bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–03–22
38 papers selected by
Luca Bolliger, lxBio



  1. Front Microbiomes. 2024 ;3 1450523
      The symbiotic relationship between the gut microbiome and the human body is a concept that has grown in popularity in recent years. Bacteriophages (phages) are components of the gut microbiota and their imbalance plays a role in the pathogenesis of numerous intestinal disorders. Meanwhile, as a new antimicrobial agent, phage therapy (PT) offers unique advantages when compared with antibiotics and brings a new dawn for treatment of multidrug-resistant bacteria in intestinal and extraintestinal disorders. In this review, we provide a brief introduction to the characterization of phages, particularly focusing on newly discovered phages. Additionally, we outline the involvement of gut phages in disease pathogenesis and discuss the status and challenges of utilizing phages as therapeutic targets for treatment of enteric infection.
    Keywords:  bacteriophages; gut microbiome; phage therapy; phage-related diseases; phage–bacteria interaction
    DOI:  https://doi.org/10.3389/frmbi.2024.1450523
  2. Sichuan Da Xue Xue Bao Yi Xue Ban. 2026 Jan 20. 57(1): 250-261
      The growing threat of antimicrobial resistance requires the urgent development of new therapeutic strategies and agents. Bacteriophage therapy offers a promising alternative, utilizing phages' ability to specifically recognize and lyse bacterial cells. The ubiquity of bacteriophages subjects bacteria to constant evolutionary pressure, driving the emergence of diverse systems that defend against phage infection. The repertoire of phage defense genes includes a wide range of functions, such as nucleases, helicases, and ATPases. Host-phage interactions are complex and multifaceted. Bacterial defense mechanisms operate at various levels: initial innate defenses that inhibit phage adsorption, block nucleic acid injection, and interfere with virion assembly; early vesicle rupture targeting phage nucleic acids; systems that specifically target phage DNA and RNA; and abortive infection, which results in the degradation of bacterial nucleic acids, depletion of NAD+, and changes in cell membrane integrity. Notably, abortive infection prevents phage propagation, though at the cost of bacterial cell death. Although many defense systems have been predicted and identified through bioinformatics, the precise molecular mechanisms and detailed pathways of most systems remain poorly understood. Future research should focus on clarifying the exact molecular mechanisms, regulatory networks, distribution patterns, and roles in bacterial fitness for both newly discovered and established defense systems. Such insights are essential for developing innovative strategies to combat bacterial infections. This review examines the core mechanisms and application potential of bacterial antiphage defense. It systematically summarizes four key aspects of the bacterial antiphage defense system: early infection defense, phage nucleic acid-targeted defense, abortive infection defense, and transferable defense strategies. It also highlights current bottlenecks in the field, such as unclear defense mechanisms, insufficient clinical transformation technologies, and risks associated with the transferability of defense systems. Corresponding countermeasures and suggestions are proposed, including in-depth mechanistic research, construction of defense profiles for pathogenic bacteria, and development of engineered phages and synergistic therapies, to provide references for optimizing phage therapy and innovating bacterial infection treatment, thereby offering new perspectives for treating bacterial infections.
    Keywords:  Abortive infection; Bacteria; Bacteriophages; Defense systems; Infection; Review
    DOI:  https://doi.org/10.12182/20260160205
  3. Trends Mol Med. 2026 Mar 19. pii: S1471-4914(26)00031-6. [Epub ahead of print]
      Bacteriophages (phages) are emerging as programmable biological therapeutics in oncology, extending beyond their traditional antimicrobial applications. This review proposes a phage-microbiome-immune-oncology axis that links microbial dynamics, immune modulation, and engineered phages to guide precision cancer prevention and therapy. Phages can eliminate cancer-associated bacteria, remodel the tumor microenvironment, enhance antitumor immunity, and deliver targeted therapeutic payloads. However, several critical challenges must be addressed to realize this therapeutic potential, particularly host immune responses that limit repeat dosing, inefficient tumor penetration, and the need for rigorous clinical validation. By examining phage-host-tumor interactions through robust model systems and highlighting translational opportunities, this review establishes phage therapy as a promising frontier in precision oncology that warrants accelerated clinical development.
    Keywords:  cancer prevention; immunotherapy; microbiome; phage therapy; precision oncology; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.molmed.2026.02.001
  4. Vet Microbiol. 2026 Mar 10. pii: S0378-1135(26)00119-7. [Epub ahead of print]316 110988
      Bacteriophages (phages) are viruses that infect and may kill bacteria. Phage therapy has gained global attention as a possible means to circumvent problems of bacterial antimicrobial resistance (AMR) in food animal production systems. In preparing this overview on the use of phage therapy in terrestrial food animals, 127 published research articles were analysed to obtain a contemporary background on phage therapy, the efficacy of phage administration, research gaps, and future research directions. Most of the published in vivo trials in chickens described administering phages as biocontrol agents, whereas in vivo trials in pigs administered phages as therapeutics. Only a few trials were conducted in cattle and sheep, targeting foodborne, udder and skin infections. The most common target bacteria in poultry trials were Salmonella Enteritidis, followed by Escherichia coli, Salmonella Typhimurium, Salmonella Pullorum, and Campylobacter jejuni. In contrast, antimicrobial resistant strains of S. Typhimurium and E. coli were the target bacteria in the pig trials. Most studies administered phage cocktails rather than single phage preparation, with bacterial challenge doses varying from 10³ to 10¹⁰ colony forming units (CFU), and phage doses ranging from 10⁵ to 10¹¹ plaque forming units (PFU). In all the reviewed studies phage treatment consistently reduced bacterial load by 0.4-5.0 log₁₀ CFU in feces, meat, and both external and internal organs. Moreover, as a therapeutic, phages were reported to cure diarrhea, improve nutrient digestibility, and enhance weight gain. Phage therapy also reduced specific serum IgG levels against the target bacteria and lowered neutrophil counts and TNF-α concentrations. Together these studies suggest that phage therapy may be an effective treatment approach in controlling certain key infections and hence alleviating bacterial resistance in food animals. Nevertheless, global collaboration and inclusive research on cost-effective production, efficient delivery methods, phage resistance, and host immune responses are essential for overcoming hurdles and facilitating the widespread application of phage therapy in food animals.
