bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–04–12
35 papers selected by
Luca Bolliger, lxBio



  1. Indian J Med Res. 2026 Feb;pii: 10.25259/IJMR_2923_2025. [Epub ahead of print]163(2): 139-165
      Background and objectives Amidst the setting of a worldwide threat posed by antimicrobial resistance, bacteriophages have emerged as novel antibiotic alternatives. This scoping review was conducted to systematically survey and categorise bacteriophage research conducted in India, focusing on explicit implications for human health. Methods We conducted a scoping review according to PRISMA-ScR guidelines. We searched five databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) without any date restrictions through June 2025. Studies were included if they presented original research on bacteriophages or phage therapy in Indian settings (human, animal, orenvironmental). Data were tabulated on a pre-designed form and classified by application area, study type, and outcomes. Results The initial search of the databases led to 4,756 studies, and ultimately, 111 were included. Studies were predominantly from the laboratory setting, with very few clinical and translational studies. The majority of the included study types were animal models of efficacy and in vitro phage characterisation. Very few were conducted with human subjects or clinical trial designs. Gaps of particular concern are a lack of regulatory framework, clinical trials, pharmacokinetic-pharmacodynamic studies, synthetic biology methods, and One Health integrated surveillance systems. Interpretation and conclusion Bacteriophage research in India is growing but is still underdeveloped in translational areas. Closing the listed shortcomings and keeping the pace with international innovations, such as engineered phages, standardised formulations, and clinical validations, will be critical to realise the full potential of phage therapy in India.
    Keywords:  Antimicrobial resistance; Bacteriophage; India; One Health; Phage research
    DOI:  https://doi.org/10.25259/IJMR_2923_2025
  2. Front Microbiol. 2026 ;17 1762768
      Phage endolysins are increasingly recognized as alternatives to antibiotics for mitigating the growing threat of antimicrobial resistance. Since their initial identification in the 1950s, phage endolysins have been extensively demonstrated to effectively combat bacterial infections in animal models and human patients. Although phage endolysins have completed Phase II and III clinical trials, potential obstacles and challenges associated with their large-scale use remain largely undefined. This review examines the potential of phage endolysins and the challenges they face in addressing infections caused by antibiotic-resistant bacteria in the future. We conducted a comprehensive overview of the historical development, bactericidal mechanisms, clinical progress, and resistance of phage endolysins. The information presented herein may facilitate the design of novel, potent endolysins and provide strategic insights for addressing phage endolysin resistance.
    Keywords:  antibiotic alternatives; antimicrobial resistance; phage endolysin resistance; phage endolysins; phage therapy
    DOI:  https://doi.org/10.3389/fmicb.2026.1762768
  3. J Oral Microbiol. 2026 ;18(1): 2656084
       Background: Periodontitis and inflammatory bowel disease (IBD) are chronic inflammatory conditions of the oral and gastrointestinal tracts that exhibit bidirectional microbial and immunological crosstalk.
    Objective: Aimed at elucidating the bidirectional crosstalk between periodontitis and IBD at both microbiological and immunological levels and evaluate related therapeutic interventions, this review comprehensively summarizes recent evidence on their interaction via the oral-gut-bone axis, focusing on microbial ecology, host responses, and innovative therapies.
    Design: Distinct yet overlapping dysbiotic signatures are observed in both diseases, with periodontal pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum capable of translocating to the gut and perturbing intestinal homeostasis, while gut inflammation reciprocally reshapes the oral microbiome. Mechanistic links include a spectrum of convergent pathways: (i) microbial metabolites-short-chain fatty acids, choline metabolites, indole derivatives, polyamines, and bile acids-that modulate barrier integrity and immune responses; (ii) shared immune cells and inflammatory mediators driving mucosal damage at both sites; (iii) bacterial extracellular vesicles (BEVs) and lysine lactylation (Kla)-mediated signaling; and (iv) oxidative stress, iron metabolism dysregulation, and ferroptosis contributing to tissue destruction.
    Results: Therapeutic strategies targeting this axis encompass bidirectional interventions: periodontal and IBD treatments that mutually influence oral and gut health, natural anti-inflammatory and antimicrobial compounds, probiotics and prebiotics, oral and fecal microbiota transplantation, and emerging bacteriophage therapy. Critically, the clinical translation of collaborative dentistry-gastroenterology management is highlighted as a promising avenue for integrated care.
    Conclusions: By integrating findings across microbial ecology, host response, and therapeutic innovation, this review provides a comprehensive framework for understanding and targeting the periodontitis-IBD axis.
    Keywords:  Periodontitis; inflammation; inflammatory bowel disease; metabolism; oral-gut axis; therapeutics
    DOI:  https://doi.org/10.1080/20002297.2026.2656084
  4. Npj Viruses. 2026 Apr 04. pii: 21. [Epub ahead of print]4(1):
      Traditional bacteriophage methods measure population averages rather than individual particle variation. This perspective advocates for approaches to quantify trait variation in phage particles. Emerging techniques in optical microscopy and flow cytometry can reveal previously-masked phenotypic heterogeneity, offering unprecedented insights across phage infection cycle: binding kinetics, genome entry, replication, coinfection dynamics, and particle stability. This shift from population averages to individual variation represents a critical frontier for phage biology and biotechnology.
    DOI:  https://doi.org/10.1038/s44298-026-00187-4
  5. Curr Pharm Biotechnol. 2026 Mar 17.
      A diverse microbial community exists within the human oral cavity that plays an essential role in maintaining health or inducing diseases such as dental caries, periodontal disease, and halitosis. Probiotics, live microorganisms that provide health benefits when consumed in adequate amounts, have been found to be promising as a means of modulating the oral microbiome and combating these diseases. This review incorporates present knowledge about the mechanism of probiotic action, including competitive exclusion of pathogens, antimicrobial metabolite production, biofilm disruption, and immune modulation. Efficacy against pathogenic bacteria like Streptococcus mutans and Porphyromonas gingivalis has been proven by prominent probiotic groups Lactobacillus, Bifidobacterium, and Streptococcus, resulting in oral microbial homeostasis. Clinical applications of probiotics include prevention of caries, plaque reduction, and management of gingivitis and periodontitis, with research focusing on strain-specific effects. Emerging trends include precision probiotics tailored to each oral condition, postbiotics as strong alternatives (formerly "strong contenders"), and innovative delivery systems to enhance viability and colonization. The hurdles of strain specificity, regulatory gaps, and inconsistencies of clinical outcome continue. Safety concerns, while rare, represent possible risks of horizontal gene transfer and opportunistic infections in immunocompromised hosts. Future directions lie in genetic modification, new delivery methods, and standard clinical protocols to enhance probiotic function. This review emphasizes the clinical potential of probiotics as adjunctive treatments in oral medicine, with the caveat that further work is needed to overcome current challenges and enhance their therapeutic efficacy.
