bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–12–28
thirty-two papers selected by
Luca Bolliger, lxBio



  1. Front Cell Infect Microbiol. 2025 ;15 1751637
      
    Keywords:  antimicrobial resistance; artificial intelligence; bacteriophage research; endolysin; phage therapy
    DOI:  https://doi.org/10.3389/fcimb.2025.1751637
  2. NPJ Biofilms Microbiomes. 2025 Dec 25.
      The rise of multidrug-resistant bacteria, particularly biofilm-forming pathogens such as Staphylococcus epidermidis, highlights the urgent need for alternative antimicrobial strategies. Phage therapy, which uses phages to selectively infect and lyse bacterial cells, offers a promising solution. In this study, we evolved the lytic phage vB_Sep_Steph1 under both biofilm and planktonic conditions, using varying initial phage inoculum titers. Whole-genome sequencing of evolved populations revealed recurrent condition-dependent mutations in holins and structural genes with putative depolymerase activity-critical for host recognition and biofilm degradation. Phenotypic improvements in traits such as antibacterial efficacy and replicative fitness were observed to be highly dependent on both the presence of biofilm and the initial phage titer during evolution. Furthermore, some evolved phage lineages could delay bacterial resistance better than the ancestral strain. These findings support the utility of directed phage evolution to improve therapeutic efficacy and robustness, particularly against biofilm-associated infections.
    DOI:  https://doi.org/10.1038/s41522-025-00893-6
  3. Curr Opin Microbiol. 2025 Dec 18. pii: S1369-5274(25)00120-1. [Epub ahead of print]89 102698
      The increasing emergence of multidrug-resistant bacterial infections poses a major threat to humankind, with 10 million deaths predicted in 2050 as a result. Phage therapy has therefore regained attention as a promising approach to combat these pathogens. However, the ongoing evolutionary arms race between phages and bacteria has driven the accumulation of phage defense systems in bacterial populations, which can compromise the efficacy and generalizability of phage applications. Recently, nucleus-forming phages have been discovered and classified under the newly established phage family 'Chimalliviridae'. Chimalliviruses orchestrate a highly organized, nucleus-based replication that physically segregates phage DNA from host defenses, thereby enhancing replication efficiency and conferring resistance to a wide array of host defenses. Their unique replication strategy and subcellular organization far exceed that of classical phages, positioning them as candidates for a new class of 'next-generation phages' with superior therapeutic potential and biocontrol capabilities. This review will cover the current landscape of chimallivirus discovery, highlighting their association with bacterial pathogens, unique replication machinery, and interaction with bacterial defenses. Furthermore, it provides insights into chimallivirus-based therapeutic applications.
    DOI:  https://doi.org/10.1016/j.mib.2025.102698
  4. J Cyst Fibros. 2025 Dec 23. pii: S1569-1993(25)02545-7. [Epub ahead of print]
      Nontuberculous mycobacteria (NTM) cause pulmonary disease in people with cystic fibrosis (pwCF). Recommended prolonged antibiotic therapy has significant toxicity. Non-antibiotic therapies for NTM pulmonary disease and supporting evidence were identified. Online databases and trials registries were searched for randomised or non-randomised studies (NRSIs). Primary outcomes were microbiology, quality of life (QoL), adverse events, lung function and pulmonary exacerbations. Bias was assessed using the relevant Joanna Briggs Institute tool. Seven NRSIs assessed: phage therapy, CF transmembrane conductance regulator (CFTR) modulator therapy (ETI: elexacaftor/tezacaftor/ivacaftor), inhaled nitric oxide (INO) and surgical lung resection. All had varying response definitions and very low-certainty evidence. The phage therapy study reported NTM culture conversion (n=4), partial conversion (n=4), inconclusive response (n=4) or no response (n=4). In one study of ETI with antibiotics (n=7) or without (n=8), nine participants eradicated NTM after a year, with positive cultures decreasing during treatment compared to pre-treatment. In another study (n=91) NTM infection fell by approximately 75% after at least two months of ETI (no information on concomitant treatment). In three INO studies (n=16), NTM was eradicated (n=2), showed transient negative cultures (n=6) and reductions in bacterial burden (n=11). Comparing lung resection (n=3) to antibiotic therapy (n=6), all surgical patients cleared M abscessus remaining negative at 24 months; 4 patients taking antibiotics cleared NTM. All M avium complex (MAC)-positive patients (surgery, n=1; antibiotic, n=2) cleared infection. Currently, non-antibiotic therapies are considered case by case. Randomised studies are needed to increase evidence quality and inform clinical practice for interventions appearing safe and feasible in pilot studies.
    Keywords:  Cystic fibrosis; Nontuberculous mycobacteria; Systematic review
    DOI:  https://doi.org/10.1016/j.jcf.2025.12.014
  5. iScience. 2025 Dec 19. 28(12): 114107
      Capsule loss is a major mechanism by which bacteria evade phage infection. This has traditionally been attributed to mutations in capsule biosynthesis genes. Here, we investigated phage resistance in Klebsiella pneumoniae, a medically relevant encapsulated bacterium. Phage infection rapidly selected for resistant acapsular cells. As expected, transcriptomic analysis revealed a marked downregulation of capsule biosynthesis genes. However, full genome sequencing showed that capsule loss occurred without evidence of mutations, and acapsular phage-resistant cells were able to rapidly restore their capsule once phage pressure was removed. These findings highlight that phage-driven selective pressure can act on non-heritable variation in gene expression, providing a faster and more flexible resistance mechanism compared to the traditional mutation-selection process. This reversible resistance may complicate predictability and limit the long-term efficacy of phage therapy.
