Gut microbiota dysbiosis driven by pathogenic and opportunistic bacteria, including Clostridioides difficile, adherent-invasive Escherichia coli (AIEC), Salmonella enterica serovar Typhimurium, Fusobacterium nucleatum, Klebsiella pneumoniae, Enterococcus faecalis, and Campylobacter spp., disrupts colonization resistance, epithelial barrier integrity, and immune homeostasis, thereby contributing to the development of inflammatory and metabolic diseases. In this review, we summarize the mechanisms through which these microorganisms promote gut dysbiosis and critically evaluate current microbiome-targeted therapeutic strategies, including fecal microbiota transplantation (FMT), live biotherapeutic products (LBPs), probiotics, and bacteriophage (phage) therapy. We review the preclinical and emerging clinical evidence supporting phage-based targeting of major dysbiosis-associated pathogens and examine the principal challenges limiting clinical translation, including phage resistance, immune-mediated clearance, safety considerations related to temperate phages, manufacturing and delivery constraints, and regulatory barriers. Although evidence remains predominantly preclinical, advances in phage engineering, artificial intelligence-guided phage selection, and systems-level microbiome modeling are expanding the potential of personalized phage therapeutics. Collectively, these developments position bacteriophage therapy as a promising addition to future microbiome-directed strategies for restoring gut microbial homeostasis and managing dysbiosis-associated disease.

The oral cavity is the second most colonized anatomical site after the intestinal tract, and due to its unique and diverse microbial community, it constitutes a distinct biome. The oral microbiota is an integral part of the human microbiome ecosystem, maintaining the balance of the oral microecology. However, when this balance of the oral microecology is disrupted, oral bacteria not only cause oral diseases but also spread to other parts of the body through various pathways. These oral bacteria colonizing outside the oral cavity may exhibit different functional roles from those in the oral cavity, thereby contributing to or exacerbating pathological processes in distant organs, such as experimental colitis, hepatic steatosis, and opportunistic bacteremia. By analyzing compositional changes in the oral and gut microbiota, the risk of certain diseases can be predicted at an early stage, and timely interventions can be implemented. This review summarizes the colonization and disease-causing effects of several major oral bacteria (Streptococcus, Veillonella, Prevotella, Lactobacillus, Helicobacter pylori, Fusobacterium nucleatum, Porphyromonas gingivalis, Tannerella forsythia) in the oral cavity and other sites. To provide conceptual rigor, we explicitly distinguish among passive ectopic detection, stable ectopic colonization, and functionally active pathogenicity. Furthermore, we highlight how ectopic oral bacteria undergo context-dependent metabolic adaptations in new niches, rather than simply replicating their oral profiles.

Cisplatin remains a cornerstone of head and neck cancer (HNC) treatment, yet resistance frequently undermines therapeutic efficacy. Emerging evidence implicates Fusobacterium nucleatum, enriched in the tumour microbiome, in promoting chemoresistance via molecular and microenvironmental mechanisms. This review synthesises evidence from PubMed, Scopus, and Web of Science (January 2015-September 2025) examining F. nucleatum's contribution to cisplatin resistance in HNC. Cisplatin resistance involves tumour-intrinsic pathways, such as nucleotide excision repair, homologous recombination, and ATP7B-mediated drug efflux. F. nucleatum indirectly enhances resistance via Wnt5a/Ca[2+]-NFATc3 signalling, downregulation of p53 and E-cadherin, and activation of the NLRP3 inflammasome, which recruits myeloid-derived suppressor cells. It also amplifies inflammation and chemoresistance by escalating the senescence-associated secretory phenotype, promoting a tumour-supportive microenvironment. These findings highlight microbiome host crosstalk as a therapeutic target, suggesting that microbiota-directed strategies alongside cisplatin may improve outcomes in resistant HNC.

Periodontal dysbiosis is characterized by a shift towards specific obligate anaerobic bacteria, capable of inducing persistent, low-grade systemic inflammation. Increasing evidence links oral anaerobes to increased vascular risk and neuroinflammatory pathways. We present the case of a 45-year-old, previously healthy, Caucasian male, enrolled as a control subject in a prospective clinical study, exhibiting poor oral hygiene, generalized gingival inflammation, bleeding on probing: 56.79%, plaque index: 85.18%, and a 7 mm periodontal pocket. Anaerobic culture from subgingival plaque sampling revealed the presence of Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella buccae, Veillonella parvula and Veillonella rogosae (V. rogosae). Concurrently, elevated serum high-sensitivity C-reactive protein (hsCRP) (6.3 mg L-1) was also detected. Prior to scheduled follow-up, the patient developed a spontaneous subarachnoid hemorrhage, where neuroimaging and angiography did not identify a vascular source. After recovery, periodontal therapy and cessation of all tobacco products, subgingival anaerobic diversity markedly decreased, with persistent detection of V. rogosae only; in addition, hsCRP also normalized. Although causality cannot be established, our case highlights systemic inflammatory implications of periodontal dysbiosis - and underlying neuroinflammatory processes - and demonstrates that periodontal therapy may be crucial in normalizing systemic inflammatory markers, effectively contributing a decreased disease burden through multiple pathways.