    Keywords:  AMR; Bacteriophages; Food animals; In vivo efficacy; Phage therapy
    DOI:  https://doi.org/10.1016/j.vetmic.2026.110988
  5. ASM Case Rep. 2026 Mar;pii: e00108-25. [Epub ahead of print]2(2):
       Background: Bacteriophages (phages), viruses ubiquitous in the environment infecting bacteria, are an increasingly attractive option for adjunct therapy with conventional antibiotics in complicated, refractory multidrug-resistant infections. Bacteria ("hypermutators") with defects in methyl-directed mismatch repair (MMR) have been described in Pseudomonas aeruginosa, with the resultant defect in DNA repair responsible for rapid development of antimicrobial resistance.
    Case Summary: A 72-year-old male with mild chronic obstructive pulmonary disease, diagnosed with resectable, advanced right frontoethmoid adenoid cystic carcinoma, underwent endoscopic resection to remove the affected bone and tissue. The subsequent large craniofacial defect was reconstructed with non-vascularized calvarial bone grafts, rigidly fixated with titanium hardware and externally covered with a vascularized pericranial flap. He developed complete dehiscence of the skull base reconstruction, and wound cultures grew multiple susceptible P. aeruginosa isolates with distinct morphologies that became progressively drug resistant on treatment. Whole-genome sequencing of isolates showed the presence of a non-synonymous mutation in the mutS gene impacting the MMR pathway, consistent with a hypermutator. Phage therapy was pursued due to ongoing infection with retained hardware, lack of clinical response to antibiotic therapy alone, extreme antibiotic resistance, and possible surgical cure of his cancer. He received twice-daily intravenous phage therapy in combination with cefiderocol for 2 weeks with clinical and microbiological resolution of his infection.
    Conclusion: This case suggests that phage therapy may be useful in the treatment of deep-seated hypermutator P. aeruginosa infections with retained hardware.
    Keywords:  Pseudomonas aeruginosa; hypermutator; phage therapy
    DOI:  https://doi.org/10.1128/asmcr.00108-25
  6. Curr Pharm Des. 2026 Mar 12.
      Wound healing is a complex biological process consisting of four key phases: hemostasis, inflammation, proliferation, and remodeling. While acute wounds typically heal without complications, chronic wounds present a major healthcare concern due to persistent infections, poor drug delivery, and delayed tissue regeneration. Nanotechnology has emerged as a promising tool for enhancing wound care by improving drug delivery, reducing microbial load, and supporting tissue repair. This review highlights the application of various nanocarriers, including liposomes, niosomes, hydrogels, and solid lipid nanoparticles, for wound management. These systems enhance drug retention at the wound site, control release profiles, and promote cell proliferation and angiogenesis. Many also exhibit antimicrobial and anti-inflammatory properties, making them suitable for chronic wound treatment. The integration of phytochemical-based compounds into nanosystems is discussed, offering sustainable, biocompatible, and cost-effective approaches. Hybrid platforms, such as nanocomposite hydrogels and bioactive nanoparticles, are presented for their improved healing outcomes and multifunctional performance. Furthermore, the review includes recent patents to reflect technological advancements and innovation in this field. Despite promising developments, challenges such as scalability, cost, and regulatory considerations remain. Future research should focus on improving the design, safety, and accessibility of nanotechnology-based wound therapies.
    Keywords:  Wound healing; chronic wounds; hydrogels; liposomes; nanocarriers; nanotechnology; niosomes; tissue regeneration.
    DOI:  https://doi.org/10.2174/0113816128406511251204074124
  7. Arch Microbiol. 2026 Mar 17. pii: 276. [Epub ahead of print]208(6):
      
    Keywords:  CRISPR-based antimicrobials; antimicrobial peptides; antimicrobial resistance; bacteriophage therapy; multidrug-resistant bacteria; rapid molecular diagnostics
    DOI:  https://doi.org/10.1007/s00203-026-04817-6
  8. Front Cell Infect Microbiol. 2025 ;15 1673512
      The oral-gut axis represents a critical bidirectional pathway linking oral microbiota to systemic health. Dysbiosis of the oral microbiome, driven by pathogens like Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus species, and Helicobacter pylori, disrupts gut ecology via direct translocation, metabolite signaling (e.g., TMAO, SCFAs), and immune crosstalk (e.g., Th17). This leads to gut barrier dysfunction, systemic inflammation, and metabolic disturbances, contributing to diverse diseases beyond the oral cavity. Evidence supports causal links with conditions including rheumatoid arthritis, cardiovascular diseases, neurodegenerative disorders, metabolic syndrome, and gastrointestinal cancers. Emerging diagnostic tools exploit these oral pathogens as biomarkers for non-invasive disease detection. Therapeutic strategies, such as probiotics, dietary interventions, and periodontal therapy, target this axis to restore microbial homeostasis and ameliorate systemic inflammation. Future research must focus on longitudinal human studies and multi-omics approaches to elucidate mechanistic details and develop effective clinical interventions for preventing and managing systemic diseases linked to oral-gut microbial dysbiosis.
    Keywords:  Fusobacterium nucleatum; Porphyromonas gingivalis; Streptococcus mutans; gut microbiota; oral microbiota; systemic disease
    DOI:  https://doi.org/10.3389/fcimb.2025.1673512
  9. J Crit Care. 2026 Mar 19. pii: S0883-9441(26)00097-3. [Epub ahead of print]94 155519
       BACKGROUND: Severe burn injury is associated with profound physiological derangement and remains a major cause of infection-related morbidity and mortality worldwide. Disruption of the skin barrier sustained immune dysregulation, prolonged intensive care unit (ICU) exposure, and extensive use of invasive devices create a uniquely infection-prone host environment. Infectious complications, particularly those caused by multidrug-resistant organisms (MDROs), continue to account for a substantial proportion of deaths in critically ill burn patients despite advances in surgical and critical care management.
    OBJECTIVES: This narrative review aims to provide a comprehensive, clinically focused overview of infectious complications in critically ill burn patients, integrating current evidence on epidemiology, pathophysiology, microbial dynamics, diagnostic strategies, and contemporary management approaches relevant to daily ICU practice.
    SOURCES OF EVIDENCE: A narrative synthesis of the published literature was performed, including international guidelines, observational studies, randomised trials, systematic reviews, and translational research focusing on burn-related infections, antimicrobial resistance, diagnostics, and emerging therapies.
    CONTENT: The review examines the multifactorial pathophysiology underlying infection susceptibility following major burns, including loss of the cutaneous barrier, hyperinflammatory responses followed by immune paralysis, and burn-induced hypermetabolism. Dynamic patterns of microbial colonisation, biofilm formation, microbiome disruption, and the global rise of MDROs are explored. Diagnostic challenges in distinguishing colonisation from invasive infection are discussed, alongside traditional and advanced diagnostic modalities such as quantitative tissue cultures, biomarkers, multiplex molecular assays, and next-generation sequencing. Contemporary management strategies are reviewed, emphasising early surgical source control, pharmacokinetically optimised antimicrobial therapy, antimicrobial stewardship, and rigorous infection prevention and control practices. Emerging adjunctive therapies, including bacteriophage therapy, nanotechnology-based antimicrobials, microbiome-directed interventions, and immunomodulatory approaches, are also highlighted.