    Keywords:  Cell biology; Microbiology; Molecular biology
    DOI:  https://doi.org/10.1016/j.isci.2025.114107
  6. JHEP Rep. 2026 Jan;8(1): 101622
    MICROB-PREDICT
       Background & Aims: As portal hypertension progresses in cirrhosis, bacterial translocation across a compromised gut barrier leads to endotoxemia, systemic inflammation and immune dysfunction. Gut phages play a key role in these processes by influencing bacteria-host interactions. This study explores the role of the human gut virome in acute decompensation of cirrhosis and acute-on-chronic liver failure (ACLF).
    Methods: The fecal virome was longitudinally assessed by metagenomic sequencing in two independent cohorts: 93 patients (292 samples) with acute decompensation or ACLF from the PREDICT study, and 94 patients (94 samples) with decompensated cirrhosis undergoing TIPS (transjugular intrahepatic portosystemic shunt) surgery collected in a tertiary care setting. Besides descriptive analysis, phages were grouped according to their predicted bacterial host and lifestyle, and associated with clinical parameters.
    Results: Phage alpha-diversity was higher in patients with ACLF and correlated with ACLF severity. In the absence of ACLF, the phageome was dominated by virulent phages, but in ACLF, temperate phages became more prevalent. Genus-level analysis showed that phageomes were highly patient-specific. Lactococcus A phages were the only phage-host group predicting ACLF development (odds ratio [OR] = 14; Fisher test p = 0.0129). Enterococcus B phages (OR = 14.7; p = 0.0015; adj. p = 0.037) and their bacterial hosts (OR = 2.8; p = 0.020) were significantly more prevalent in cases of proven systemic bacterial infection. The presence of both phage families was linked to increased 90-day mortality rates.
    Conclusion: ACLF is characterized by increased fecal virome diversity and a shift from virulent toward temperate phages at disease onset. Our study links Lactococcus A phages to ACLF development, and Enterococcus B phages to bacterial infection, while both are associated with increased 90-day mortality.
    Clinical trial number: NCT03056612.
    Impact and implications: The human gut virome is a poorly investigated part of the human gut microbiome, especially in the context of decompensated cirrhosis and acute-on-chronic liver failure. This study identified two phage groups (Lactococcus A phages and Enterococcus B phages) with particular prognostic value. In the future, virome analysis of fecal samples could be useful for patient stratification in clinical practice.
    Keywords:  acute-on-chronic liver failure; acutely decompensated cirrhosis; fecal microbiome; fecal virome; gut phages; phage host prediction
    DOI:  https://doi.org/10.1016/j.jhepr.2025.101622
  7. Biosensors (Basel). 2025 Dec 01. pii: 785. [Epub ahead of print]15(12):
      Chronic wounds constitute a major global public health challenge, characterized by a high risk of infection, prolonged healing times, and frequent recurrence. Conventional wound assessment methods, which primarily rely on visual clinical inspection and laboratory-based analyses, are limited by inherent subjectivity, delayed feedback, and a lack of capacity for real-time monitoring of the dynamic biochemical changes at the wound site. Significantly, recent advancements in flexible electronics, nanomaterials, and energy harvesting technologies have boosted the rapid development of wearable electrochemical biosensors. These devices have emerged as a transformative platform for the continuous, non-invasive analysis of critical biomarkers within the wound microenvironment, including pH, temperature, inflammatory cytokines, metabolites, and pathogen-derived molecules. This review critically examines the latest progress in wearable electrochemical biosensors for wound monitoring and management. Key discussions include (1) the special requirements for sensor design, targeting the chronic wound's pathological characteristics; (2) cutting-edge development in self-powered systems, multimodal sensor integration, closed-loop theranostics, and artificial intelligence (AI)-assisted decision-making; and (3) a critical appraisal of challenges in accuracy, stability, biocompatibility, energy management, and clinical translation. Finally, the review explores future trends, such as biodegradable sensors, multi-parameter fusion algorithms, and remote intelligent management systems, with the aim of establishing a foundational framework and providing technical guidance for developing next-generation intelligent wound care solutions.
    Keywords:  chronic wound monitoring; closed-loop theranostics; infection diagnosis; intelligent wound management; real-time sensing; wearable electrochemical biosensor
    DOI:  https://doi.org/10.3390/bios15120785
  8. Environ Microbiol Rep. 2025 Dec;17(6): e70267
      Antibiotics revolutionized medicine in the 20th century by drastically reducing mortality from bacterial infections. However, their effectiveness is threatened by the global rise of antimicrobial resistance (AMR), driven by misuse, overuse, and environmental dissemination. This review explores the historical trajectory of antibiotics, the mechanisms of bacterial resistance, and the urgent need for innovation amid a declining antibiotic development pipeline. Herein, we highlight the scientific and economic barriers that have discouraged investment by major pharmaceutical companies and examine emerging strategies to address this crisis. Key advances in microbial bioprospecting, including cultivation improvement techniques and genome mining, are discussed alongside the role of high-throughput sequencing and bioinformatics in unlocking the metabolic potential of uncultivated microorganisms. Particular emphasis is placed on the integration of artificial intelligence and machine learning to accelerate drug discovery, predict antimicrobial activity, and identify resistance genes. Additionally, we present alternative therapeutic strategies beyond traditional antibiotics, such as phage therapy, antimicrobial peptides, quorum sensing inhibitors, synthetic conjugates, and vaccine development. Together, these interdisciplinary approaches offer promising pathways to revitalize the antimicrobial pipeline and address the growing threat of antibiotic resistance.