Infection with Helicobacter pylori is the major risk factor for gastric cancer worldwide; yet the exact mechanisms behind this link remain unclear. H. pylori-associated tissue changes often disrupt the gastric microbiome, enabling secondary gastric colonization by oral bacteria. Among these secondary colonizers, Fusobacterium species have documented associations with several gastrointestinal cancers. We found that both F. animalis and F. nucleatum invade cultured human gastric adenocarcinoma cells, but F. animalis exhibited higher adherence and invasion, and hypoxic conditions promoted higher bacterial survival. Both adherence and invasion were inhibited by exogenous GalNAc, a glycan commonly observed in membrane glycoproteins of adenocarcinoma cells and a target of the fusobacterial adhesin Fap2. Using a mouse model of stomach metaplasia, we found that F. animalis colonized gastric tissue only after metaplasia onset, growing in multispecies biofilms in the mucus layer, while F. nucleatum colonized neither healthy nor metaplastic gastric tissue. Metaplasia led to upregulation of Gal-GalNAc in the stomach, and reduced gastric acidity allowed higher F. animalis loads in this model. By contrast, inflammation and the presence of H. pylori did not significantly influence stomach colonization by F. animalis. Further assessment of additional Fusobacterium species and strains revealed that whereas all tested species can invade gastric cancer cells in vitro, only F. animalis and F. polymorphum robustly colonize the metaplastic gastric tissue of the mouse model similar to F. animalis. Overall, our data support a model in which H. pylori-induced metaplasia makes the stomach susceptible to secondary infection by other cancer-associated microbes, including some Fusobacterium species.IMPORTANCEHelicobacter pylori infection is the primary risk factor for gastric cancer worldwide, yet the underlying cancer-promoting mechanisms are not fully defined. Our study shows that metaplasia, a precancerous condition typically triggered by H. pylori and characterized by specific changes in gene expression and tissue remodeling, can enable secondary infection by other cancer-associated bacteria. Specifically, we found that certain species of the genus Fusobacterium, linked to several gastrointestinal cancers, colonize the stomach only after the onset of metaplasia. Metaplasia-associated changes in the stomach include altered surface sugars and reduced acidity, which together may create a more permissive environment for bacterial growth. Our findings support a model in which disruptions of gastric tissue architecture induced by chronic H. pylori infection facilitate colonization by other cancer-related bacteria, contributing to the growing body of evidence highlighting the role of bacteria in cancer development.

This meta-analysis was conducted to assess the effects of probiotics on dental plaque, gingival health, and the oral microbiological environment. PubMed and Google Scholar were searched, and the Cochrane Collaboration's Risk of Bias tool was used to assess the risk of bias in the included studies. Thirteen randomised clinical trials were included, enrolling 321 participants. Probiotics had positive effects on gingival index (GI) scores (p = 0.04), with no statistically significant improvement in plaque index scores (p = 0.64) or bleeding on probing (p = 0.92). No significant differences were observed in IL-1β levels; Prevotella intermedia (p = 0.37), Fusobacterium nucleatum (p = 0.11), Porphyromonas gingivalis (p = 0.13), Aggregatibacter actinomycetemcomitans (p = 0.16) counts; or gingival crevicular fluid volumes (p = 0.94). The probiotics intervention had a substantial impact on GI score. These findings suggest that probiotics may improve gingival health and offer adjunctive treatment for gingivitis and periodontal disease. Key Words: Dental plaque, Gingival health, Microbiological environment, Oral, Probiotics.

