aims to provide novel perspectives for mitigating the systemic adverse effects of periodontitis while offering a theoretical foundation for future research and clinical therapeutic strategies.
    Keywords:  Porphyromonas gingivalis; chronic liver diseases; endothelial–mesenchymal transition; ferroptosis; immune evasion; periodontitis
    DOI:  https://doi.org/10.3390/microorganisms14040736
  41. Vet Microbiol. 2026 Apr 24. pii: S0378-1135(26)00178-1. [Epub ahead of print]318 111046
    Isolation and characterization of a therapeutic lytic phage cocktail against mastitis-associated Enterococcus faecalis with antibiofilm activity and in vivo efficacy.
    Mücella Bayirli Nacaroglu, Abdulkerim Karaynir, Rümeysa Gülsu Özkan, Melis Yalcin, Süheyla Türkyılmaz, Özkan Aslantaş.
       BACKGROUND: Antimicrobial-resistant (AMR) mastitis-associated Enterococcus faecalis and Enterococcus faecium threaten dairy production, animal welfare, and public health due to economic losses and zoonotic risk. Environmental mastitis is increasingly linked to E. faecalis, which is frequently detected in milk and animal-derived products.
    METHODS: Three novel lytic bacteriophages-vB_Ef3_HMKU_24 (vB_Ef3), vB_Ef5_HMKU_24 (vB_Ef5), and vB_Ef32_HMKU_24 (vB_Ef32)-were isolated from wastewater in Türkiye and characterized for host range, stability, replication kinetics, antibiofilm activity, in vivo efficacy (Galleria mellonella), and genomic features.
    RESULTS: The phages vB_Ef3, vB_Ef5, and vB_Ef32 exhibited strong and specific lytic activity against E. faecalis (up to 69.1% individually; 72.7% as a cocktail) with no activity against other species. They remained active across pH 4-10 and up to 70 °C. Optimal MOIs were 10 (vB_Ef3), 0.1 (vB_Ef5), and 0.001 (vB_Ef32). vB_Ef5 and vB_Ef32 fully suppressed bacterial growth for 24 h, whereas vB_Ef3 caused transient inhibition. Burst sizes were ∼2019, ∼153, and ∼287 PFU/cell for vB_Ef3, vB_Ef5, and vB_Ef32, respectively. All phages significantly inhibited and eradicated biofilms; vB_Ef5 was the most effective single agent (71% inhibition, 68% eradication), while the cocktail achieved the highest activity (82% and 73%). In the G. mellonella infection model, phage treatment improved larval survival, with the cocktail reaching ∼90% and showing no toxicity. Genomic analyses (40.3-58.6 kb; 34.9-39.5% GC; 78-118 ORFs) confirmed strictly lytic phages encoding endolysins and lacking virulence or AMR genes, classified within the Herelleviridae.
    CONCLUSION: Collectively, these findings demonstrate that the combined use of vB_Ef3, vB_Ef5, and vB_Ef32 represents a safe, stable, and highly effective phage cocktail with strong potential as a precision therapeutic strategy against multidrug-resistant E. faecalis-associated bovine mastitis.
    Keywords:  Antibiofilm activity; Antimicrobial resistance; Bovine mastitis; Enterococcus faecalis; Galleria mellonella; Phage-therapy
    DOI:  https://doi.org/10.1016/j.vetmic.2026.111046
  42. Curr Opin Virol. 2026 May 05. pii: S1879-6257(26)00036-2. [Epub ahead of print]76 101544
    Immunopathogenic insights into members of the class Bunyaviricetes: a comparative review of emerging zoonotic threats.
    Mark Anthony B Casel, Nam-Hyuk Cho, Jae U Jung, Young Ki Choi.
      The class Bunyaviricetes encompasses a diverse group of vector- and rodent-borne viruses, many of which are major human pathogens causing severe and often lethal diseases worldwide. These include Lassa fever virus (Arenaviridae), hantaviruses such as Hantaan and Andes viruses (Hantaviridae), Crimean-Congo hemorrhagic fever virus (Nairoviridae), La Crosse and Oropouche viruses (Peribunyaviridae), and Rift Valley fever, severe fever with thrombocytopenia syndrome, and Toscana viruses (Phenuiviridae). Clinical syndromes range from hemorrhagic fever with multiorgan failure, vascular leak, and shock to acute encephalitis and severe respiratory distress. Despite their public health impact, safe and effective vaccines or targeted therapeutics are lacking for most bunyaviricetes diseases, leaving supportive care as the primary intervention. This review provides a comparative analysis of the immunopathogenesis of major human-pathogenic bunyaviricetes, highlighting shared and virus-specific strategies for innate immune evasion, cytokine modulation, and host cell targeting. Severe disease often arises from viral interference with key sensing pathways, such as RIG-I/MDA5 and downstream IRF and NF-κB signaling, which either suppresses interferon responses or leads to dysregulated inflammation. By integrating molecular, immunological, and clinical insights, we outline how these immune-virus interactions shape disease trajectory and severity. Understanding these mechanisms is critical for guiding the rational design of vaccines, antivirals, and immunomodulatory therapies, and for strengthening preparedness against these persistent zoonotic threats.