    Keywords:  antimicrobial resistance; bioactive compounds; novel antibiotic development; therapeutic strategies
    DOI:  https://doi.org/10.1111/1758-2229.70267
  9. Future Microbiol. 2025 Dec 25. 1-15
      The oral microbiome plays a major role in health, while its dysbiosis can contribute to oral and systemic disorders. The oral cavity hosts a complex community of commensal and pathogenic microbes, and disruptions in this balance, through bacterial infections, can contribute to cancer development and progression through chronic inflammation, inhibition of cell-death, and the release of carcinogenic substances. Microbial shifts driven by prolonged inflammation resulting from chronic oral diseases can escalate dysbiosis and promote neoplastic changes. Despite growing interest, oral microbiome-cancer-axis remains an emerging field. Current research focuses on a small number of microorganisms and associated virulence factors within the tumor-microenvironment, underscoring the need for more comprehensive, systems-level analyses. In this review, we conducted a comprehensive search of PubMed and Google Scholar (2019-2025), to identify and screen studies examining the association between bacterial infections and oral cancer. This review aims to examine and summarize the existing literature to elucidate risks and potential mitigation strategies associated with concurrent bacterial infections in oral cancer. In conclusion, more comprehensive, large-scale, and interdisciplinary studies are needed to understand the microbial influence on cancer, its impact on therapeutic responses, use of probiotics to enhance chemosensitivity and targeted-antibiotic therapy to reduce pathogenic load.
    Keywords:  Fusobacterium nucleatum; Oral microbiome; Porphyromonas gingivalis; inflammatory pathways; oral cancer; probiotic therapy; tumor microenvironment
    DOI:  https://doi.org/10.1080/17460913.2025.2606754
  10. Int J Pharm. 2025 Dec 20. pii: S0378-5173(25)01337-7. [Epub ahead of print]689 126500
      Wound healing is a complex process. Due to the influence of multiple factors on its progression, its management and treatment remain highly challenging. Pressure ulcers are a type of chronic wounds caused by prolonged pressure on the skin. In recent years, significant efforts have been devoted to developing novel therapies for the prevention and treatment of pressure ulcers. However, conventional drugs and clinical therapies are often limited in efficacy, fail to achieve optimal therapeutic outcomes. Consequently, novel biomaterials have been developed, with particular attention given to their ability to enhance the performance of drugs. This article outlines the healing process of pressure ulcers and summarizes the current clinical strategies for their prevention and treatment. It further reviews novel biomaterials for pressure ulcer management, focusing on their intrinsic therapeutic properties and their role in enhancing drug delivery. This review aims to contribute to future advances in the prevention and treatment of pressure ulcers.
    Keywords:  Biomaterials; Clinical therapy; Drug-loaded biomaterials; Pressure ulcers; Promoting effect
    DOI:  https://doi.org/10.1016/j.ijpharm.2025.126500
  11. Undersea Hyperb Med. 2025 Fourth Quarter;52(4):52(4): 641-668
      Chronic refractory osteomyelitis, according to the Centers for Medicare & Medicaid Services' (CMS) National Coverage Determination (NCD) 20.29, is an identified condition covered for treatment with adjunctive hyperbaric oxygen (HBO₂) therapy. Within the NCD (20.29) chronic refractory osteomyelitis is outlined as being unresponsive to conventional medical and surgical management [1]. From a practical perspective, patients can be appropriately diagnosed with chronic refractory osteomyelitis when they demonstrate no significant improvement or demonstrate worsening of the underlying osteomyelitis despite 30 days of combined conventional surgical and medical treatment that included systemic antimicrobial therapy. To date, no conclusive randomized clinical trials examining the effects of HBO₂ therapy on refractory osteomyelitis exist. Additionally, many of the initial studies that resulted in positive outcomes were conducted in hospital settings safeguarding compliance, and thus, not unexpectedly, the outcomes have not translated exactly to the outpatient clinic setting. Nonetheless, based on a comprehensive review of the scientific literature, the addition of HBO₂ therapy to routine surgical and antibiotic treatment of previously refractory osteomyelitis appears to be both safe and ultimately improves infection resolution rates. In most cases, the best clinical results are obtained when HBO₂ treatment is administered concomitantly with culture-directed antibiotics and initiated soon after clinically indicated surgical debridement. In situations where extensive surgical debridement or removal of fixation hardware is relatively contraindicated (i.e., cranial, spinal, sternal, or pediatric osteomyelitis), a trial of systemic culture-directed antibiotics and HBO₂ therapy prior to undertaking more than limited surgical interventions provides a reasonable prospect for osteomyelitis cure.
  12. Nurs Rep. 2025 Nov 26. pii: 417. [Epub ahead of print]15(12):
      Objective: This study aims to validate a referral model for specialised nursing consultation in the treatment of patients with complex wounds. Methods: A sequential mixed-methods design was used. First, a focus group with national wound care experts was conducted to identify and discuss potential referral indicators based on current clinical practice and the existing literature. The preliminary criteria were then evaluated and refined through a two-round Delphi survey involving a multidisciplinary panel of specialists. Consensus was defined as ≥70% agreement among participants. Results: Fourteen referral criteria achieved expert consensus, with several, such as the need for advanced therapies, multidisciplinary management, and the presence of peripheral vascular disease, reaching over 90% agreement. The most frequently prioritised indicators for referral included wound complexity (exposure of fascia or surgical material, presence of non-viable tissue, or associated vascular pathology) and the need for innovative advanced therapies (e.g., negative-pressure wound therapy, topical oxygen therapy). Conclusions: This validated set of referral criteria offers a structured, evidence-informed tool to support timely and appropriate referral to specialised nursing consultation, enhancing consistency, quality, and efficiency in wound management. Beyond clinical utility, these criteria may serve as a foundation for national referral policies, interprofessional collaboration, and future digital decision-support systems aimed at optimising complex wound care.
