Gut Pathogens最新文献

Tropical sprue, a rare malabsorption syndrome, remains a significant yet underrecognized gastrointestinal disorder endemic to tropical regions, including South and Southeast Asia (e.g., India, Pakistan) and Caribbean islands (e.g., Puerto Rico, the Dominican Republic, Haiti). Its etiology remains uncertain, but mounting evidence supports an infectious origin, with bacterial overgrowth involving pathogens such as Alcaligenes, Klebsiella, and Enterobacter species frequently implicated. The disease causes profound intestinal alterations that impair the absorption of vitamin B12, fat-soluble vitamins (A, D, E, and K), and minerals such as calcium and magnesium, frequently resulting in chronic diarrhea and severe nutritional deficiencies. Histologically, villous atrophy of the jejunal and ileal mucosa is a hallmark feature. This narrative review synthesizes current knowledge on the epidemiology, etiology, intestinal pathophysiology, and histopathology of tropical sprue, while highlighting diagnostic challenges and the urgent need for further research to elucidate its pathogenesis and improve clinical management in endemic settings.

Background: Helicobacter pylori infection, linked to peptic ulcer disease and gastric cancer, faces declining eradication rates due to antibiotic resistance. High-dose esomeprazole-amoxicillin dual therapy (HDDT) is a promising rescue regimen, but its efficacy and safety compared to standard therapies remain unclear.

Methods: This systematic review and meta-analysis, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, included four randomized controlled trials (n = 1,230) that compared HDDT with standard regimens. PubMed, Embase, and Cochrane CENTRAL were searched through April 2025. Outcomes included eradication rates, compliance, and adverse events. A meta-analysis was conducted using the inverse variance method, with heterogeneity assessed via I² statistics.

Results: HDDT showed no significant difference in eradication rates (RR = 0.98, 95% CI: 0.89-1.08, P = 0.6438) or compliance (RR = 1.04, 95% CI: 0.97 to 1.12, P = 0.2522) compared to standard therapies. However, HDDT significantly reduced overall adverse events (RR = 0.28, 95% CI: 0.18-0.44, P < 0.0001), including nausea, headache, fatigue, dysgeusia, bloating, and abdominal pain. No significant differences were observed for serious adverse events, diarrhea, dizziness, decreased appetite, constipation, or skin rash. Heterogeneity varied across the outcomes.

Conclusion: HDDT is as effective as standard regimens for H. pylori rescue treatment, with a superior safety profile, supporting its use in patients with prior treatment failures.

Background: Species-level resolution is essential to understand gastric microbiome recovery after Helicobacter pylori eradication, yet short-read 16 S rRNA approaches often obscure clinically relevant changes.

Methods: Gastric biopsies from 121 adults in Bayan-Ölgii, Mongolia (71 H. pylori-positive, 50 H. pylori-negative) were analyzed, including nine paired pre- and post-eradication gastric biopsy samples collected six months apart, enabling exploratory longitudinal analysis. Full-length 16 S rRNA (V1-V9) sequencing was performed using the Oxford Nanopore platform with EMU taxonomic assignment (SILVA v138.1/NCBI RefSeq). Ecological changes were evaluated using diversity indices, principal coordinates analysis (PCoA) with PERMANOVA, and differential abundance testing (DESeq2, FDR < 0.05). Eradication therapy (esomeprazole-bismuth-doxycycline-levofloxacin) achieved success in 54 of 57 H. pylori-positive patients (94.7%).

Results: H. pylori-positive microbiomes were dominated by H. pylori (91.8% ± 3.9%) and exhibited markedly reduced diversity (Shannon = 0.44 ± 0.11) compared with H. pylori-negative samples (2.08 ± 0.25; p < 0.001). Six months after eradication, diversity increased significantly (2.17 ± 0.20; p = 0.0001), with enrichment of oral commensals including Streptococcus mitis (↑ 11.9×), Neisseria elongata (↑ 13.7×), and Prevotella melaninogenica (↑ 13.0×). However, post-eradication profiles at six months remained distinct from H. pylori-negative communities (PERMANOVA R² = 0.12; p = 0.02). In total, 174 amplicon sequence variants changed significantly, including persistence of Fusobacterium nucleatum.

Conclusions: Nanopore full-length 16 S sequencing reveals fine-scale, clinically relevant shifts that are masked by partial-gene assays. Eradication rapidly restores microbial diversity, but at six months, is associated with a novel ecological equilibrium rather than complete normalization. This species-resolved approach offers a practical framework for post-eradication microbiome monitoring and may inform strategies to reduce residual gastric cancer risk in high-burden populations.