    DOI:  https://doi.org/10.1016/j.coviro.2026.101544
  43. Annu Rev Virol. 2026 May 06.
    Discovering New Jumbo Phage Biology with Cryo-Electron Microscopy.
    Niklas Klusch, Elizabeth Villa.
      Phages invade and replicate in bacteria, resulting in host cell death. In our review, we highlight the impact of electron microscopy on phage research. Recent advances in the field of cryo-electron microscopy, including single-particle analysis, focused ion beam milling, and cryo-electron tomography, play a crucial role in understanding the structure and mechanisms involved in phage replication. Here we focus on jumbo phages, characterized by a large ∼200-kb genome, many of which belong to the new Chimalliviridae family whose genome encodes for a unique replication cycle. Upon phage genome injection into the host cell, the DNA is surrounded by an early phage injection (EPI) vesicle that serves as a hub for initial synthesis of early phage proteins. One of these early proteins, chimallin, forms a nucleus that replaces the EPI vesicle and continues to protect the replicating phage DNA against the host defense systems.
    DOI:  https://doi.org/10.1146/annurev-virology-092623-102451
  44. Nutrients. 2026 Apr 16. pii: 1256. [Epub ahead of print]18(8):
    Age-Related Differences in Oral Microbiota Among Obese Patients with Periodontitis: A Systematic Review.
    Felicia Gabriela Beresescu, Razvan Marius Ion, Adriana Monea, Alina Ormenisan, Despina Luciana Bereczki-Temistocle, Liana Beresescu, Andrea Bors.
      Background: Obesity and periodontitis are linked through inflammatory and metabolic pathways, and the oral microbiota may mediate this interaction. Age-related changes in immunity, salivary function, and cumulative exposure may modify obesity-associated periodontal dysbiosis. Objective: We sought to synthesize the potential for age-related differences in the oral microbiota of adult obese patients with periodontitis and assess the strength of current literature in supporting age-specific interpretations. Methods: A systematic search of PubMed/MEDLINE, Scopus, and Embase identified 1088 records. After screening and full-text assessment, 50 studies that met the criteria for focused qualitative synthesis remained. Within that review corpus, 10 representative adult human studies provided the most direct evidence linking obesity or overweight, periodontal phenotype, oral microbiota, and age-relevant interpretation. Risk of bias was appraised with the Newcastle-Ottawa Scale. Results: Direct head-to-head microbiome comparisons between younger and older obese adults with periodontitis are rare. Direct evidence links obesity to greater periodontal inflammatory burden, enrichment of classical periopathogens and bridging taxa, and shifts in community structure. Contextual aging studies have suggested that older adults may more often harbor lower-diversity, persistence-oriented communities enriched in stress-tolerant, proteolytic, or opportunistic taxa, whereas younger obese adults more often show inflammation-amplifying consortia enriched in classical periopathogens and bridging taxa. However, these patterns remain largely hypothesis-generating because the evidence base is heterogeneous and predominantly cross-sectional. Conclusions: Age likely modifies the obesity-periodontitis-microbiota axis, but direct comparative evidence on adults remains limited. The current literature supports cautious age-aware interpretation within a systematic review framework rather than definitive age-specific microbial signatures or treatment algorithms.
    Keywords:  aging; dysbiosis; obesity; oral microbiota; periodontitis; systemic inflammation
    DOI:  https://doi.org/10.3390/nu18081256
  45. Bioengineering (Basel). 2026 Apr 08. pii: 436. [Epub ahead of print]13(4):
    Local Antibiotic-Loadable Carriers for the Treatment of Chronic Osteomyelitis: A Narrative Review.
    Andrea Sambri, Alessandro Bruschi, Cristina Scollo, Massimiliano De Paolis.
      Local antibiotic delivery has gained a central role as an adjunct to radical debridement in chronic osteomyelitis, allowing high antimicrobial concentrations at the infection site while reducing systemic toxicity. This narrative review summarizes the current clinical evidence on commercially available antibiotic-loadable bone substitutes, with particular focus on calcium sulfate (CaSO4)-based systems and biphasic calcium sulfate/hydroxyapatite (CaS/HA) composites. Nineteen studies were included. Differences in formulation, resorption kinetics, antibiotic elution profile and osteoconductive behavior are discussed, alongside clinical outcomes including recurrence of infection, reoperation rates and complication patterns. Finally, based on the currently available evidence and expert recommendations, practical guidance is proposed to support carrier selection in different clinical scenarios (cavitary vs. corticomedullary defects; high-risk soft tissue; polymicrobial or resistant infections). Across published series, although heterogeneous, infection eradication rates are generally high when local carriers are integrated into structured surgical protocols. Calcium sulfate carriers provide rapid resorption and robust early antibiotic release but are associated with higher rates of sterile wound drainage. In contrast, CaS/HA biocomposites demonstrate more gradual remodeling and radiographic integration, potentially improving defect consolidation and reducing wound-related morbidity, although leakage and cost considerations remain relevant.
    Keywords:  biodegradable carriers; bone substitute; calcium sulfate; chronic osteomyelitis; hydroxyapatite; local antibiotics
    DOI:  https://doi.org/10.3390/bioengineering13040436
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