Periodontal disease and lung cancer are major global health burdens, and epidemiological evidence suggests a potential association between them. However, whether this relationship is independent of smoking-a strong common risk factor-remains controversial. This review systematically summarizes current evidence on the association, with emphasis on smoking confounding and underlying biological mechanisms. Meta-analyses consistently show a significant positive association, with adjusted hazard ratios ranging from 1.24 to 1.71 and dose-response relationships across disease severity and tooth loss. After rigorous statistical adjustment for smoking, most large cohort studies still show a robust association, though findings in never-smokers are inconsistent, suggesting possible residual confounding. Mechanistically, the "oral-lung axis" links periodontitis to lung carcinogenesis via three pathways: microbial translocation of pathogens such as Fusobacterium nucleatum, chronic inflammation-driven immune dysregulation involving Treg and IL-6, and epigenetic modifications including shared DNA methylation sites. Smoking may also act synergistically with periodontitis to amplify carcinogenic risk. Future research should prioritize precisely quantified smoking exposure, formal interaction analyses, and longitudinal multi-omics studies to support causal inference. This review provides a theoretical foundation for incorporating oral health assessment into lung cancer prevention strategies.

Gastric cancer (GC) is closely associated with microbial dysbiosis; however, the spatial-temporal characteristics of the gut, paracancerous, and intratumoral microbiomes, as well as their interrelationships during tumor progression, remain insufficiently defined. This study aimed to characterize these microbiomes in 85 GC patients from Northwest China using shotgun metagenomic sequencing and functional annotation. Clinical samples included feces, tumor tissues, and paratumor mucosal tissues (≥5 cm from the tumor margin), enabling comprehensive profiling of microbial composition at the phylum, genus, and species levels, as well as functional pathway analysis. The results showed that the microbial community was dominated by Firmicutes and Bacteroidetes (combined relative abundance >75%), maintaining structural stability across tumor stages II-IV (Stage I n=2 is only descriptively reported and excluded from formal statistical testing), thereby supporting the "core microbiota resilience" hypothesis. PERMANOVA revealed that tumor stage had a statistically significant yet modest effect on community structure (R[2] = 0.039, P = 0.032). MaAsLin2 identified stage-associated differential genera: Roseburia and Megamonas decreased with advancing stage, whereas Lactobacillus and Enterobacter were enriched in advanced stages (III/IV). Functional pathway analysis revealed stage-specific metabolic remodeling: Stage II was enriched in DNA repair, glycolysis, aromatic amino acid, and nucleotide biosynthesis pathways; Stage IV showed enrichment in protein deamination/demethylation, pyruvate fermentation, and coenzyme metabolism pathways. Correlation analysis further revealed a characteristic pattern of "pathogen enrichment and beneficial bacteria depletion." Fusobacterium nucleatum and Helicobacter pylori exhibited strong positive correlations with GC, whereas short-chain fatty acid-producing bacteria such as Roseburia and Faecalibacterium prausnitzii showed significant negative correlations, particularly in paracancerous tissues. We established multi-layered taxonomic correlation profiles based on intra-cohort microbial shifts, in which Bacteroides stercoris and Bifidobacterium pseudocatenulatum exhibited the most pronounced stage-related abundance changes in the fecal microbiota across tumor stages. Overall, this study systematically delineates the structural stability, stage-specific functional remodeling, and interrelated dynamics of gut, paracancerous, and intratumoral microbiomes in gastric cancer. These findings provide descriptive baseline data of cross-compartment microbiome variation within gastric cancer patients across tumor stages, which only deliver preliminary correlative clues of GC-related microbial shifts and require further multi-cohort verification with non-cancer control populations.

Gut dysmotility is a common long-term effect of enterotoxigenic Bacteroides fragilis (ETBF) colonization but the underlying mechanisms are not clear. Here, using mouse colonization models, we found that ETBF-secreted B. fragilis toxin (BFT) causes loss of colonic myenteric neurons, which are crucial regulators of intestinal motility. BFT induced apoptosis in these neurons through the NOD1-RIPK2-CASP9-CASP3 pathway, leading to gut dysmotility that persisted even after the clearance of ETBF. Analyses of human inflammatory bowel disease and colorectal cancer patient cohorts showed a positive correlation between ETBF and Fusobacterium nucleatum abundance. In mice, F. nucleatum-derived 2-hydroxybutyric acid enhanced BFT production in ETBF by alleviating RprY-mediated suppression and aggravated neurotoxicity and dysmotility. This enteric neuron loss and dysmotility enhanced susceptibility to dextran sulfate sodium-induced colitis in mice. Therapeutically, a Bifidobacterium-based probiotic attenuated neuron toxicity and improved intestinal motility. Our findings reveal bacterial interactions regulating intestinal function and a potential clinical therapeutic approach to preventing outcomes of ETBF colonization.

A topical mucoadhesive dosage form was developed for the treatment of infectious oral cavity diseases, consisting of a paste based on a combination of a complex immunoglobulin preparation (CIP) and interferon alpha-2b. CIP within the final formulation demonstrated robust antimicrobial activity against key oral pathogens (Staphylococcus aureus, Streptococcus intermedius, and Fusobacterium nucleatum). An optimal composition was selected that exhibited optimal mucoadhesion and a mucosal retention time of at least 90 min. The final formulation produced no local irritant effects.