    Keywords:  Delphi study; complex wounds; referral criteria; specialist nursing; wound care pathways
    DOI:  https://doi.org/10.3390/nursrep15120417
  13. Biochim Biophys Acta Rev Cancer. 2025 Nov;pii: S0304-419X(25)00227-6. [Epub ahead of print]1880(6): 189485
      Bacteriophages are viruses infecting bacterial cells; therefore, their application in cancer research may initially appear counterintuitive. Nevertheless, bacteriophages have been employed in the development of numerous advanced biotechnological tools, which has led to the emergence of multiple approaches utilizing them for improved cancer diagnostics and novel therapeutic strategies. Unlike other recently published reviews in this field, this paper does not emphasize technological principles or focus on specific cancer type. Instead, we provide a broad overview of innovative concepts and highlight recent advances in the use of bacteriophages in anti-cancer research. In particular, we discuss their roles in: (i) early cancer diagnosis and detection of tumorigenic mutations, (ii) elimination of bacteria that promote carcinogenesis and modulation of the microbiome influencing tumor growth, (iii) development of anti-cancer vaccines, (iv) modulation of cancer-related immune responses, (v) targeted delivery of anti-cancer drugs, and (vi) genetic modification of cancer cells through therapeutic DNA delivery.
    Keywords:  Anticancer therapies; Bacteriophages; Cancer diagnosis; Phage display technology
    DOI:  https://doi.org/10.1016/j.bbcan.2025.189485
  14. Pol J Microbiol. 2025 Dec 01. 74(4): 471-483
      This non-interventional study was conducted at three cystic fibrosis (CF) treatment centers in Poland from August 2022 to July 2023. The aim was to assess the etiology of bacterial infection and evaluate antimicrobial susceptibility in CF patients. Prevalent pathogens were identified and their in vitro susceptibility to commonly prescribed antibiotics was assessed, highlighting potential needs in CF antibiotic therapy. Results indicated that Staphylococcus aureus was the most frequently isolated strain and was highly susceptible to tigecycline, linezolid, vancomycin, co-trimoxazole, and ceftaroline. Pseudomonas aeruginosa, the second most common strain, was susceptible to colistin, ceftazidime/avibactam, and tobramycin but exhibited high resistance to ciprofloxacin and cefepime. Coinfections of S. aureus and P. aeruginosa were notably more prevalent in adult CF patients. Although bacterial diversity was comparable between adults and children, limited sample sizes for specific species constrained the statistical analysis. Notably, comprehensive resistance data were lacking for most samples; however, many P. aeruginosa strains were classified as multidrug-resistant. Additionally, methicillin-resistant S. aureus and extended-spectrum β-lactamase-producing strains of Enterobacter cloacae and Klebsiella species were identified. This study highlights the importance of ongoing surveillance of bacterial pathogens and their resistance patterns in CF patients, as such information is essential for optimizing antibiotic therapy and improving clinical outcomes.
    Keywords:  antimicrobial susceptibility; bacterial infections; cystic fibrosis; multidrug resistance; respiratory pathogens
    DOI:  https://doi.org/10.33073/pjm-2025-040
  15. Gut Microbes. 2026 Dec 31. 18(1): 2604867
      The human gut microbiome plays a critical role in modulating pharmacological and toxicological responses to medications. With a gene pool vastly exceeding that of the human host, the gut microbiome acts as a metabolically active organ capable of transforming, inactivating, or accumulating drugs. This review explores the bidirectional interplay between prescription medicines and the gut microbiome, encompassing three key mechanisms: direct biotransformation by microbial enzymes, indirect modulation of host metabolism and signaling pathways, and drug bioaccumulation within microbial cells. Particular attention is given to six major drug classes: immunotherapeutics, chemotherapeutics, antidepressants, statins, hypoglycemics, and antihypertensives. The ways in which individual microbial profiles can influence therapeutic outcomes are also reviewed. We examined how common non-antibiotic pharmaceuticals can significantly alter microbial diversity and promote antimicrobial resistance. Strategies to enhance drug efficacy through microbiome modulation, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), are critically assessed. Experimental models ranging from in vitro batch and chemostat systems to animal and clinical studies are compared in terms of their utility for studying drug‒microbiome interactions. Finally, emerging evidence suggesting the gut microbiota composition may serve as a predictive biomarker for personalized medicine and therapeutic success is highlighted. Understanding and harnessing the complex interrelationships between medicines and microorganisms could offer novel avenues to optimize treatment outcomes and mitigate adverse drug effects.
    Keywords:  Drug metabolism; gut; microbiome; microbiome modulation; personalized medicine; pharmaceuticals
    DOI:  https://doi.org/10.1080/19490976.2025.2604867
  16. J Antimicrob Chemother. 2025 Dec 22. pii: dkaf470. [Epub ahead of print]
       BACKGROUND: Development of clinical decision support systems (CDSS) has been ongoing for over 60 years, more recently leveraging technologies such as artificial intelligence (AI) and machine learning (ML). Intelligent CDSS addressing different stages of the infection management process offer potential advantages in interpreting complex data and guiding clinical decision-making.
    OBJECTIVES: We outline the current applications of AI-driven CDSS across the continuum of bacterial infection management, from prevention and diagnosis to antibiotic prescribing and treatment individualization. We discuss the main limitations hindering their translation into clinical practice, as well as opportunities to improve their development to better meet clinical needs.