    IMPLICATIONS: Effective infection management in burn patients requires an integrated, multidisciplinary approach that combines rapid diagnosis, early surgical intervention, tailored antimicrobial therapy, and robust infection prevention strategies. Advances in molecular diagnostics, precision medicine, and microbiome science hold promise for improving outcomes and mitigating the growing burden of antimicrobial resistance in burn ICUs.
    CONCLUSIONS: Infectious complications remain a leading determinant of outcome following severe burn injury. Optimising infection care through early recognition, precise diagnostics, coordinated surgical and antimicrobial strategies, and emerging precision-based interventions is essential to reduce infection-related morbidity and mortality in this vulnerable patient population.
    Keywords:  Burn injury; Burn wound infection; Critical care; Multidrug-resistant organisms; Surgical source control
    DOI:  https://doi.org/10.1016/j.jcrc.2026.155519
  10. Adv Skin Wound Care. 2026 Apr 01. 39(3): 124-134
      Diabetic foot infections (DFIs) are a serious complication of diabetes, leading to high rates of hospital admission, amputation, and early death-particularly in persons living in resource-limited communities. Although the updated International Working Group on the Diabetic Foot guidelines in 2024 provide well-laid-out strategies for managing DFIs, these tend to be better suited for use in well-resourced centers. This case-based review discusses and applies these guidelines for an approach to DFI in real-world scenarios. It focuses on supporting health care providers working in community and resource-limited settings. The review explores how to recognize and diagnose DFI, including the use of imaging modalities, and how to distinguish soft tissue infection from bone infection or noninfectious entities. Management strategies are detailed regarding antibiotic considerations and approaches, including in resource-limited settings, and when other interventions or surgical referral may be important. Practical clinical cases are used to illustrate key points, emphasizing how care may be adapted based on the context. The authors also consider health equity aspects by identifying barriers that may be faced by patients who are from racialized backgrounds and live in resource-limited settings. The review aims to equip frontline wound clinicians with a pragmatic approach to managing DFIs that is grounded in up-to-date evidence framed in a real-world context.JOURNAL/aswca/04.03/00129334-202604000-00004/figure1/v/2026-03-10T151712Z/r/image-jpeg GENERAL PURPOSE: To provide clinicians with an evidence-based approach to the diagnosis and management of diabetic foot infections (DFIs). TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:Analyze evidence-based clinical and laboratory findings to accurately diagnose (DFIs) and diabetic foot osteomyelitis.Evaluate patient-specific clinical data to select evidence-based management strategies for patients with (DFIs) and diabetic foot osteomyelitis.
    Keywords:  antimicrobials; diabetes; diabetic foot infection; foot ulcer; wound care
    DOI:  https://doi.org/10.1097/ASW.0000000000000422
  11. Curr Res Microb Sci. 2026 ;10 100569
      Avian colibacillosis, caused by avian pathogenic Escherichia coli (APEC), results in high morbidity and mortality and reduces egg production in domestic poultry. Increasing antimicrobial resistance (AMR) and restriction on antibiotic use necessitate alternative disease control strategies. We evaluated the efficacy of a phage cocktail (Tequatrovirus, Sashavirus, and an unclassified Caudoviricetes) at a multiplicity of infection > 100, administered for 4 days in drinking water (DW) or as a single intramuscular (IM) treatment, in preventing experimental APEC infection (108 CFU given intravenously) in specific-pathogen-free laying hens (25-27 weeks old, n=10 per experimental group). Phage treatment reduced mortality from 20% to 0 and morbidity by 30%. Birds receiving phages in DW showed a marginal trend toward reduced weight loss (p = 0.063) than those in IM or APEC-only groups at 4 days post-infection. Macroscopic lesions were present in 6.7-11.7% of organs in APEC-only and IM groups but were absent in DW-treated hens. In the DW group, median histopathological scores were lower, with the most notable reduction (p = 0.006) in the spleen. Across organs, concentrations of recovered phages were similar between DW and IM groups (p = 0.227); however, in the DW group, 1.3-2.1 log10 PFU/g of phages were detected in all tissues except blood. Based on 16S rRNA gene sequencing, neither IM nor DW phage treatments altered the overall general bacterial structure or population in the cecum. We conclude that this phage cocktail, administered via DW, lysed APEC without disrupting gut microbiota, improved overall bird health and welfare, and protected internal organs from APEC invasion.
    Keywords:  Avian colibacillosis; Avian pathogenic E. coli (APEC); Clinical pathology; Drinking water administration; Gut microbiota; Intramuscular delivery; Phage therapy
    DOI:  https://doi.org/10.1016/j.crmicr.2026.100569
  12. Sichuan Da Xue Xue Bao Yi Xue Ban. 2026 Jan 20. 57(1): 37-43
      Oral malodor, a common oral symptom, is primarily caused by the metabolic activities of oral microorganisms. The characteristic odors mainly originate from volatile sulfur compounds produced and released by oral bacteria (such as Fusobacterium nucleatum and Porphyromonas gingivalis) through specific enzymatic systems that break down sulfur-containing amino acids in saliva, gingival crevicular fluid, and food debris. Research indicates that various factors, including periodontitis, fungal infections, smoking, and obesity, can worsen oral malodor by altering the oral microenvironment. For prevention and treatment, novel interventions such as plant extracts, antimicrobial peptides, and probiotics demonstrate superior microbiological safety compared to traditional antimicrobial drugs. These approaches specifically inhibit pathogenic bacteria, disrupt biofilm structures, and regulate oral microbial balance. This review summarizes relevant research advances to provide new theoretical foundations and practical directions for the precise prevention and treatment of oral malodor.