    Keywords:  Probiotics; microbial modulation.; oral health; oral microbiome; probiotic strain
    DOI:  https://doi.org/10.2174/0113892010421039251206192855
  6. Front Pharmacol. 2026 ;17 1788742
      
    Keywords:  advanced drug delivery systems; chronic wound healing; diabetic foot ulcers; polyherbal and integrative therapies; precision medicine; wound microbiome
    DOI:  https://doi.org/10.3389/fphar.2026.1788742
  7. Future Microbiol. 2026 Feb;21(3): 329-348
      Emergence of drug-resistant bacterial infections, particularly those caused by Klebsiella pneumoniae, represents a growing public health issue. K. pneumoniae is the leading cause of nosocomial infections, associated with diverse diseases and high mortality rates. Its ability to develop multiple resistance mechanisms, including biofilm formation, efflux pump activity, β-lactamase production, enzymatic modification, and porin loss, contributes to its resistance to conventional antibiotics. These challenges urge the ned for novel therapeutics and alternative therapies. While resistance rates remain lower in developed countries, regions in Africa, South Asia, and Middle East report rates exceeding 80%, often due to antibiotic misuse and inadequate regulations. Particularly concerning are novel hypervirulent carbapenem-resistant strains linked to bloodstream infections and high mortality, especially in low- and middle-income countries. Emerging approaches, including fecal microbiota transplantation, might help gut dysbiosis and enhance host immunity against carbapenemase-producing Enterobacterales. Additionally, molecular studies identified cytoplasmic response regulators that promote resistance gene expression and plasmid-mediated transfer, offering prospective therapeutic targets. This review summarizes current knowledge regarding the genetic, molecular, and epidemiological mechanisms of multidrug resistance and virulence in K. pneumoniae, and discusses emerging therapeutic strategies including new β-lactamase inhibitors, bacteriophage and host-directed therapies, in silico therapeutic strategies, and vaccine development.
    Keywords:  Klebsiella pneumoniae; Multi-drug-resistant infections; antibiotic-resistance mechanism; nosocomial infections; plasmid-mediated acquired resistance
    DOI:  https://doi.org/10.1080/17460913.2026.2654374
  8. Hepatol Res. 2026 Apr 10.
      Biliary atresia (BA) remains the most devastating fibro-inflammatory cholangiopathy of infancy. Even after successful Kasai portoenterostomy (KPE), progressive liver fibrosis ultimately dictates long-term outcomes. The "microbiome-gut-liver axis" has fundamentally reshaped our understanding of liver disease pathogenesis, yet critical questions persist regarding how Kasai surgery reconfigures this axis and whether these changes actively contribute to fibrogenesis. This review traces a mechanistic cascade from anatomical remodeling through dysbiosis, metabolic disruption, immune dysregulation, and ultimately liver fibrosis. We examine how Kasai surgery physically reprograms the gut ecosystem through altered biliary-enteric continuity and bile acid circulation; how microbial metabolites-particularly secondary bile acids and short-chain fatty acids-orchestrate hepatic stellate cell behavior and shape the hepatic immune milieu; and how bacterial translocation sustains inflammation through Toll-like receptor signaling. Recent evidence challenging the primacy of TLR4 in long-term progression instead implicates TLR7 as a potential driver, while acknowledging its complex, context-dependent role that may involve both pro-fibrotic and counter-regulatory functions. Building on this foundation, we critically assess emerging intervention strategies-including probiotics, postbiotics, phage therapy, and personalized approaches-weighing translational potential against current evidence gaps and safety considerations. We propose that post-Kasai alterations in the bile acid pool may drive fibrogenesis through synergistic engagement of FXR and TLR pathways (including TLR4 and TLR7), and outline a stratified, dynamic intervention framework for precision microbiome management grounded in multi-omics integration and longitudinal cohort studies. By synthesizing current knowledge while identifying key uncertainties, this review aims to inform both mechanistic investigation and the development of microbiome-targeted adjunctive therapies for BA.
    Keywords:  biliary atresia; kasai procedure; liver fibrosis; microbiome‐gut‐liver axis; secondary bile acids
    DOI:  https://doi.org/10.1111/hepr.70184
  9. J Dent Anesth Pain Med. 2026 Apr;26(2): 109-120
       Background: Although the relationship between gut bacteria and pain is increasingly well understood, research on the role of oral bacteria in pain remains limited. Porphyromonas gingivalis (P. gingivalis), a major pathogen in periodontal disease, is known to drive the progression of infection in the oral cavity, leading to inflammation and tissue destruction. However, unlike other conditions, patients with periodontal disease exhibit variable pain responses. This unique presentation suggests that P. gingivalis exerts multifaceted effects on pain modulation.
    Methods: The bibliographic databases of PubMed, Embase, Google Scholar, and the Cochrane Library were searched for original and reviewed in vitro, animal, and human studies. Key data on pain, inflammation, and neuroimmune pathways were extracted. Studies that did not address pain mechanisms or were limited to non-oral/systemic conditions without a clear link to orofacial pain were excluded.
    Results: This review summarizes the current evidence on how P. gingivalis influences inflammation and pain, highlighting the interactions between its cell wall components (e.g., lipopolysaccharide and fimbriae), metabolic byproducts (e.g., nitric oxide and butyric acid), and the host immune response.
    Conclusion: The diverse pain manifestations in P. gingivalis-induced periodontitis may reflect the different stages of disease. Early pain suppression may result from bacterial immune evasion, wherein therapies adjunctive to scaling and root planing, such as host modulation therapy or gingipain inhibitors, may help restore host immunity and improve clinical outcomes.