    METHODS: References for this review were identified through searches of PubMed, Google Scholar, bioRxiv and arXiv up to March 2025 by use of a combination of ML, decision-making and bacterial infection keywords.
    KEY FINDINGS: AI-CDSS studies increasingly leverage multimodal electronic health record (EHR) data, with most adopting lower-complexity models that perform well on structured data, particularly when supported by effective feature engineering. Despite efforts to develop accurate AI-driven systems, some of which achieve clinician-level accuracy in solving diagnostic and prescribing tasks, AI-CDSS have largely failed to integrate into clinical settings. Their adoption faces challenges related to the narrow scope of the defined medical task, failure to consider stakeholder workflow and lack of proper evaluation frameworks.
    CONCLUSION: There is a need to shift CDSS development towards a more adaptive and holistic approach that recognizes the continuous nature of the decision-making process in infection management. Comprehensive AI-powered platforms that can model infection dynamics could improve antibiotic stewardship and help tackle the global health emergency of antimicrobial resistance.
    DOI:  https://doi.org/10.1093/jac/dkaf470
  17. Gastroenterology. 2025 Dec 23. pii: S0016-5085(25)06015-9. [Epub ahead of print]
    Microbiome Data Provision Group
       BACKGROUND & AIMS: Few studies describe gut microbiome signatures in treatment-naïve new-onset inflammatory bowel disease (IBD). We present a novel secondary bioinformatic reanalysis of sequence outputs mapped to the latest microbial taxonomy.
    METHODS: MEDLINE and Embase searches were performed for microbiome studies in treatment-naïve IBD. Appraisal was completed with Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E). Available 16S ribosomal RNA sequence data sets were downloaded and missing data sets requested. Integrated data were run through a unified QIIME2 bioinformatics pipeline. Multivariable models adjusting for methodologic differences were developed using MaAsLin2.
    RESULTS: There were 36 eligible studies; 18 contributed to bioinformatic reanalysis and 24 to supplementary meta-analysis. Samples from 1743 patients were included, comprising 678 from individuals with Crohn's disease (CD), 399 with ulcerative colitis (UC), 130 healthy controls (HCs), and 405 symptomatic controls (SCs); 990 of which were biopsy samples. Alpha diversity was reduced: feces-pediatric UC vs SCs, adult CD and UC vs HCs, and pediatric SCs vs HCs; pediatric biopsy samples-CD vs SCs, CD vs UC, and UC vs SCs. Beta diversity demonstrated clear distinctions between fecal and mucosal biopsy communities, least evident in UC, in addition to community separation by geography. Multivariate modeling revealed depletion of anaerobic and enrichment of aerobic and facultative anaerobic bacteria, alongside enrichment of oral genera across both CD and UC.
    CONCLUSIONS: Core microbial perturbations at onset of CD and UC are depletion of anaerobes and enrichment of oxygen-tolerant, orally associated bacteria. As we place greater emphasis on early diagnosis and prediction of IBD risk, this finding may support innovative diagnostic approaches. Microbiome-targeted intervention and alteration of luminal oxygen availability may offer novel therapeutic avenues for new-onset patients and identified high-risk groups.
    Keywords:  Crohn’s Disease; Microbiota; Treatment-Naïve; Ulcerative Colitis
    DOI:  https://doi.org/10.1053/j.gastro.2025.09.014
  18. Adv Sci (Weinh). 2025 Dec 27. e22437
      The escalating public health security crisis caused by pathogenic microorganisms and the worsening antibiotic resistance urgently demand the development of antimicrobial materials with high efficiency and safety. Covalent organic frameworks (COFs) exhibit significant potential in photocatalytic antibacterial applications, but face challenges such as insufficient biosafety and difficulties in application translation. In this work, we first report two metformin-based photoactive cationic MCOFs engineered for synergistic functionality and safety. They exhibit broad-spectrum light absorption, efficient charge separation, and generate multiple ROS via Type I/II photodynamic, achieving >99 % inactivation of bacteria/viruses. Excellent biocompatibility with LD50 >5000 mg/kg is confirmed. Mechanistic studies based on molecular dynamics (MD) simulation and transcriptome results revealed a triple synergistic antibacterial pathway involving membrane targeting, ROS attack, and metabolic interference. Furthermore, we fabricated a COF/thermoplastic polyurethane (TPU) composite functional membrane, which exhibits >99 % antibacterial and antiviral efficiency, along with a notable 98.3 % inhibition rate against methicillin-resistant Staphylococcus aureus (MRSA). This study not only provides a new design strategy for MCOFs with synergistically enhanced functionality and biosafety, but also offers a promising material platform for biomedical applications such as anti-infection protection, wound healing, and the treatment of drug-resistant bacterial infections.
    Keywords:  biosafety; covalent organic frameworks; metformin; photoactivity
    DOI:  https://doi.org/10.1002/advs.202522437
  19. Front Microbiol. 2025 ;16 1713775
       Background/aims: The diverse composition of the gut microbiome is vital for human health, influencing digestion, immune regulation, and disease resistance. While higher diversity is generally associated with resilience, reduced and excessive diversity can lead to health issues.
    Methods: This paper introduces the Constrained Disorder Principle (CDP) as a new framework for understanding microbial diversity.
    Results: The CDP emphasizes the significance of maintaining variability within certain boundaries to sustain ecosystem stability and promote health. It considers intra- and inter-individual variability, illustrating how microbial ecosystems adapt throughout different life stages, genetic backgrounds, and environmental exposures. Integrating CDP-based artificial intelligence systems may enable the establishment of personalized diversity thresholds, predict dysbiosis, and refine interventions such as probiotics, prebiotics, fecal microbiota transplantation, and customized dietary strategies. CDP-driven platforms enhance therapeutic precision by utilizing variability induction, feedback loops, and microbial signature analysis to optimize diversity goals and identify actionable biomarkers.