    Keywords:  Dorsal tongue biofilm; Microorganisms; Oral malodor; Periodontal diseases; Review; Volatile sulfur compounds
    DOI:  https://doi.org/10.12182/20260160602
  13. Crit Rev Oncol Hematol. 2026 Mar 18. pii: S1040-8428(26)00169-1. [Epub ahead of print] 105282
      Oral mucositis (OM) is a debilitating toxicity of chemotherapy and radiotherapy that compromises nutrition, quality of life, treatment adherence, and overall cancer outcomes. Despite its clinical impact, therapeutic options remain limited, and our descriptive analysis of the clinical trial landscape reveals about 93.75% attrition rate from clinical success to regulatory approval, highlighting the limitations of single-pathway strategies that target epithelial injury alone. Emerging evidence implicates oral microbiome as an active contributor to OM initiation, inflammatory amplification, and delayed healing, interacting dynamically with host immune responses to shape disease trajectory. These insights support a shift toward multi-targeted therapeutic frameworks that concurrently address epithelial protection, host-immune modulation, and microbial dysbiosis. This approach is increasingly reflected in the growing pipeline shift toward multifunctional compounds and microbiome-based approaches. This suggests that successful OM management will require the integrated antimicrobial and anti-inflammatory approaches, potentially guided by patient-specific microbiome profiling.
    Keywords:  Bacteriome; Candida albicans; Drug development; Dysbiosis; Host-pathogen interactions; Inflammation; Oxidative stress
    DOI:  https://doi.org/10.1016/j.critrevonc.2026.105282
  14. Wound Repair Regen. 2026 Mar-Apr;34(2):34(2): e70133
      Wound healing is a complex process increasingly compromised by aging and comorbidities. Statins are widely used therapeutic agents and have shown promising pleiotropic effects that may enhance wound repair. Our aim is to examine the effects of statins on wound healing in animal models through a quantitative synthesis of preclinical evidence. A systematic review of PubMed, Web of Science and Embase was performed to identify in vivo preclinical experimental studies comparing statin treatment versus vehicle in mammalian animal models of any age or sex with experimentally induced wounds. Multiple independent, blinded reviewers oversaw the study selection, data extraction and quality assessment, following PRISMA (1), SYRCLE (2) and CAMARADES guidelines. Of 220 abstracts screened, 54 full-text articles were assessed for eligibility, and 12 experimental studies published between 2012 and 2026 were included in our meta-analysis. These studies, conducted on mammalian animal models, involved a total of 262 animals and provided 131 comparisons across 14 experiments. Wound closure outcomes were assessed via morphometric analyses between days 9 and 14. Our findings indicate that statin treatment significantly enhances wound size reduction compared to control, with a pooled standardised mean difference (SMD) of 1.79 (95% CI: 0.63-2.95, p = 0.0040). These results provide robust preclinical evidence that statin treatment enhances wound healing in mammalian models. These results support the therapeutic potential of statins in wound care, highlighting the need for further research to elucidate their underlying mechanisms and to facilitate the translation of these preclinical insights into clinical practice.
    Keywords:  HMG‐CoA reductase inhibitors; animal models; preclinical studies; statins; wound closure; wound healing
    DOI:  https://doi.org/10.1111/wrr.70133
  15. J Vis Exp. 2026 Feb 27.
      The prevalence of diabetic foot ulcers (DFU), one of the most common complications of diabetes mellitus (DM), varies significantly across different countries, but remains high globally. The presence of DFU is associated with escalated healthcare expenditures, compromised physical functioning, and diminished quality of life, with a 5-year mortality rate 2.5 times higher than diabetes patients without foot ulcers. Common therapeutic strategies for DFU include glycemic control, eradication of infections, alleviation of pressure on the ulcers, and facilitation of wound healing. CHM, a fundamental element of Traditional Chinese Medicine, has gained widespread recognition in both oral and topical applications for the management of chronic wounds, owing to its functions of detoxification, promotion of blood circulation, removal of blood stasis, and enhancement of wound healing, as outlined in Chinese Medicine theories. Therefore, it is imperative to conduct a comprehensive literature review on the utilization of topical CHM for treating DFU in order to provide evidence-based guidance for clinical practice.
    DOI:  https://doi.org/10.3791/69239
  16. Front Microbiomes. 2024 ;3 1408203
      Metagenomic studies have revolutionized the study of novel phages. However these studies trade depth of coverage for breadth. We show that the targeted sequencing of a small region of a phage terminase family can provide sufficient sequence diversity to serve as an individual-specific barcode or a "phageprint'', defined as the relative abundance profile of the variants within a terminase family. By collecting ~700 oral samples from ~100 individuals living on multiple continents, we found a consistent trend wherein each individual harbors one or two dominant variants that coexist with numerous low-abundance variants. By tracking phageprints over the span of a month across ten individuals, we observed that phageprints were generally stable, and found instances of concordant temporal fluctuations of variants shared between partners. To quantify these patterns further, we built machine learning models that, with high precision and recall, distinguished individuals even when we eliminated the most abundant variants and further downsampled phageprints to 2% of the remaining variants. Except between partners, phageprints are dissimilar between individuals, and neither country-of-residence, genetics, diet nor cohabitation seem to play a role in the relatedness of phageprints across individuals. By sampling from six different oral sites, we were able to study the impact of millimeters to a few centimeters of separation on an individual's phageprint and found that such limited spatial separation results in site-specific phageprints.
    Keywords:  forensics; machine learning; metagenomics; oral microbiome; phages; terminase; virome; virus
    DOI:  https://doi.org/10.3389/frmbi.2024.1408203
  17. Sichuan Da Xue Xue Bao Yi Xue Ban. 2026 Jan 20. 57(1): 1-7
      The microecological theory represents the current understanding of dental caries etiology, emphasizing that the dynamic balance of the structure and function of the oral microbial community plays a central role in the initiation and progression of caries. This theory posits that dental caries is not caused by a single specific pathogen, but rather results from dysbiosis-an imbalance-of the entire oral microecosystem. By redefining caries from an "infectious disease" to an "ecological imbalance disorder," the microecological theory offers a novel perspective for caries prevention, early intervention, and precision treatment. It underscores that maintaining the homeostasis of the oral microecology is more critical than simply eradicating bacteria, and that ecological approaches represent a key strategy for population-level caries prevention. Homeostatic medicine emphasizes that the dynamic equilibrium of the body's internal environment is fundamental to health. As a major microbial habitat and immunological interface, the oral cavity plays a pivotal role in the body's overall homeostatic network. The stability of the oral microbiome is thus a crucial node in systemic homeostasis. Homeostatic medicine provides a systems-oriented framework for understanding dental caries, shifting the paradigm ofcaries management from "fighting pathogens "toward "preserving ecological balance". This integrative approach aims to achieve the broader goal of promoting systemic homeostasis through local oral health promotion.