    Keywords:  Analgesia; Cytokine; Inflammation; Pain; Porphyromonas gingivalis
    DOI:  https://doi.org/10.17245/jdapm.2026.26.2.109
  10. Int Wound J. 2026 Apr;23(4): e70908
      Chronic wounds, including Diabetic Foot Ulcers (DFUs), Venous Leg Ulcers (VLUs) and Pressure Ulcers (PUs), present significant challenges for the patients, clinicians and healthcare systems. There remains a strong need for novel and effective technologies to accelerate the healing of these wounds. The objective of this prospective, single-arm pilot study was to evaluate the clinical performance of a novel nanofiber wound matrix for the treatment of chronic lower extremity wounds refractory to standard-of-care treatment at a single centre. A total of 15 patients with 15 chronic wounds (5 DFUs, 8 VLUs and 2 PUs) were included in this study. These wounds were non-healing to previous standard-of-care treatments for an average of 4 weeks. They were all treated with the novel nanofiber wound matrix with weekly clinical evaluation and re-application for a total duration of four (4) weeks, per the study protocol. The average wound area reduction (WAR) was 83.6% upon 4 weeks of treatment with the application of the subject wound matrix, as an adjunctive measure to the standard of care. Additionally, seven (7) of the 15 wounds (46.7%) completely healed starting from Week 3, and the average complete healing time was 13.9 days. These results demonstrated accelerated healing effects of the subject wound matrix, when compared to the standard of care reported in literature, where the average WAR was at 62.9% at Week 12, six (6) of the 18 wounds (33.3%) were completely healed within 12 weeks, and the average complete healing time was 49.0 days. These results demonstrated that the subject wound matrix is a safe and effective novel technology in treating chronic wounds, providing significant clinical and economic benefits for patients with various chronic wounds.
    Keywords:  chronic wounds; clinical evaluation; synthetic nanofiber wound matrix
    DOI:  https://doi.org/10.1111/iwj.70908
  11. Adv Wound Care (New Rochelle). 2026 Apr 10. 21621918261438987
       SIGNIFICANCE: Wound healing is an energetically demanding process that is easily disturbed by metabolic dysregulation. Metabolic dysregulation, induced by diabetes, obesity, insulin resistance, and various hormone imbalances, can disrupt each phase of wound repair, increasing the risk of post-operative complications, infection, wound dehiscence, and pathological scarring. We review the current evidence on the role of metabolic regulation in wound healing and highlight clinically relevant considerations for patient care.
    RECENT ADVANCES: Animal and human studies have advanced our understanding of how metabolic pathways influence inflammation, angiogenesis, fibroblast function, and extracellular matrix remodeling during wound healing. These insights have led to the development of novel therapies, including hormone-based topical agents and dressings that both sense and modulate metabolites during wound healing.
    CRITICAL ISSUES: Despite growing recognition of the role of metabolic syndromes and hormonal regulation in wound healing, these factors are insufficiently integrated into clinical wound management. Bridging this gap requires a clear understanding of how metabolic syndromes and hormonal derangements influence healing.
    FUTURE DIRECTIONS: The continued development of treatments that modulate metabolic and hormonal pathways may enhance wound healing while minimizing systemic risk. Clinicians should also integrate local metabolic optimization with medical and lifestyle management to create the optimal wound healing environment for patients.
    Keywords:  androgens; estrogens; fibrosis; gonadal steroid hormones; growth hormone; insulin resistance; obesity; wound healing
    DOI:  https://doi.org/10.1177/21621918261438987
  12. NPJ Biofilms Microbiomes. 2026 Apr 04.
      The lung microbiome is increasingly recognized as a key contributor to the development and progression of chronic airway diseases. While these conditions are typically associated with reduced microbial diversity and pathogen overgrowth, emerging evidence suggests that non-pathogenic bacteria may influence clinical outcomes. However, inconsistent findings across studies have made it difficult to determine their exact role in disease pathophysiology. To identify potentially beneficial members of the lung microbiome, we conducted a systematic review and meta-analysis of clinical studies investigating the association between non-pathogenic bacterial genera or species and clinico-pathological features in individuals with asthma, bronchiectasis, chronic obstructive pulmonary disease and cystic fibrosis. For the meta-analysis, data from different diseases were combined. Our analysis revealed that several bacteria in the lung microbiome were significantly associated with improved lung function and/or reduced airway inflammation across diseases. Although causal relationships cannot be established due to the absence of interventional studies, our findings highlight promising candidates for functional characterization and therapeutic exploration. Considerable heterogeneity in study design and reporting underscores the need for standardized methods and validation in relevant experimental models to advance our understanding of the lung microbiome in chronic airway diseases and inform the development of effective microbiome-based interventions.
    DOI:  https://doi.org/10.1038/s41522-026-00967-z
  13. PLoS Comput Biol. 2026 Apr;22(4): e1014130
      Phages (or bacteriophages) play a critical role in microbial communities, and accurately predicting the hosts of phages is essential for understanding the dynamics of these viruses and their impact on bacterial populations. In the prediction of classification of phage hosts, feature extraction is a critical step that directly affects the accuracy of the predictions. Among the techniques used for feature extraction, k-mers are the most commonly employed method. Although many methods based on k-mers have been proposed, these methods typically use only the frequency information of k-mers as features. However, when frequencies are identical, the frequency information of these k-mers becomes less useful. To address this limitation, we propose a novel method called PhageCGRNet, which not only utilizes the frequency information of k-mers but also incorporates the positional information of k-mers. In our method, we represent each genome sequence as a three-dimensional matrix containing k-mers frequency features and positional features, and then utilize the Convolutional Neural Network model to predict the host category. Specifically, we combine the frequency information of k-mers directly extracted from the sequences with the positional information of k-mers obtained using the Chaos Game Representation method to construct the feature matrix, which serves as the input to the Convolutional Neural Network. We conducted experiments on two benchmark datasets, and compared PhageCGRNet with existing advanced methods for phage host classification. The experimental results demonstrate that PhageCGRNet achieves higher accuracy at both taxonomy levels of species and genus on these two datasets compared to other state-of-the-art methods.
    DOI:  https://doi.org/10.1371/journal.pcbi.1014130
  14. Wiad Lek. 2026 ;79(3): 646-650
       OBJECTIVE: Aim: Periodontitis is a chronic inflammatory condition associated with oral microbiome dysbiosis and the dominance of Gram-negative bacteria such as Porphyromonas gingivalis. It is characterized by progressive destruction of the supporting tissues of the tooth, leading to loss of connective tissue attachment, resorption of the alveolar bone, and, consequently to tooth loosening and loss. If left untreated, it leads to recurrent bacteremia and persistent systemic inflammation. The aim of this study is to discuss the mechanisms linking periodontitis to cardiovascular and neurodegenerative diseases.
    PATIENTS AND METHODS: Materials and Methods: A comprehensive literature review was conducted examining clinical studies, systematic reviews, and meta-analyses assessing the impact of periodontal disease on the development of cardiovascular and neurodegenerative diseases.