    Conclusion: This platform can pave the way for adaptive, individualized disease prevention and treatment strategies, bridging the gap between microbial ecology and precision medicine. It provides a powerful tool for harnessing the therapeutic potential of gut microbial diversity to enhance human health.
    Keywords:  artificial intelligence; digital health; gut diversity; microbiome; variability
    DOI:  https://doi.org/10.3389/fmicb.2025.1713775
  20. Cureus. 2025 Nov;17(11): e97668
      Antimicrobial resistance (AMR) constitutes a critical challenge in contemporary healthcare. The proliferation of resistant bacteria threatens the safety of surgical procedures, cancer chemotherapy, and critical care worldwide. Increased mortality from drug-resistant infections results from both microbial adaptation and systemic deficiencies in surveillance, stewardship, and innovation. Although global awareness has increased, the development of new antibiotics remains limited, and disparities in access to effective therapies continue. Addressing this crisis requires a unified One Health approach that integrates human, animal, and environmental health. This editorial analyzes the scope of AMR, the economic and regulatory factors driving the decline in antibiotic innovation, and the urgent reforms needed to sustain modern medical practice.
    Keywords:  antibiotic stewardship; antimicrobial resistance; drug-resistant infections; global health; one health
    DOI:  https://doi.org/10.7759/cureus.97668
  21. Curr Opin Biotechnol. 2025 Dec 19. pii: S0958-1669(25)00163-6. [Epub ahead of print]97 103419
      Biofoundries are transforming biotechnology by automating design-build-test-learn (DBTL) cycles that accelerate biological design and innovation. While globally recognized as strategic infrastructures for the bioeconomy, they remain underrepresented in Latin America. This perspective highlights opportunities and challenges for establishing biofoundries across the region, emphasizing the need for open-access infrastructures, interdisciplinary networks, sustainability-assisted developments, and regulatory convergence. We discuss the advancement of integrated biofoundry models that combine multi-omics and synthetic biology approaches with sustainability assessments and bioprocess scale-up capabilities. This integrative framework, spanning from bioprospection to bioprocess scale-up, offers a key strategy to bridge biodiversity and industrial innovation, serving as a potential blueprint for expanding biofoundry initiatives across Latin America. Harnessing the regional biodiversity, scientific capacity, and growing innovation networks can establish a collaborative, sustainable biofoundry landscape capable of converting biological resources into high-value biotechnological solutions to address global challenges.
    DOI:  https://doi.org/10.1016/j.copbio.2025.103419
  22. Med Int (Lond). 2026 Jan-Feb;6(1):6(1): 5
      Since its inception as rule-based programs, artificial intelligence (AI) has developed into machine learning and deep learning systems that utilize the enormous volumes of clinical data currently accessible. The aim of the present review was to discuss the role of AI in modern clinical practice and to highlight the opportunities and challenges that lie ahead by combining the results of recent research. AI tools provide physicians with decision support and prediction models, directs robotic procedures and surgical planning, supports radiologists, pathologists, dermatologists and ophthalmologists with image analysis, and aids in the delivery of more individualized care in cardiology and precision medicine. These developments are boosting precision, optimizing daily tasks and providing patients with more individualized treatment. In practice, this could include imaging systems that prioritize patients who are most at risk or prediction technologies that help physicians allocate resources and reduce unnecessary workload. However, there are still critical obstacles to overcome. The biases of the training data may be reflected in the algorithms, which could exacerbate already-existing disparities. Since many models operate as 'black boxes', it can be challenging to understand their logic, which raises questions about accountability, ethics and trust. Clinical standards and regulations are still lagging behind technology, and incorporating AI into busy healthcare systems can be difficult and costly. Achieving its promise will require careful implementation, rigorous validation and sustained collaboration among clinicians, data scientists, engineers, ethicists and policymakers for safe adoption in clinical practice.
    Keywords:  artificial intelligence; cardiology; clinical decision support; deep learning; digital pathology; healthcare ethics; machine learning; medical imaging; precision medicine; robotic surgery
    DOI:  https://doi.org/10.3892/mi.2025.289
  23. BMC Microbiol. 2025 Dec 23.
       AIMS: Oral microbiome transplantation (OMT) involves transferring microbiota from donor to recipient. However, selecting suitable donors remains challenging due to a lack of standardised guidelines. This study developed a novel super donor assessment tool (SDAT) combining a multi-criteria decision-making (MCDM) process and an analytical hierarchical process (AHP) to identify OMT "super donors" for dental caries prevention.
    METHODS: This cross-sectional study used four sequential screening phases with data from 93 healthy participants, capturing socio-demographics, lifestyle, dietary and oral health behaviours. The SDAT employed MCDM, AHP, combining criteria with normalised and weighted ranks to establish the top 10 donors for three models: "Optimal donor" (Model 1), "Ideal donor" (Model 2), and "Sub-optimal donor" (Model 3). Donor plaque samples underwent 16S ribosomal RNA amplicon sequencing for microbial profiling, examining alpha and betadiversity, differential abundance, and network analysis.