    Keywords:  Dental caries; Ecological prevention; Homeostatic medicine; Microecological theory; Oral microbiome; Review
    DOI:  https://doi.org/10.12182/20260160301
  18. J Cyst Fibros. 2026 Mar 17. pii: S1569-1993(26)00056-1. [Epub ahead of print]
       INTRODUCTION: Burkholderia cepacia complex (BCC) comprises 25 species known to cause disease primarily in people with cystic fibrosis (pwCF). Isolation of BCC has major implications for infection control, eradication strategies, morbidity, and lung transplant eligibility. Although not considered part of the BCC, other Burkholderia species are known to cause respiratory disease in pwCF, namely Burkholderia gladioli and Burkholderia pseudomallei. The introduction of CFTR modulator therapy has improved pulmonary outcomes in pwCF, yet little is known about their impact on Burkholderia species acquisition, clearance, or long-term microbiological or clinical outcomes.
    METHOD: We reviewed the outcomes of pwCF infected with Burkholderia species (including BCC, B. gladioli, or B. pseudomallei) receiving care in a large CF centre over the past 15 years, spanning the introduction of CFTR modulator therapy.
    RESULTS: Forty-four pwCF cultured one of these organisms between 2010 and 2025. Ten had only a single isolation with 28 (63.6%) deemed to have chronic infection and 6 (13.6%) exhibiting transient infection defined by having only two positive cultures. Notably, no new Burkholderia species acquisitions occurred after commencement of elexacaftor/tezacaftor/ivacaftor (ETI). The longitudinal incidence rates of chronic infection with Burkholderia species showed a reducing trend from 2017-2025 with rates of spontaneous clearance following ETI appearing similar to background clearance rates prior to modulator therapy.
    CONCLUSION: These findings contribute to the evolving understanding of Burkholderia species in the modulator era. While ETI does not eliminate the risk of chronic infection, it may reduce acquisition and support clearance in a subset of pwCF.
    Keywords:  Burkholderia cepacia; CFTR modulators; Cystic Fibrosis; Elexacaftor/tezacaftor/ivacaftor
    DOI:  https://doi.org/10.1016/j.jcf.2026.03.011
  19. Arch Microbiol. 2026 Mar 17. pii: 269. [Epub ahead of print]208(6):
      
    Keywords:  Artificial intelligence; Bacteriophage; Host range; Protein engineering; Receptor-binding protein
    DOI:  https://doi.org/10.1007/s00203-026-04830-9
  20. Front Microbiomes. 2025 ;4 1553243
      Autoimmune diseases arise from the immune system's dysregulated attack on the body's own tissues, influenced by a complex interplay of genetics, environment, and the microbiome. This comprehensive review and meta-analysis examines the dynamic relationship between gut microbiota and autoimmune diseases, highlighting their role in disease onset, progression, and potential therapeutic interventions. Emerging evidence underscores the bidirectional interactions between microbiota and immune pathways, particularly through mechanisms like mucosal immune modulation and regulatory T-cell activity. Microbiota dysbiosis, characterized by altered diversity and function, is consistently associated with autoimmune conditions such as rheumatoid arthritis, multiple sclerosis, and type 1 diabetes. The review identifies critical microbiota-driven factors, including antigenic mimicry and inflammatory signaling pathways that disrupt immune tolerance and exacerbate autoimmunity. Meta-analysis findings reveal a consistent reduction in microbial diversity across autoimmune diseases, emphasizing the role of specific taxa and their metabolites in influencing disease severity and immune responses. Therapeutic strategies, such as probiotics, prebiotics, and microbiome-targeted interventions, offer promising avenues to restore microbiome balance and mitigate autoimmune inflammation. Despite significant advances, challenges in methodology, limited longitudinal studies, and heterogeneity in results highlight the need for standardized research protocols and larger, well-controlled clinical trials. Future studies should prioritize personalized approaches to microbiome modulation, integrating dietary, genetic, and environmental factors to improve disease management and prevention. This work consolidates current knowledge, providing a framework for future research and clinical applications in the field of microbiome-autoimmune interactions.
    Keywords:  autoimmune diseases; dysbiosis; gut microbiome; immune regulation; microbiome-targeted therapy
    DOI:  https://doi.org/10.3389/frmbi.2025.1553243
  21. Infect Prev Pract. 2026 Jun;8(2): 100522
      Antimicrobial resistance (AMR) is a major global health challenge that threatens the effective prevention and treatment of infections. It arises from increasing resistance rates, limited diagnostic capacity, inappropriate antimicrobial use, and a declining pipeline of new antibiotics. These challenges highlight the need for innovative approaches to complement existing AMR control strategies. Artificial intelligence (AI) has emerged as a valuable tool to address the complexity and scale of AMR. This narrative review examines how AI can be more effectively integrated into key components of AMR management. By analysing large clinical and laboratory datasets, AI-based surveillance and predictive models enable near real-time monitoring of resistance patterns and early outbreak detection. AI-powered diagnostic tools, including image analysis and genomic methods, improve rapid pathogen identification and prediction of antimicrobial susceptibility. In clinical practice, AI-driven decision support systems strengthen antimicrobial stewardship by optimizing prescribing and monitoring antibiotic use. In addition, deep learning approaches accelerate antimicrobial drug discovery and repurposing, reducing development timelines. AI also enhances the detection and surveillance of resistance genes through genomic and metagenomic analyses across human, animal, and environmental settings. Despite its potential, AI applications in AMR face challenges related to data quality, bias, interoperability, privacy, and clinician adoption. Therefore, AI should be seen as a tool that supports, rather than replaces, existing AMR strategies. When regulated well and integrated within One Health frameworks, AI can strengthen surveillance, improve treatment decisions, and support evidence-based interventions to curb AMR.
    Keywords:  Antimicrobial resistance; Artificial intelligence; Challenges; Opportunities
    DOI:  https://doi.org/10.1016/j.infpip.2026.100522
  22. Front Antibiot. 2026 ;5 1768331
      The continuous use of antibiotics has led to the development of antibiotic resistance among bacterial pathogens, posing a significant threat to both human and animal health. This necessitates exploring alternative solutions to combat this growing resistance. Natural products offer a viable alternative for microbial modulation, exhibiting diverse antibacterial processes and the capacity to modify microbial communities and biofilms. These compounds show potential as supplementary agents against resistant infections. Natural products derived from microbes are utilized as biofertilizers and biopesticides, enhancing crop yield and controlling plant pathogens, thereby offering an eco-friendly alternative to chemical fertilizers. Antimicrobial peptides (AMPs) are crucial for combating fish-associated pathogens, reducing mortality rates in the aquaculture industry. Various bacteriocins, are used as food preservatives to inhibit spoilage and pathogenic microorganisms proving their potential in the food industry. In this review, the potential role of natural products from microbes in the food, agriculture, and aquaculture industry sectors has been elucidated. The challenges and prospects were also discussed to provide a foundation for identifying new research opportunities.