    CONCLUSION: Conclusions: Chronic activation of the immune response, oxidative stress, and lipid metabolism disorders promote endothelial dysfunction and the progression of atherosclerosis, increasing the risk of cardiovascular events. At the same time, systemic inflammation can affect the permeability of the blood-brain barrier and exacerbate neuroinflammatory processes, promoting β-amyloid accumulation and the progression of Alzheimer's disease. Analysis of the literature indicates the significant, albeit complex, nature of these relationships, emphasizing the importance of prevention and treatment of periodontal disease as part of comprehensive patient care. The key in the approach to periodontal patients is an interdisciplinary perspective, integrating dentistry, cardiology, neurology, and geriatrics.
    Keywords:   Alzheimer’s disease ; cardiovascular disease ; prophyromonas gingivalis
    DOI:  https://doi.org/10.36740/WLek/218274
  15. Sociol Health Illn. 2026 May;48(4): e70180
      Personalised medicine was initially heralded as delivering 'the right drug to the right patient at the right time'. Although molecular precision has dominated recent developments, the temporal dimension has remained underexplored. This paper examines how temporal precision is emerging as a defining feature of next-generation precision medicine, driven by algorithmic tools and multiomics data integration. Drawing on qualitative interviews with leading experts in personalised immunotherapy and chronic inflammatory disease (CID) medicine, we identify five ways in which temporal precision is reshaping therapeutic practice: extended prediction, timing, synchronisation, coordination of treatments and feedback effects. We show how personalised cancer vaccines and precision inflammation approaches rely on algorithmic assemblages to anticipate therapy effects, coordinate interventions and dynamically adapt treatment schedules. These innovations highlight a shift from molecular precision to personalisation that incorporates the evolving temporality of both disease and therapy, signalling a new development in precision medicine: Diseases are increasingly treated as dynamic processes, therapies as sequences of timed interventions and patients as embedded in feedback loops between body rhythms, pathology and treatment regimens.
    Keywords:  algorithms; personalisation; precision medicine; prediction; synchronisation; time
    DOI:  https://doi.org/10.1111/1467-9566.70180
  16. ACS Appl Mater Interfaces. 2026 Apr 09.
      Periodontitis is a chronic inflammatory disease driven by oral microbial dysbiosis and dysregulated host immunity, in which Porphyromonas gingivalis (Pg) and its lysine-specific gingipain (Kgp) are key pathogenic factors. Although immune targeting of Kgp holds promise for interrupting disease progression, inefficient transmucosal antigen delivery and limited dendritic cell (DC) activation hinder effective mucosal and humoral immune responses. Here, we report a sublingual mucosal nanovaccine based on tetrahedral framework nucleic acids (tFNAs) for precise DC-directed immunomodulation. The vaccine integrates a DC-targeting aptamer, a Kgp-specific antigenic peptide (KAS1), and Cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODNs) adjuvant within a programmable tFNAs scaffold and is embedded in a biodegradable mixed polyethylene glycol-based (MixPEG) hydrogel to enable spatially controlled assembly and sustained sublingual delivery. Leveraging the intrinsic transmucosal transport capability of tFNAs and the bioadhesive properties of the hydrogel, this system achieves noninvasive sublingual administration and efficient uptake by local DCs, inducing notable Kgp-specific immune responses. In a murine periodontitis model, sublingual immunization enhances salivary IgA production, suppresses Pg colonization, attenuates periodontal inflammation, and mitigates alveolar bone loss, representing a potentially promising strategy for periodontitis.
    Keywords:  Porphyromonas gingivalis; mucosal delivery; nanovaccines; periodontitis; sustained release; tetrahedral framework nucleic acids
    DOI:  https://doi.org/10.1021/acsami.5c25646
  17. Curr Pharm Des. 2026 Mar 18.
       INTRODUCTION: The global rise in antibiotic resistance poses a serious threat to public health by undermining the effectiveness of standard antimicrobial therapies. The rapid rise of multidrug-resistant (MDR) bacterial strains has created an urgent demand for the identification of novel drug targets and the development of innovative therapeutic approaches.
    METHODOLOGY: The methodology for this review was based on an extensive literature search using databases such as PubMed, Google Scholar, Scopus, and Web of Science, covering studies from 1998 to 2025. Articles focusing on novel drug targets, antimicrobial resistance mechanisms, and next-generation therapeutic strategies were screened and selected based on their scientific quality and contribution to the field. Data from clinical trial registries and reputable websites were also incorporated to provide comprehensive insights into emerging approaches against multidrug-resistant bacteria.
    RESULTS: The review identifies several promising approaches for combating MDR pathogens. These include targeting bacterial virulence factors, cell wall synthesis enzymes (Mur ligases, Lipid II, and C55-PP), and proteins that mediate resistance. Additionally, advanced drug delivery systems, such as liposomes, solid lipid nanoparticles, exosomes, and biomimetic carriers, enhance antibiotic bioavailability and site-specific action. Pharmacogenomic approaches further personalize treatment regimens, potentially improving outcomes and reducing the emergence of resistance.
    DISCUSSION: The review highlights that multidrug-resistant bacteria continue to pose a significant threat, necessitating the development of innovative therapeutic approaches. Although novel molecular targets and nanocarrier-based delivery systems offer substantial promise, their clinical translation is limited by challenges such as off-target effects, biological barriers to delivery, and regulatory hurdles. Overcoming these obstacles will require the integration of advanced technologies with pharmacogenomics and host-targeted therapeutic strategies.
    CONCLUSION: Combating antibiotic resistance requires an integrated approach combining novel drug targets, advanced delivery systems, and tailored therapeutic approaches. Innovations in nanotechnology, immunotherapy, and pharmacogenomics offer viable solutions to this escalating crisis. Strategic interdisciplinary collaboration is critical for developing sustainable antimicrobial treatments and preserving the efficacy of existing antibiotics.
    Keywords:  Antimicrobial resistance; CRISPR-based therapeutics; antimicrobial peptides; multidrug-resistant bacteria; nanocarrier-based drug delivery.; novel drug targets
    DOI:  https://doi.org/10.2174/0113816128406584251028160407
  18. Enzyme Microb Technol. 2026 Apr 05. pii: S0141-0229(26)00053-0. [Epub ahead of print]198 110870
       BACKGROUND: The increasing prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa highlights the urgent need for innovative therapeutics beyond conventional antibiotics.
    METHOD: In this study, two novel lytic bacteriophages, Pseudomonas phage_SW_PA2862_14_24 (N2) and Pseudomonas phage_SW_PA2862_11_24 (N3) of the myovirus morphology, were isolated and comprehensively characterized for activity against P. aeruginosa isolates. Transmission electron microscopy was used to determine morphotypes, while adsorption assays, one-step growth curves, and time-kill assays assessed infection dynamics. Genomic characterization included whole-genome sequencing and bioinformatic analysis for safety profiling and comparative genomics.