    RESULTS: Alpha diversity analysis showed significant differences among groups (Kruskal-Wallis p < 0.001), with Model 1 showing the lowest diversity and Model 3 the highest. Beta diversity analysis using Permutational Multivariate Analysis of Variance revealed significant differences in microbial community composition (R² = 0.19, p = 0.001). Differential abundance analysis (False Discovery Rate < 0.05, controlling for age and sex) identified health-associated genera (Neisseria, Lautropia, Streptococcus, Veillonella) in Model 1, whereas Model 3 showed higher levels of disease-associated taxa (Treponema, Capnocytophaga). Network analysis revealed that Model 1 was organised around Actinomyces and Prevotella, Model 2 around Rothia and Haemophilus, and Model 3 was dominated by pathogenic taxa.
    CONCLUSION: SDAT provides a systematic, transparent framework for super-donor selection, ensuring precision and reproducibility in donor rankings. The scoring system standardises the donor selection process, the effectiveness of donor screening, and reduces the risk of adverse events for OMT.
    Keywords:  Analytical hierarchy process; Decision making; Decision support model; Microbiome; Microbiota; Oral health
    DOI:  https://doi.org/10.1186/s12866-025-04630-z
  24. Bioelectrochemistry. 2025 Dec 18. pii: S1567-5394(25)00307-X. [Epub ahead of print]169 109204
      Wound treatment costs are estimated to reach over 20 billion USD in the case of chronic wounds. Hence, the methods of monitoring the stage of healing are of high importance. It should be emphasized that traditionally applied methods, including visual examination as well as bacterial cell cultivation, are not precise and might be lengthy. Therefore, there is a great need for elaboration of novel approaches in controlling the healing process as well as enhancing it through novel drug delivery systems that can be realized using wearable sensors. Such an approach contributes to the minimization of patient discomfort and enables the live determination of the actual stage of wound healing. Herein, we present a critical review of current examples of such devices (presented from 2021 to 2025), as well as the characterization of basics such as the wound healing process and materials applied for sensors' fabrication. In the final part, we depict the challenges, including signal drift or nonspecific adsorption on the sensor surface, and future perspectives of the application of such noninvasive sensors in clinical diagnostics.
    Keywords:  Biosensors; Electrochemistry; Wearables; Wound dressing; Wounds
    DOI:  https://doi.org/10.1016/j.bioelechem.2025.109204
  25. Dent J (Basel). 2025 Dec 12. pii: 595. [Epub ahead of print]13(12):
      Background: Periodontitis and oral dysbiosis have been linked to systemic inflammation and carcinogenesis. Among oral pathogens, Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) are biologically plausible contributors to colorectal cancer (CRC) via inflammatory and immunomodulatory pathways. However, the magnitude and consistency of these associations remain uncertain. Objective: To evaluate whether periodontitis and key oral pathogens are associated with CRC risk and prognosis through a systematic review, meta-analysis, and trial sequential analysis (TSA). Methods: We searched PubMed, Scopus, and Web of Science from inception to December 2024 following PRISMA 2020. Eligible observational studies assessed periodontitis exposure or detection of oral bacteria in relation to CRC incidence or survival. Effect estimates (RRs/HRs) were log-transformed and pooled using random-effects models; heterogeneity was quantified with I2. TSA was conducted to appraise information size and the stability of the primary association. Risk of bias was evaluated with ROBINS-I/QUIPS as appropriate. PROSPERO: CRD420251168522. Results: Five studies evaluating periodontitis/oral-pathogen exposure and CRC incidence yielded a 70% higher risk (HR = 1.70; 95% CI: 1.33-2.19; I2 = 0%). Detection of Fn was associated with approximately threefold higher risk of CRC (RR = 3.20; 95% CI: 1.76-5.82; p < 0.001). Pg presence was linked to worse overall survival (HR ≈ 2.4; p < 0.01). TSA suggested that the accrued evidence for the primary incidence association is likely sufficient to reduce random errors; nevertheless, interpretability is constrained by the small number of observational studies and between-study differences in exposure and outcome ascertainment. Conclusions: Current evidence indicates that periodontitis and oral pathogens-particularly Fn and Pg-are significantly associated with CRC development and progression. These findings support the clinical relevance of the oral-gut axis and underscore oral health as a potentially modifiable factor in cancer prevention. Further large, well-designed prospective cohorts and mechanistic studies are warranted to strengthen causal inference.
    Keywords:  Fusobacterium nucleatum; Porphyromonas gingivalis; colorectal neoplasms; gastrointestinal microbiome; oral microbiome; periodontitis
    DOI:  https://doi.org/10.3390/dj13120595
  26. Infect Dis Clin North Am. 2025 Dec 23. pii: S0891-5520(25)00103-5. [Epub ahead of print]
      Carbapenem-resistant enterobacterales (CRE) remain a major clinical and public health concern, with limited treatment options. Given the heterogeneity in resistance mechanisms, infection syndromes, and host factors, selecting optimal therapy requires an individualized approach. A review of treatment guidelines, clinical studies, and in vitro data supports the use of ceftazidime-avibactam for KPC- and OXA-48-like carbapenemase producers, and ceftazidime-avibactam with aztreonam (or aztreonam-avibactam) for metallo-β-lactamases. For carbapenemase-producing CRE, cefiderocol may also be considered if susceptibility is confirmed. Where possible, colistin and polymyxin B should be avoided due to toxicity and lack of robust clinical data.