    Keywords:  antibiotics; antibiotics resistance; antimicrobial peptides; bacteriocins; microbial modulation
    DOI:  https://doi.org/10.3389/frabi.2026.1768331
  23. Curr Pharm Des. 2026 Mar 12.
      This study provides a comprehensive overview of nanomicelle-based drug delivery methods used to treat ocular disorders. A review of current literature was conducted by scanning electronic databases up until December 2024, including PubMed, Scopus, Web of Science, and Google Scholar. Keywords such as "Nanomicelles" and specific ocular conditions including "Glaucoma," "Conjunctivitis," "Cataract," and "Retinopathy" were used to identify relevant material. Original research articles, reviews, and clinical trials were given special attention. Administering drugs to the eye remains one of the most challenging tasks among various drug delivery systems. Delivering drugs to the posterior pole or the delicate anatomical layers of the eye poses a substantial challenge for researchers and pharmacologists. Conventional formulations often exhibit inadequate corneal penetration, poor absorption, or noticeable adverse visual effects. Nanotechnology has greatly facilitated the development of novel therapeutic strategies for ocular disorders. Nanomicelle-based formulations benefit significantly from the nano-delivery platform. Nanomicelles can overcome anatomical barriers and clearance processes. Depending on the polymer used, nanomicelles can be engineered and released to meet specific requirements. They are notable for their small size, low toxicity, ability to improve drug penetration through ocular epithelia with minimal irritation, enhancement of hydrophobic drug solubility, achievement of therapeutic concentrations, and prevention or reduction of drug degradation. This study highlights the use of nanomicellar-based delivery systems in treating ocular diseases such as diabetic retinopathy, glaucoma, age-related macular degeneration, cataract, conjunctivitis, keratitis, and retinoblastoma.
    Keywords:  Ocular; cornea; degeneration; eye; glaucoma.; micelles
    DOI:  https://doi.org/10.2174/0113816128416157251203061416
  24. Pharmacotherapy. 2026 Apr;46(4): e70138
      The advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators has dramatically changed the landscape of the clinical care of people with cystic fibrosis (PwCF). In particular, highly effective modulator therapy (HEMT) availability for the majority of PwCF has led to changes in pharmacotherapy regimens and clinical outcomes but has also been associated with adverse effects and drug interactions. The role of CFTR modulator therapy perinatally continues to be of great interest, related to both the mother with CF as well as the infant in utero and after birth. As the median life expectancy for PwCF continues to increase, consideration must also be given for treatment of cardiovascular disease and other comorbidities as well as cancer screening and other preventative care measures.
    Keywords:  cystic fibrosis; cystic fibrosis transmembrane conductance regulator; pulmonology
    DOI:  https://doi.org/10.1002/phar.70138
  25. Nat Commun. 2026 Mar 20.
      Viral sequences in diverse environments remain largely uncharacterized, impeding our comprehension of their genetic makeup, biological interactions, and potential applications. This underscores an urgent need for innovative analytical methods. Here, we present the VirHost Hunter framework, which employs phage tails and lysins, bypassing the requirement for full genomes, for efficient and high-resolution host assignment. By harnessing Protein Language Models and Vision Transformers, VirHost Hunter captures protein functional homology despite sequence dissimilarity, significantly boosting prediction accuracy. In the scenario of disease-associated gut bacteria, the calibrated VirHost Hunter surpasses existing methods, doubling phage host assignments, expanding taxonomic reach, and revealing previously uncharacterized phages targeting gut bacteria, including Akkermansia and Prevotella. Therefore, we establish a gut phage lysin database, enabling the synthesis of a lysin that effectively and specifically targets an obesity-promoting bacterium. VirHost Hunter's precision and scalability mark a significant leap forward in virome research and present a promising avenue for microbiome therapies.
    DOI:  https://doi.org/10.1038/s41467-026-70613-x
  26. Probiotics Antimicrob Proteins. 2026 Mar 17.
      Gut microbiota resilience, the capacity of intestinal microbial communities to resist, adapt, and recover from perturbations has emerged as a critical determinant of human health and longevity. Environmental stressors such as antibiotics, pollutants, poor diet, infections, and psychosocial stress challenge this resilience, often leading to dysbiosis (a sustained disruption of microbial community structure and/or function), impaired metabolism, chronic inflammation, and increased disease susceptibility across the lifespan. While dysbiosis has been extensively studied, the resilience dimension remains underexplored, particularly in the context of cumulative and repeated stress exposures. This narrative review explores microbial resilience, identifying environmental disruptors, and their manifestation at life stages, highlighting its hidden yet crucial role in optimizing lifespan. We critically evaluate the consequences of reduced resilience for chronic disease, frailty, and therapeutic response, while emphasizing the protective roles of diversity, functional redundancy, and host-microbe feedback loops. Translational strategies including dietary modulation, microbial therapeutics, behavioral interventions, and precision tools such as multi-omics and biosensors, are assessed for their potential to strengthen resilience and promote healthy aging. By reframing gut microbiota resilience as both a biological property and a public health target, this work advances a novel perspective: that fostering resilience may mitigate environmental insults, personalize interventions, and extend healthspan.
    Keywords:  Dysbiosis; Gastrointestinal Microbiome; Host Microbial Interactions; Probiotics; Resilience
    DOI:  https://doi.org/10.1007/s12602-026-10976-1
  27. Quintessence Int. 2026 Mar 19. 0(0): 0
      Systemic lupus erythematosus (SLE) is a complex chronic autoimmune disease that can affect multiple organ systems, including the skin, joints, kidneys and oral cavity. In recent years, there has been growing interest in the oral health of patients with SLE, with studies showing that the incidence of dental caries, periodontal disease, oral mucosal lesions and salivary dysfunction is significantly higher in patients with SLE than in the general population. Factors such as immune system abnormalities, long-term use of glucocorticoids and immunosuppressants, and dysbiosis of the oral microbiome all contribute to an increased oral disease burden in patients with SLE. Oral health problems affect not only patients' nutritional intake, social interactions and self-esteem but may also create an inflammatory feedback loop exacerbating the underlying systemic condition. A multidisciplinary management approach involving rheumatology, dentistry and psychological support - with more refined and individualised strategies for prevention, treatment and follow-up - is crucial for patients with SLE. This review distinguishes itself from prior syntheses by systematically integrating the pivotal role of nursing teams within the multidisciplinary framework, and proposing actionable, structured protocols for assessment, referral, and long-term follow-up. Future research should focus on exploring the interaction between the oral microbiome and immune response mechanisms and strive to develop more effective interventions and standardised diagnostic and treatment protocols to improve the oral health and overall quality of life of patients with SLE.