    RESULTS: Electron microscopy revealed distinct morphologies: N2 exhibited a contractile tail, and N3 displayed a flexible, non-contractile tail. Adsorption assays showed that N3 achieved rapid host binding (∼95% within 5 min), while N2 demonstrated a higher burst size of 231 PFU/cell. Genomic analysis identified genome sizes of ∼92.8 kb with 202-203 coding sequences, 15 tRNA genes, and a high proportion (∼73%) of hypothetical proteins. Both phages contained complete lytic modules and conserved genes related to replication and DNA metabolism. Comparative analysis demonstrated high genomic homology with established therapeutic phages (SPA01, EPA1, OMKO1). Time-kill assays confirmed dose-dependent bactericidal efficacy, with N2 showing superior and sustained lytic activity at moderate to high MOIs. Importantly, both genomes lacked lysogeny, antimicrobial resistance, and virulence genes.
    CONCLUSION: These novel phages constitute biosafe, genetically defined lytic agents with distinct infection kinetics and potent activity against MDR P. aeruginosa. Their complementary features and favorable genomic profiles support their potential use in precision phage therapy to combat antibiotic-resistant infections.
    Keywords:  Antimicrobial resistance; Bacteriophage; Genome analysis; Good health and well-being; Lytic phage; Pseudomonas aeruginosa
    DOI:  https://doi.org/10.1016/j.enzmictec.2026.110870
  19. Braz J Infect Dis. 2026 Apr 03. pii: S1413-8670(26)01199-2. [Epub ahead of print]30(3): 105809
      T-cell exhaustion, a well-characterized phenomenon, has historically been studied in the context of viral and oncological diseases. However, its relevance to chronic bacterial infections has only recently garnered attention. This review summarizes emerging evidence suggesting that bacterial pathogens can induce immune exhaustion through a variety of mechanisms. Additionally, we explore how bacterial biofilms, immune-privileged niches, and regulatory T-cell expansion contribute to persistent immune dysfunction. The article further examines the consequences of immune exhaustion, including secondary infections, antibiotic resistance, and microbiome dysbiosis, which are often underappreciated aspects of chronic immune impairment. Therapeutic strategies targeting these exhaustion pathways, such as immune checkpoint blockade, metabolic reprogramming, and microbiome modulation, are also discussed. We emphasize the need to consider chronic bacterial infections not as static conditions but as dynamic processes that interact with and suppress the immune system. Thus, understanding the mechanisms behind immune exhaustion highlights the importance of developing therapies that restore immune function, rather than solely relying on traditional antimicrobial treatments.
    Keywords:  Bacterial infections; Immune response; Immunotherapy; Regulatory T-cells; T-cell exhaustion
    DOI:  https://doi.org/10.1016/j.bjid.2026.105809
  20. Cell Rep. 2026 Apr 08. pii: S2211-1247(26)00297-4. [Epub ahead of print]45(4): 117219
      Chimallivirus bacteriophages enclose their replicating genomes in a protein-based compartment termed the phage nucleus. While the phage nucleus segregates phage DNA from host immune proteins, it is not known if additional factors are required to protect against DNA-targeting host defenses. Here, we identify a chimallivirus-encoded DarG2-like antitoxin that localizes to the phage nucleus and provides protection against phage-targeting DarTG2 toxin-antitoxin systems. This protein, which we term AdfM (anti-darT factor macro), contains a macrodomain and removes DarT2-mediated ADP-ribose modifications from DNA. In the absence of AdfM, DarT2 modifies phage DNA and restricts chimallivirus replication despite being largely excluded from the phage nucleus. Increasing the nuclear concentration of DarT2 while decreasing the nuclear concentration of AdfM reduces phage replication. These results show that the phage nucleus is insufficient to completely protect the chimallivirus genome from host defenses; rather, it is one component of a multilayered counter-defense strategy.
    Keywords:  CP: microbiology; CRISPR; DarT; PhiKZ; jumbo phage; phage defense system; phage nucleus
    DOI:  https://doi.org/10.1016/j.celrep.2026.117219
  21. Pediatr Pulmonol. 2026 Apr;61(4): e71612
       BACKGROUND: People with cystic fibrosis (PwCF) face considerable burden from medical expenses, medications, and daily living with a chronic disease. PwCF want to discuss financial challenges with their care team, although little is known about cystic fibrosis (CF) clinicians discussion practices. We described the current practices and perspectives of CF clinicians regarding cost and financial discussions.
    METHODS: We administered a national, cross-sectional, online survey to CF clinicians through CF Foundation listservs.
    RESULTS: 192 respondents completed the survey and represented all multidisciplinary team members such as licensed practitioners, social workers, nurses, pharmacists, and other involved disciplines. Most respondents (80%) believed CF clinicians should discuss costs of medical care although less than half felt comfortable discussing cost. Social workers were more likely than licensed prescribers to discuss costs and feel comfortable with discussions. 52% of respondents reported having at least one conversation about the annual cost of CF medical care and 73% discussed out-of-pocket costs in the last year. Social workers were identified as the clinician that should be primarily responsible for discussing financial matters. Lack of time during visits (77%), lack of knowledge about topics (74%), and lack of clinician comfort (64%) were the most commonly identified barriers to discussions.
    CONCLUSIONS: Most CF clinicians believe that cost and financial discussions are important and reported engaging in these conversations with patients at least annually. Differences in comfort level and discussion practices were observed between social workers and licensed prescribers. Results demonstrate the opportunity for educational interventions to address clinician knowledge and improve comfort level with discussions.
    Keywords:  cost; cost conversation; cystic fibrosis; financial toxicity; health insurance
    DOI:  https://doi.org/10.1002/ppul.71612
  22. ACS Appl Bio Mater. 2026 Apr 09.
      Damage to the skin barrier renders wounds susceptible to bacterial invasion, resulting in a heightened risk of infection and delayed tissue repair. With advances in materials science and biomedical engineering, antimicrobial hydrogels have emerged as promising dressing candidates for the management of both acute and chronic wounds. Owing to their high water content, excellent biocompatibility, and tunable mechanical and chemical properties, these hydrogels create a moist wound environment, facilitate cell migration, and enable localized antimicrobial regulation. In recent years, the antimicrobial efficacy, tissue-repair capacity, and multifunctionality of hydrogels have been substantially enhanced through the incorporation of inorganic nano-antimicrobial agents, the loading of therapeutic drugs or antimicrobial peptides, and the design of polymer networks with intrinsic bactericidal activity. This review systematically summarizes the main categories, construction strategies, and bactericidal mechanisms of antimicrobial hydrogels, with particular emphasis on their key performance features and advantages in wound healing, as well as an analysis of current challenges in their development. Finally, we provide an outlook on future research directions, including intelligent responsiveness, long-term antimicrobial functionality, personalized therapeutic strategies, and clinical translation. Overall, this review aims to offer insight and guidance for the advancement of efficient and safe antimicrobial hydrogel dressings.