CRC is the third most prevalent malignancy worldwide and the second leading cause of cancer-related mortality. According to GLOBOCAN 2022 estimates, approximately 1.93 million new CRC cases and 900,000 CRC-related deaths occur annually worldwide. Incidence rates continue to rise in developing countries, driven by the westernization of dietary patterns, sedentary lifestyles, and increasing obesity prevalence, with a notable trend toward younger-onset disease. In recent years, mounting evidence has implicated the microbiota as a critical contributor to CRC initiation and progression. Distinct from the fecal microbiome, the intratumoral microbiome constitutes an independent, low-biomass microbial community predominantly composed of bacteria, with additional fungal, viral, and archaeal components. Microbial communities within the TME promote CRC development and progression by modulating host immune responses, metabolic pathways, and tumor cell proliferation and metastasis. Fusobacterium nucleatum, ETBF, polyketide synthase genotoxicity island-harboring Escherichia coli and Parvimonas micra represent the most well-substantiated candidate oncomicrobes, whose carcinogenic activities involve multiple intertwined pathways, including chronic inflammation, genotoxic DNA damage, immune evasion, metabolic reprogramming, and non-coding RNA regulation. Furthermore, intratumoral microbiota may serve as early diagnostic biomarkers for CRC, offer novel therapeutic targets, and provide potential biological rationale for prognostic prediction. Microbiome-based diagnostic biomarkers, such as multi-bacterial fecal/tissue panels, have demonstrated sensitivity comparable to or superior to the fecal immunochemical test in select retrospective cohorts; however, large-scale, multicenter, prospective validation remains necessary. Strategies targeting intratumoral bacteria - including antibiotics, bacteriophages, phage-guided nanocarriers, and FMT - remain predominantly in the preclinical stage. Although phase I/II trials of FMT for immunotherapy sensitization have yielded encouraging results, small sample sizes and substantial heterogeneity preclude its near-term adoption as a standard-of-care recommendation. This review systematically summarizes the latest advances in understanding the relationship between intratumoral microbiota and CRC, critically appraises the strength of evidence across different hierarchical levels, evaluates the consistency and controversies surrounding major mechanistic hypotheses, addresses methodological challenges inherent to low-biomass microbiome research, and discusses the translational potential in CRC diagnosis, therapy, and prognostic prediction.

Oral squamous cell carcinoma (OSCC) develops within a complex inflammatory microenvironment where chronic mucosal inflammation and microbial dysbiosis may contribute to malignant transformation. Increasing evidence suggests that periodontal pathogens associated with chronic gingival inflammation can influence epithelial signaling, immune responses, and tumor progression. This scoping review aimed to map current molecular, genomic, and immunological evidence linking chronic gingival inflammation and periodontal pathogen-associated dysbiosis to OSCC. Following the Population-Concept-Context (PCC) framework, electronic searches were conducted in PubMed, Scopus, and Web of Science through February 2026. Original studies investigating mechanistic links between periodontal inflammation, microbial dysbiosis, and OSCC in human samples, in vitro models, or animal models were included. Data were extracted on microbial drivers, oncogenic signaling pathways, immune modulation, and genomic or epigenetic alterations. A total of 46 studies were included, suggesting that periodontal pathogens, particularly Porphyromonas gingivalis and Fusobacterium nucleatum, may activate oncogenic signaling pathways such as NF-κB, PI3K/Akt, Wnt/β-catenin, and TGF-β. Evidence from in vitro, animal, and human studies indicates that these pathways may contribute to epithelial-mesenchymal transition (EMT), tumor invasion, and resistance to apoptosis. Microbial exposure has also been associated with modulation of the tumor immune microenvironment, including macrophage polarization, suppression of cytotoxic T-cell responses, and enhanced immune checkpoint signaling. In addition, genomic and transcriptomic studies have identified dysregulated genes and microRNAs associated with inflammation-driven carcinogenesis. Overall, chronic gingival inflammation and periodontal dysbiosis appear to contribute to OSCC development through interconnected mechanisms involving inflammatory and cytokine signalling, microbe sensing and innate immune activation, immune suppression and tumor immune escape, EMT, invasion and metastatic signaling, and metabolic reprogramming with regulatory networks. However, as current evidence is largely derived from in vitro and animal studies with limited prospective clinical data, well-designed longitudinal human studies are needed to confirm these associations and support biomarkers discovery and novel preventive or therapeutic strategies targeting early oncogenic events in inflamed oral tissues.