    Keywords:  Antimicrobial resistance; Appropriate antibiotics; Bacteraemia; Carbapenem-resistance; Carbapenemase; Enterobacterales
    DOI:  https://doi.org/10.1016/j.idc.2025.11.009
  27. Front Pharmacol. 2025 ;16 1738213
      
    Keywords:  antibacterial strategy; foundational research; therapeutic design; wound healing; wound management
    DOI:  https://doi.org/10.3389/fphar.2025.1738213
  28. ArXiv. 2025 Dec 18. pii: arXiv:2411.01098v2. [Epub ahead of print]
      Advancements in artificial intelligence (AI) have transformed many scientific fields, with microbiology and microbiome research now experiencing significant breakthroughs through machine learning applications. This review provides a comprehensive overview of AI-driven approaches tailored for microbiology and microbiome studies, emphasizing both technical advancements and biological insights. We begin with an introduction to foundational AI techniques, including primary machine learning paradigms and various deep learning architectures, and offer guidance on choosing between traditional machine learning and sophisticated deep learning methods based on specific research goals. The primary section on application scenarios spans diverse research areas, from taxonomic profiling, functional annotation \& prediction, microbe-X interactions, microbial ecology, metabolic modeling, precision nutrition, clinical microbiology, to prevention \& therapeutics. Finally, we discuss challenges in this field and highlight some recent breakthroughs. Together, this review underscores AI's transformative role in microbiology and microbiome research, paving the way for innovative methodologies and applications that enhance our understanding of microbial life and its impact on our planet and our health.
  29. Future Microbiol. 2025 Dec 26. 1-22
      Polymicrobial infections, involving the simultaneous presence of two or more microbial species at a single infection site, are an emerging clinical challenge with increasing incidence across a wide range of healthcare settings. These infections often result in more severe disease outcomes compared to monomicrobial infections due to complex interspecies interactions that enhance microbial survival, virulence, and resistance. One of the most concerning aspects of polymicrobial infections is their strong association with multidrug resistance (MDR). The Synergistic interactions among microbial species enhance biofilm formation, impede immune clearance, and reduce antimicrobial penetration and efficacy, contributing to therapeutic failure and chronic infection. The management of polymicrobial infections is further complicated by diagnostic limitations, as standard culture-based techniques often fail to capture the full microbial diversity present at infection sites. Despite their clinical relevance, drug discovery efforts still rely largely on mono-species biofilm models that overlook the interactions, metabolic cooperation, and resilience of polymicrobial systems. This review outlines advances in polymicrobial biofilm research including improved models, high-throughput screening, and omics insights while emphasizing remaining gaps in spatial organization and host - pathogen dynamics. Addressing these gaps and adopting polymicrobial perspectives will be essential for identifying new therapeutic targets and improving outcomes in biofilm-associated infections.
    Keywords:  Multispecies biofilm models; co-infection; drug discovery platforms; microbial synergy; omics approaches; organon-chip
    DOI:  https://doi.org/10.1080/17460913.2025.2604691
  30. Undersea Hyperb Med. 2025 Fourth Quarter;52(4):52(4): 571-575
       Introduction: A chronic leg ulcer is a serious complication of sickle cell anemia. The ulcers are treatment- resistant, recur frequently, and are associated with more severe disease. Treatment options for chronic leg ulcers in patients with sickle cell disease are limited. Hyperbaric oxygen (HBO₂) therapy is a promising therapy for the management of sickle cell chronic leg ulcers as it relieves hypoxia, promotes angiogenesis, and reduces wound inflammation.
    Case: A 35-year-old male with sickle cell anemia with a chronic leg ulcer for one year, despite regular wound dressing and antibiotics, was then successfully managed through HBO₂ therapy followed by skin grafting.
    Conclusion: HBO₂ therapy was effective in this case and has also shown effectiveness as an adjunct therapy in the management of sickle cell-related chronic leg ulcers in other case reports. This supports the need for further research in this area.
    Keywords:   chronic leg ulcer; hyperbaric oxygen therapy; sickle cell anemia
  31. Geriatrics (Basel). 2025 Dec 02. pii: 158. [Epub ahead of print]10(6):
       BACKGROUND: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI leads to higher mortality and prolonged, debilitating illness.
    CASE PRESENTATIONS: This article presents two patients, aged over 80 years old, who developed recurrent CDI causing complicated and prolonged treatment courses. Patient 1 required an extended course of antibiotics for treatment of discitis and a congruent psoas abscess. Patient 2 developed CDI after multiple short courses of antibiotics for urinary tract infections (UTIs) in the context of multiple comorbidities. Both patients experienced three distinct episodes of CDI and were treated in collaboration with microbiology specialists. Following the third episode, both were successfully treated with oral capsule faecal microbiome transplants (FMTs). Their cases highlight the challenge of balancing systemic antibiotic use against CDI risk.
    DISCUSSIONS: These cases underscore known risk factors for recurrent CDI, including advanced age and prolonged antibiotic exposure. Recurrence rates in patients over 65 can reach 58%. The British Society of Gastroenterology and Healthcare Infection Society support the use of FMTs in recurrent cases. Environmental decontamination, including terminal cleaning with sporicidal agents, is critical in reducing reinfection in hospital settings.
    CONCLUSIONS: Recurrent CDI in elderly patients reflects a complex interplay between infection control and managing comorbidities. New guidelines suggest that FMTs can significantly reduce morbidity and mortality. These cases emphasise the need for individualised, multidisciplinary care, adherence to guidelines, and further research to improve safe, effective CDI management in older adults.
    Keywords:  C. diff recurrence; C. diff toxin; Clostridioides difficile; antibiotics; faecal microbiome transplant; geriatrics; infection control; infectious diseases; multimorbidity; older adults
    DOI:  https://doi.org/10.3390/geriatrics10060158
  32. Essays Biochem. 2025 Dec 23. pii: EBC20254001. [Epub ahead of print]69(6):
      
    Keywords:  Dysbiosis; Gut Microbiome; Gut Microbiota; Microbial Metabolites
    DOI:  https://doi.org/10.1042/EBC20254001