    Keywords:  antibacterial mechanism; application; hydrogels; preparation methods; wound dressings
    DOI:  https://doi.org/10.1021/acsabm.6c00128
  23. Mater Today Bio. 2026 Jun;38 103042
      Methicillin-resistant Staphylococcus aureus (MRSA) infections lead to slow wound healing, but treating these wounds with conventional photodynamic therapy (PDT) remains challenging because they induce non-specific oxidative damage on healthy tissue, thereby hindering wound repair. To achieve efficient antibacterial activity while avoiding non-specific tissue injury, we constructed a DNA aptamer functionalized upconversion nanoplatform (UC@PEI-RB@Apt) for spatially confined, proximity-dependent antibacterial of MRSA. Here, upconversion nanoparticles (UCs) convert near-infrared (NIR) light into visible light, activating polyethyleneimine-modified Rose Bengal (RB) to generate ROS. Crucially, the modified aptamers act as a specific molecular anchor, enabling the nanoplatform to directly adsorb onto the bacterial surface. This generates a proximity-dependent killing effect, wherein lethal ROS are generated around the bacteria to eliminate them, while sparing surrounding healthy cells due to the short lifespan of ROS. In vitro, UC@PEI-RB@Apt exhibited excellent targeting and biofilm disruption ability, with 99.9% bactericidal efficiency. In vivo, the MRSA infected wound model confirmed that this localized treatment significantly reduced bacterial load and accelerated wound closure compared to non-targeted controls. Additionally, histological analysis confirmed excellent biosafety with negligible damage to normal skin or major organs. This study proposes a precise, aptamer-guided targeted strategy that effectively balances high bactericidal activity with tissue safety for managing drug-resistant infections.
    Keywords:  Antibiotic resistance; Antimicrobial photodynamic therapy; Bacteria-targeting aptamer; Biofilm; MRSA; Upconversion nanoparticles
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103042
  24. Bioinformation. 2026 ;22(1): 369-372
      Artificial intelligence (AI) is emerging as a transformative force in periodontal care, reshaping traditional diagnostic, preventive and therapeutic paradigms. Recent advances in algorithms, computational power and access to large-scale digital datasets have enabled the development of sophisticated AI and machine learning (ML) models capable of analyzing complex clinical, radiographic and biological data. These technologies support clinicians in early diagnosis, risk assessment, personalized treatment planning and prediction of disease progression. By integrating AI-driven analytics with the principles of evidence-based dentistry (EBD), periodontal care is transitioning toward more precise, efficient and patient-centered approaches. Thus, we show the evolution of AI in periodontology, its current and emerging clinical applications and its potential to enhance decision-making, optimize outcomes and redefine the future landscape of periodontal practice.
    Keywords:  Artificial intelligence (AI); dental care; electronic brain; machine learning; neural network
    DOI:  https://doi.org/10.6026/973206300220369
  25. Bioinformation. 2026 ;22(1): 392-396
      Obesity and periodontal diseases are highly prevalent chronic conditions linked by shared inflammatory and metabolic pathways. Obesity-induced systemic inflammation, adipokines imbalance and oxidative stress can exacerbate periodontal breakdown, while epidemiological evidence demonstrates a consistent association between excess adiposity and increased periodontitis risk. Understanding these mechanisms supports integrated management strategies combining periodontal therapy with lifestyle and metabolic interventions. This review summarises current biological, epidemiological and clinical evidence on the obesity-periodontitis relationship.
    Keywords:  Obesity; adipokines; inflammation; metabolic syndrome; periodontitis
    DOI:  https://doi.org/10.6026/973206300220392
  26. Wound Repair Regen. 2026 Mar-Apr;34(2):34(2): e70147
      Monofilament fibre pads may offer an effective, less invasive method for managing biofilms in pressure injuries, but their clinical effectiveness in reducing bacteria and biofilms has not been fully evaluated. Although biofilm removal is recommended for wound management, less invasive methods applicable to daily care remain limited. Therefore, this study aimed to assess the effectiveness of monofilament fibre pads compared to gauze in reducing bacterial counts and biofilm burden in pressure injuries. This retrospective cohort study was conducted at a Japanese university hospital. Bacterial counts were measured before and after cleansing using a rapid bacterial quantification system, and biofilm reduction rates were calculated using a wound blotting technique that enables non-invasive and quantitative evaluation of biofilms across the entire wound bed. Linear mixed-effects models were applied to evaluate the association between cleansing materials and outcomes, adjusting for baseline bacterial counts or biofilm brightness and the DESIGN-R2020 total score. Thirty-four pressure injuries in 30 patients were analysed, with 27 wound cleansing procedures performed using gauze and 73 using fibre pads. Fibre pad use significantly reduced bacterial counts (β = 0.389, p = 0.011) and biofilm burden (β = 0.642, p = 0.003) compared with gauze. Sensitivity analyses confirmed that these associations were robust, particularly after adjusting for baseline bacterial counts and biofilm brightness. These findings demonstrate that monofilament fibre pads are effective in reducing bacterial counts and biofilm burden in pressure injuries. Their routine use may provide a practical and less invasive adjunct for routine wound cleansing or maintenance biofilm control by facilitating bacterial and biofilm reduction.
    Keywords:  biofilm; debridement; fibre pad; subclinical infection; wound cleansing
    DOI:  https://doi.org/10.1111/wrr.70147
  27. BMC Microbiol. 2026 Apr 09.
      
    Keywords:  Bacteriophages; MDR-APEC; Phage-antibiotic antagonism; Phage-antibiotic synergism; Polypropylene; Polyvinyl chloride; Stainless steel
    DOI:  https://doi.org/10.1186/s12866-026-05018-3
  28. Acta Clin Belg. 2026 Apr 04. 1-17
       OBJECTIVES: Periodontal disease, characterized by subgingival biofilm dysbiosis and Porphyromonas gingivalis (P. gingivalis) colonization, has been increasingly implicated in Alzheimer's disease (AD) pathogenesis. This review systematically delineates the pathophysiological mechanisms underlying the periodontal-AD nexus, highlighting olfactory dysfunction (OD) and salivary gland hypofunction as putative prodromal biomarkers for periodontal disease-associated AD progression.