    Keywords:  multidisciplinary advances; oral health management; systemic lupus erythematosus
    DOI:  https://doi.org/10.3290/j.qi.b6961709
  28. Front Microbiol. 2026 ;17 1800825
      
    Keywords:  ESKAPEE pathogens; antibiofilm strategies; antimicrobial resistance; biofilms; novel antimicrobials
    DOI:  https://doi.org/10.3389/fmicb.2026.1800825
  29. J Pain Res. 2026 ;19 563157
       Purpose: To retrieve, evaluate, and integrate the best available evidence on prevention and management of wound procedural pain management in patients with open wounds, providing evidence-based guidance for clinical practice.
    Patients and Methods: Following the "6S" pyramid model, we systematically searched guideline websites, professional association websites, and databases for guidelines, clinical decision aids, expert consensus statements, evidence summaries, recommended practices, and systematic reviews related to wound procedural pain management in patients with open wounds. The search period was from the establishment of the database to July 2025. Two researchers independently conducted literature quality assessment, evidence extraction, and synthesis.
    Results: A total of 23 documents were included: 5 guidelines, 1 expert consensus, 3 recommended practices, 3 clinical decisions, 6 evidence summaries, and 5 systematic reviews. Thirty-two best evidence statements were summarized across six aspects: pain assessment and documentation, education and training, dressing selection and replacement, wound cleansing, debridement, and negative pressure therapy, pharmacological intervention strategies, and non-pharmacological intervention strategies.
    Conclusion: This study reviews the best available evidence on managing procedural pain in open wounds. It offers guidance on the principles of pain management, standardization of procedural techniques, and the timely application of analgesic, emphasizing the importance of pain awareness. The research serves as a reference for developing specialized pain management protocols to improve wound care quality.
    Keywords:  clinical evidence; evidence-based nursing; open wounds; wound procedural pain
    DOI:  https://doi.org/10.2147/JPR.S563157
  30. Front Microbiomes. 2024 ;3 1396560
      The average American spends 93% of their time in built environments, almost 70% of that is in their place of residence. Human health and well-being are intrinsically tied to the quality of our personal environments and the microbiomes that populate them. Conversely, the built environment microbiome is seeded, formed, and re-shaped by occupant behavior, cleaning, personal hygiene and food choices, as well as geographic location and variability in infrastructure. Here, we focus on the presence of viruses in household biofilms, specifically in showerheads and on toothbrushes. Bacteriophage, viruses that infect bacteria with high host specificity, have been shown to drive microbial community structure and function through host infection and horizontal gene transfer in environmental systems. Due to the dynamic environment, with extreme temperature changes, periods of wetting/drying and exposure to hygiene/cleaning products, in addition to low biomass and transient nature of indoor microbiomes, we hypothesize that phage host infection in these unique built environments are different from environmental biofilm interactions. We approach the hypothesis using metagenomics, querying 34 toothbrush and 92 showerhead metagenomes. Representative of biofilms in the built environment, these interfaces demonstrate distinct levels of occupant interaction. We identified 22 complete, 232 high quality, and 362 medium quality viral OTUs. Viral community richness correlated with bacterial richness but not Shannon or Simpson indices. Of quality viral OTUs with sufficient coverage (614), 532 were connected with 32 bacterial families, of which only Sphingomonadaceae, Burkholderiaceae, and Caulobacteraceae are found in both toothbrushes and showerheads. Low average nucleotide identity to reference sequences and a high proportion of open reading frames annotated as hypothetical or unknown indicate that these environments harbor many novel and uncharacterized phage. The results of this study reveal the paucity of information available on bacteriophage in indoor environments and indicate a need for more virus-focused methods for DNA extraction and specific sequencing aimed at understanding viral impact on the microbiome in the built environment.
    Keywords:  biofilm; built environment; host-phage interaction; mycobacteria; virome
    DOI:  https://doi.org/10.3389/frmbi.2024.1396560
  31. Clin Podiatr Med Surg. 2026 Apr;pii: S0891-8422(25)00122-3. [Epub ahead of print]43(2): 195-209
      Diabetes mellitus affects nearly 600 million adults worldwide and frequently leads to complications such as diabetic foot ulcers (DFU), driven by neuropathy, ischemia, infection, and impaired wound healing. Biomarkers have emerged as essential tools to improve early diagnosis, risk stratification, and management. Inflammatory markers like CRP, IL-6, and TNF-α, along with oxidative stress indicators such as MDA and 8-OHdG, highlight chronic inflammation and cellular damage in nonhealing wounds. Wound surface area trends and metabolic markers-including HbA1c, fasting glucose, and CGM metrics-further guide prognosis.Integrating these biomarkers may enable personalized interventions and reduce DFU-related morbidity and amputation risk.
    Keywords:  Biomarkers; Diabetic foot ulcers (DFU); Glycemic control; Inflammation; Wound healing
    DOI:  https://doi.org/10.1016/j.cpm.2025.12.007
  32. Sci Adv. 2026 Mar 20. 12(12): eadz0786
      Wound infections are becoming increasingly difficult to treat due to rising antibiotic-resistant bacteria. β-Lactamase-producing bacteria are among the most common pathogens implicated in these infections. Here, we report a bacterial enzyme-responsive hydrogel formulated with a cephalosporin-derived, β-lactamase-cleavable crosslinker that undergoes selective degradation in the presence of bacterial β-lactamases. This degradation triggers the on-demand release of encapsulated ciprofloxacin-loaded liposomes, ensuring that antibiotic delivery occurs only at the site of infection. This selective degradation and release was demonstrated in both ex vivo and in vivo models of Pseudomonas aeruginosa wound infections. In a murine skin abrasion infection model, a single application of the hydrogel led to complete bacterial eradication and enhanced wound healing, outperforming a commercial silver-based hydrogel wound dressing. These responsive hydrogels did not induce ciprofloxacin resistance in non-β-lactamase-producing bacteria. These findings demonstrate that β-lactamase-responsive hydrogels provide a precise, infection-triggered antibiotic delivery platform that can improve the treatment of wound infections and mitigate antimicrobial resistance.