    METHODS: PubMed/MEDLINE database was systematically searched for English-language articles published between January 1994 and March 2025. Search terms encompassed periodontal disease, Porphyromonas gingivalis, Alzheimer's disease, neuroinflammation, olfactory dysfunction, salivary gland hypofunction, blood-brain barrier, microglial activation, and cognitive decline.
    RESULTS: Periodontal disease compromises blood-brain barrier integrity via bacterial translocation, systemic pro-inflammatory mediator dissemination, and peripheral immune cell activation, thereby potentiating microglial polarization and neuroinflammatory cascades integral to early AD neuropathology. Both OD and salivary gland hypofunction demonstrate robust associations with periodontal disease severity and constitute sensitive biomarkers for prodromal AD.
    CONCLUSIONS: Periodontal disease-mediated neuroinflammation constitutes a pivotal mechanistic pathway linking oral dysbiosis to AD onset. OD and salivary gland hypofunction emerge as promising early diagnostic indicators for periodontal disease-associated AD susceptibility, warranting prospective clinical validation.
    Keywords:  Alzheimer’s disease; Periodontal disease; neuroinflammation; olfactory dysfunction; salivary gland hypofunction
    DOI:  https://doi.org/10.1080/17843286.2026.2652268
  29. Diabetes Res Clin Pract. 2026 Apr 08. pii: S0168-8227(26)00174-9. [Epub ahead of print] 113255
      Diabetic foot ulcers (DFUs) are devastating complications of diabetes, defined by impaired healing, high amputation rates, and substantial mortality, with pathogenesis rooted in interconnected metabolic, immune, and vascular dysregulation. Serum metabolomic profiling identifies elevated branched-chain amino acid (BCAA) levels in DFU patients, yet the metabolic mechanisms linking BCAA dysregulation to DFU remain unexplored. This review systematically presents a causal framework: impairment of the BCAA metabolic process (downregulation of BCKDH in skeletal muscle/fat tissue), dysbiosis of the intestinal microbiota leading to systemic accumulation of BCAA, and subsequent activation of the mTORC1/NF-κB signaling cascade. This triggers insulin resistance, mitochondrial dysfunction, and oxidative stress, causing macrophages to polarize to the pro-inflammatory M1 phenotype, disrupting the functions of NK cells and neutrophils, and inhibiting angiogenesis mediated by HIF-1α/VEGF forming a self-perpetuating metabolic-immune-vascular vicious cycle, thereby delaying the wound healing process. This review aims to provide a metabolism-centered framework for understanding the pathogenesis of DFU and for informing future diagnostic and therapeutic research.
    Keywords:  Branched chain amino acid; Diabetic foot ulcer; Immune disorder; Inflammation; Metabolic disorder
    DOI:  https://doi.org/10.1016/j.diabres.2026.113255
  30. J Hazard Mater. 2026 Mar 30. pii: S0304-3894(26)00914-3. [Epub ahead of print]508 141936
      The global spread of antibiotic resistant bacteria (ARB), particularly plasmid-bearing strains, poses a major threat to public health due to their association with life-threatening infections. As alternatives to conventional antibiotics become increasingly necessary, bacteriophages are recognized as promising tools for controlling ARB. This study recovered three lytic phages, vB_EcoP_LHP, vB_EcoP_IUE, and vB_EcoM_BL from agricultural soil, which specifically target Escherichia coli K12 carrying the multidrug-resistant plasmid RP4. Based on morphological and phylogenetic analyses, phage LHP was classified within the genus Cronosvirus, subfamily Melnykvirinae, phage BL within the species Felixounavirus JLBYU32, genus Felixounavirus, subfamily Ounavirinae, while phage IUE was identified as a novel Caudoviricetes phage. No virulence, antibiotic resistance, or lysogeny-associated genes were detected, supporting their biosafety for application. Phages LHP and IUE exhibited strong lytic activity against E. coli strains carrying RP4 and pKJK5, with optimal multiplicity of infection of 100 and estimated burst sizes of 40 and 600 PFU/cell, respectively, but were more sensitive to high temperatures. In contrast, phage BL displayed a broader host range, an estimated burst size of approximately 45 PFU/cell, and higher thermal stability. In soil microcosms, substantial reductions in E. coli K12 (RP4) and plasmid persistence were achieved through phage treatment, with the cocktail showing the most rapid and sustained suppression. Notably, durable inhibition was conferred by the phage IUE, whereas moderate effects were exerted by phages LHP and BL. Collectively, these findings highlight the potential of strictly lytic putative plasmid-dependent phages, particularly in cocktails, as eco-friendly biocontrol agents for constraining the environmental dissemination of plasmid-mediated antibiotic resistance. SYNOPSIS: This study isolated and characterized three novel lytic phages and demonstrated their potential, individually and in cocktails, to control soil-borne antibiotic resistant bacteria and plasmid-mediated resistance.
    Keywords:  Antibiotic resistance genes (ARGs); Antibiotic resistant bacteria (ARB); Bacteriophages; Biocontrol; Plasmid-dependent phages (PDPs)
    DOI:  https://doi.org/10.1016/j.jhazmat.2026.141936
  31. J Indian Soc Periodontol. 2025 Nov-Dec;29(6):29(6): 669-672
       Background: Antibiotic resistance poses a major challenge in the control of bacterial infections, including chronic periodontitis. This study aimed to evaluate the antibiotic resistance of Porphyromonas gingivalis to commonly prescribed antibiotics, amoxicillin, amoxicillin-clavulanic acid, and metronidazole, in gingival crevicular fluid (GCF) samples obtained from patients with chronic periodontitis, with and without prior antibiotic exposure.
    Materials and Methods: This study included 24 patients diagnosed with chronic periodontitis, divided into two groups: Group 1 comprised 12 patients with a history of antibiotic exposure within the preceding 6 months and Group 2 comprised 12 patients without any prior antibiotic exposure. GCF samples were collected using sterile absorbent paper points and cultured under anaerobic conditions for the isolation of P. gingivalis. Antibiotic sensitivity was assessed by measuring the zone of inhibition (ZOI) on nutrient agar plates. The data were analyzed using the Mann-Whitney U-test, and statistical significance was set at P < 0.05.
    Results: Patients without prior antibiotic exposure demonstrated a slightly higher mean ZOI (17.66 mm) compared to patients with prior antibiotic exposure (16.66 mm), suggesting marginally better antibiotic effectiveness in the former group. However, this difference was not statistically significant (P = 0.663).