    DOI:  https://doi.org/10.1126/sciadv.adz0786
  33. Front Cell Dev Biol. 2026 ;14 1794273
      Diabetic foot osteomyelitis (DFO) often manifests as persistent, non-healing infection with progressive bone destruction. Poor glycemic control and concomitant peripheral vascular and neuropathic injury are key drivers. Effective clinical solutions remain limited. Current management typically involves debridement of infected and necrotic tissues, local or systemic antibiotics, and bone/soft-tissue reconstruction. However, impaired local circulation makes it difficult to sustain therapeutic antibiotic levels at the lesion site. Recurrence is therefore common. Bone regeneration is also hard to achieve, which prolongs the overall course and results in repeated procedures, long recovery cycles, and high costs. To overcome these limitations, we propose a microenvironment-matched strategy as a practical direction for DFO therapy. The DFO niche is characterized by bacterial persistence and recurrent infection, severe oxidative stress and chronic inflammation, immunometabolic dysregulation, and microvascular plus neural injury that suppress osteogenesis. These constraints converge on three intertwined therapeutic targets: infection, inflammation, and bone defects. Treatment should thus be precise, sequential, and coordinated across targets, rather than relying on isolated interventions. This review systematically summarizes advances in multitarget antibacterial approaches, anti-inflammatory and immunometabolic modulation, and multifunctional biomaterial platforms that integrate angiogenesis, neurorestoration, and osteogenic regeneration. We further highlight microenvironment-responsive, integrated strategies that optimize drug dosing and release timing, aiming to improve the durability of infection control and the quality of bone reconstruction. Ultimately, we provide researchers with testable material design and synthesis logic, and offer clinicians new therapeutic paradigms and stage-adaptive, precision care pathways.
    Keywords:  bone tissue engineering materials; diabetic foot osteomyelitis (DFO); multi-target therapy; pathological microenvironments; tailored treatment strategies
    DOI:  https://doi.org/10.3389/fcell.2026.1794273
  34. Front Microbiomes. 2025 ;4 1549166
      The human respiratory tract microbiome is a multi-kingdom microbial ecology that inhabits several habitats along the respiratory tract. The respiratory tract microbiome promotes host health by strengthening the immune system and avoiding pathogen infection. The lung microbiome mostly originates in the upper respiratory tract. The balance between microbial immigration and removal determines the nature of the lung microbiome. Identification and characterization of microbial communities from airways have been made much easier by recent developments in amplicon and shotgun metagenomic sequencing and data analysis techniques. In pulmonary medicine, there is a growing interest in the respiratory microbiome, which has been linked to human health and illness. However, the primary causes of bacterial co-occurrence seem to be interactions with fungi and bacteria as well as host and environmental factors. This study focused on identifying techniques and the current understanding of the relationship between the microbiota and various lung diseases.
    Keywords:  dysbiosis; microbiota; next generation sequencing; omics tools; respiratory tract
    DOI:  https://doi.org/10.3389/frmbi.2025.1549166
  35. Antimicrob Agents Chemother. 2026 Mar 16. e0106224
      Candida auris has garnered substantial clinical and public health attention for its widespread antifungal resistance. Most isolates are resistant to fluconazole, and many, to other drug classes, with acquired resistance to all clinically available antifungal drugs reported. Antifungal resistance is rising alongside increasing case counts, threatening a sparse antifungal toolbox with multidrug and pan-resistant isolates that may cause untreatable infections. In this minireview, we examine the recent literature investigating the mechanisms and evolutionary patterns of resistance in clinical isolates of C. auris to each antifungal utilized to combat these infections. We propose a refined model of C. auris drug resistance by separating the multidrug resistance paradigm into distinct resistance challenges for each drug class. We examine how the emergence of unique resistance patterns to each drug may suggest therapeutic options even for currently available antifungals. Resistance to fluconazole is driven by drug target mutations with clade-specific representation and more diverse acquired mutations in drug efflux regulators. Recent structural insights into the context of these mutations may suggest vulnerabilities to other triazoles even in fluconazole-resistant strains. Acquired resistance to echinocandins, amphotericin B, and the pyrimidine analog flucytosine is rare but can emerge under antifungal therapy through conserved resistance mechanisms. The reportedly higher amphotericin B resistance rate in C. auris relative to other Candida species remains poorly understood and may be linked to unexplored intrinsic resistance mechanisms. We suggest that close examination and further investigation of these mechanisms may inform better therapeutic practice and may offer treatment solutions for this multidrug-resistant pathogen.
    Keywords:  Candida auris; drug resistance; fungal genetics
    DOI:  https://doi.org/10.1128/aac.01062-24
  36. Infection. 2026 Mar 19.
       PURPOSE: Periodontal disease is a chronic inflammatory condition increasingly associated with cardiovascular disease (CVD) beyond shared risk factors. This review evaluates evidence linking periodontal inflammation to cardiovascular outcomes and identifies periodontal biomarkers with potential relevance for cardiovascular risk assessment.
    METHODS: A narrative review was conducted using PubMed, Scopus, and Web of Science databases, including studies published between 1990 and 2025. Epidemiological, clinical, and mechanistic studies examining associations between periodontal disease, inflammatory and microbial biomarkers, and cardiovascular outcomes were included. Biomarkers were categorized as inflammatory cytokines, acute-phase proteins, oxidative stress markers, lipid mediators, and microbial indicators. Evidence regarding periodontal therapy and emerging point-of-care diagnostic technologies was also reviewed.
    RESULTS: Epidemiological studies demonstrate increased risks of coronary heart disease, stroke, and atherosclerosis in individuals with periodontitis, independent of traditional cardiovascular risk factors. Mechanistic evidence indicates that periodontal pathogens and host immune responses promote systemic inflammation, endothelial dysfunction, and atherogenesis. Key biomarkers associated with cardiovascular outcomes include cytokines (IL-1β, IL-6, TNF-α, IL-17), acute-phase proteins (C-reactive protein, fibrinogen), matrix-degrading enzymes such as active matrix metalloproteinase-8, oxidative stress markers (myeloperoxidase, malondialdehyde), lipid mediators (lipoprotein-associated phospholipase A2), and microbial markers such as antibodies to Porphyromonas gingivalis. Periodontal therapy has been associated with reductions in systemic inflammatory markers and improvements in endothelial function, although large, randomized trials remain limited.
    CONCLUSION: Periodontal biomarkers reflect biologically plausible mechanisms linking oral and cardiovascular inflammation and may enhance cardiovascular risk stratification. Further standardization, validation, and interdisciplinary collaboration are required for clinical translation.
    Keywords:  Biomarkers; C-reactive protein; Cardiovascular diseases; Interleukin-6; Myeloperoxidase; Periodontitis
    DOI:  https://doi.org/10.1007/s15010-026-02778-y