    Conclusion: The findings indicate a reduced antibiotic effectiveness in patients with previous antibiotic exposure. These results underscore the importance of avoiding empirical antibiotic use and support the consideration of narrow-spectrum antibiotics or alternative treatment approaches, such as local drug delivery systems, to mitigate the development of antibiotic resistance.
    Keywords:  Antibiotic resistance; Porphyromonas gingivalis; antibiotics; chronic periodontitis
    DOI:  https://doi.org/10.4103/jisp.jisp_485_24
  32. Cell Host Microbe. 2026 Apr 08. pii: S1931-3128(26)00123-X. [Epub ahead of print]34(4): 567-587
      Microbiome-based interventions for female urogenital health have gained attention, particularly in strategies aimed at restoring lactobacilli dominance to reduce infection and improve reproductive outcomes. These approaches include defined probiotic strains, engineered microbial consortia, and vaginal microbiota transfer. Observational studies have provided ecological insights into the composition and dynamics of the vaginal microbiome; its associations with infections, inflammation, and reproductive complications; and its interplay with urinary and mucosal niches. These data establish a correlative framework linking microbial community structure to health and disease. However, the efficacy of current interventions remains constrained by an incomplete mechanistic understanding of host-microbiome and microbe-microbe interactions. Recent discoveries highlight the role of vaginally derived microbial molecules in modulating host immune responses, stabilizing microbial communities, and influencing disease outcomes. These mechanistic insights provide a basis for the rational design of microbiome-based therapies. This review synthesizes clinical, observational, and mechanistic evidence and outlines research priorities for translation into clinical practice.
    Keywords:  female reproductive tract; live biotherapeutic products; probiotics; urogenital tract; vaginal microbiome
    DOI:  https://doi.org/10.1016/j.chom.2026.03.015
  33. Microb Pathog. 2026 Apr 02. pii: S0882-4010(26)00207-X. [Epub ahead of print]215 108481
      Bacteriophages are ubiquitous bacterial viruses that specifically infect and lyse host bacteria. They display remarkable diversity in environments ranging from wastewater to the deep sea. Despite their widespread occurrence, many aspects of phage biology and their roles in nature remain poorly understood. In particular, phages that infect Pseudomonas aeruginosa (P. aeruginosa) are especially interesting because of their unique biological features related to host lytic capabilities. Only a limited number of P. aeruginosa phages had been documented in the NCBI database. In this study, we isolated a novel phage (P. aeruginosa phage ϕPAE8) from sewage, which demonstrated effective lytic activity against clinically derived antibiotic-resistant P. aeruginosa strains. ϕPAE8 exhibits advantageous physiological traits, including an extended latent period, a high burst size, and notable stability under various stress conditions such as extreme pH, ethanol exposure, and elevated temperature. These characteristics support its potential use in clinical and environmental applications. Therefore, this study also explored the efficacy of bacteriophage ϕPAE8 in controlling multidrug-resistant P. aeruginosa in a sewage environment. All phage-treated groups showed a significant reduction in the number of P. aeruginosa. The most pronounced effect was observed in the treatment group with an MOI of 50. In this group, the bacterial count decreased significantly and rapidly by approximately 3 log10 CFU/mL within 6 h. Even more surprisingly, we found that the impact of different MOIs on the bactericidal effect may have gradually approximated over time. The results highlight the potential of phage-based approaches as an effective strategy for managing antibiotic-resistant bacteria in complex wastewater systems and provide guidance for subsequent practical applications. In summary, this study details the molecular and genomic characteristics of a novel P. aeruginosa phage, contributing to the understanding of viral diversity. More importantly, it underscores the viability of phage-mediated biocontrol in wastewater management. In contrast to chemical disinfectants that may cause secondary pollution, phage-based strategies provide an environmentally friendly approach. These findings establish a conceptual framework to guide future phage bioengineering efforts aimed at combating antimicrobial-resistant pathogens, facilitating their use in medical and water purification settings.
    Keywords:  Bacteriophage; Genomic analysis; Phylogenetic analysis; Pseudomonas aeruginosa; Wastewater treatment
    DOI:  https://doi.org/10.1016/j.micpath.2026.108481
  34. Compend Contin Educ Dent. 2026 Apr;47(3): 110-120
      Misclassification of halitosis frequently results in ineffective treatment. A clinical classification system is presented that organizes halitosis into eight types based on etiology and clinical presentation. Intraoral causes include tongue biofilm, periodontal disease, peri-implant disease, and xerostomia-associated halitosis, while extraoral causes comprise airway related conditions and metabolic/systemic disorders with pulmonary elimination of bloodborne compounds. Perceptual conditions are categorized as pseudohalitosis and halitophobia. A diagnostic workflow is proposed to guide clinicians in distinguishing etiologies.
  35. Microbiol Res. 2026 Apr 01. pii: S0944-5013(26)00075-3. [Epub ahead of print]309 128511
      Inflammatory bowel disease (IBD) care now relies on an expanding portfolio of biologics and small molecules, yet symptom-driven phenotyping often misses molecular endotypes, contributing to primary non-response and loss of response. This review examines how gut microbiota-centered multi-omics can be translated into decision support within treat-to-target (T2T) management and therapeutic drug monitoring (TDM). We synthesize evidence from stool and mucosal metagenomics/metatranscriptomics, virome and bacteriophage signals, metabolomics, blood proteomics, and host transcriptomic/epigenomic and genetic layers, emphasizing analytical validity, external validation, calibration, and action-linked thresholds. Longitudinal data indicate that IBD-associated dysbiosis is predominantly functional and time-varying, enabling applications in diagnosis, prognosis, therapy-response prediction, and monitoring of inflammatory burden and remission depth. However, many reported predictors show limited transportability due to pre-analytical variation, batch effects, endpoint heterogeneity, and confounding by diet, antibiotics, and prior therapies. We propose a pragmatic, tiered workflow: deploy minimal, interpretable signatures at baseline and early induction, and interpret outputs alongside fecal calprotectin/CRP, endoscopy or imaging when indicated, and drug exposure/anti-drug antibodies to distinguish underexposure and immunogenicity from true mechanistic non-response, guiding dose optimization versus mechanism switching. Digital/remote monitoring can operationalize iterative reassessment while reserving deeper omics for decision-critical checkpoints. Overall, the microbiome is best framed as an actionable layer within a multi-signal IBD management system rather than a standalone biomarker; translation will depend on standardization, workflow integration, prospective validation, and demonstrated clinical and economic value.
    Keywords:  Gut microbiota; IBD; Multi-omics; Precision medicine; Therapeutic drug monitoring; Treat-to-target
    DOI:  https://doi.org/10.1016/j.micres.2026.128511