The gut microbiome has become a primary controller of host immunity as well as the pathogenesis of human immunodeficiency virus (HIV) infection. Commensal microbes in healthy persons keep the intestinal and other body barriers intact and regulate mucosal and systemic immune responses and generate metabolites, including short-chain fatty acids and indole derivatives that suppress inflammation and stimulate epithelial healing. These functions are impaired by HIV infection via depletion of gut CD4 + T cells, damage caused to epithelium, microbial translocation, and microbiota disruption. In this review article, we summarize recent studies suggesting that a balanced microbiome can mitigate HIV susceptibility and progression by preserving mucosal defenses, limiting systemic immune activation, and generating antiviral compounds. Other interventions, including probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation (FMT), have been trialed with mixed outcomes in most cases, showing small but significant changes in the gut microbial composition and/or inflammatory markers. Current evidence highlights the potential of microbiome-targeted strategies to support HIV management; however, substantial gaps remain. Future research should focus on defining protective microbial signatures, developing next-generation live biotherapeutics, exploring metabolite-based therapies, and conducting large, mechanistically driven clinical trials. Harnessing the microbiome's protective functions could offer novel approaches to reducing HIV transmission, mitigating inflammation, and improving immune reconstitution in infected individuals.

Akkermansia muciniphila (A. muciniphila), a health-promoting bacterium in the human gut, is recognized for its role in improving immune function and metabolic health. Recent studies have uncovered its potential use as a therapeutic intervention for cancer treatment. This meta-analysis examines the impact of A. muciniphila, its extracellular vesicles (EVs), and Amuc protein on cancer outcomes in preclinical cancer models. Sixteen studies were included in the analysis through searches of relevant databases as of July 2025. Data on tumor number, volume, weight, and immune responses were extracted and analyzed. A. muciniphila and its derivatives significantly reduced tumor metrics across various cancers, including intestinal, colorectal, prostate, lung, gastric, hepatocellular, and ovarian. The intervention elevated interferon-gamma (IFNγ), CD8⁺ T cells, TNFα, and reduced IL-10 in the tumor microenvironment. Reduced spleen weight and systemic IL-6 levels indicated both local and systemic modulation of inflammation. Dose-specific effects included more substantial reductions in tumor number, size, and spleen weight at low doses (≤ 10⁸ CFU), as well as decreased tumor cell proliferation at high doses (≥ 10⁹ CFU). A. muciniphila and its derivatives exhibit significant potential in reducing cancer metrics. Their effects are mediated by regulating tumor growth, modulating both tumor microenvironment and systemic inflammatory pathways, enhancing immune regulation, and affecting gut microbiota composition. These results suggest that A. muciniphila may be a promising next-generation adjunct therapy for cancer, particularly in its non-live forms. Further exploration of the role of A. muciniphila's outer membrane proteins and metabolites through comprehensive clinical studies could unlock new therapeutic opportunities.

Background: Acute appendicitis is associated with characteristic changes in the intestinal microbiota, but direct sampling of appendiceal contents is invasive and cannot be performed in healthy controls. We therefore evaluated whether rectal swabs could partially capture appendiceal microbiome signatures in adults with acute appendicitis.

Methods: In a prospective cross-sectional study, we enrolled adults with acute appendicitis and healthy volunteers between October 2023 and December 2024. Four types of samples were collected: feces from healthy controls (HC), appendiceal luminal contents from patients with acute appendicitis (AC), intraoperative rectal swabs from patients with acute appendicitis (RS), and initial postoperative feces from patients with acute appendicitis (IF; first stool within 24 h after surgery). 16 S rRNA gene (V3-V4) sequencing was performed, and reads were processed with QIIME2. Alpha and beta diversity, differential taxonomic composition, and PICRUSt2-based functional predictions were compared across matrices. Genus-level and functional concordance between paired AC-RS samples was assessed.

Results: After quality control, 64 AC, 34 RS, 24 IF, and 29 HC samples were included. Phylogenetic diversity (PD whole-tree) was higher in AC and RS than HC, with AC also higher than RS; IF showed lower PD than AC. Bray-Curtis principal coordinate analysis showed AC forming a distinct cluster separated from HC and RS along PC1, whereas IF overlapped with HC and RS. AC, RS, and IF were enriched for Escherichia/Shigella and Fusobacterium and depleted in butyrate-producing genera such as Faecalibacterium compared with HC. In the 21 paired AC-RS cases, genus-level relative abundances and several predicted functional pathways showed concordance, indicating that RS captured many but not all appendiceal dysbiosis features.

Conclusions: Our findings suggest that intraoperative rectal swabs may partially reflect appendiceal microbiome alterations at the genus and pathway levels and may serve as a minimally invasive adjunct for microbiome profiling in acute appendicitis. However, these associations are inferred from 16 S amplicon data in a modestly sized, antibiotic-exposed cohort and should be validated using shotgun metagenomics in larger, clinically stratified populations.

Current improvements in microbiome research have illuminated the serious function of probiotics in modulating host gene expression through epigenetic mechanisms, particularly via the regulation of non-coding RNAs (ncRNAs) such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). These regulatory RNAs are essential mediators of gene silencing, chromatin remodeling, and cellular signaling pathways implicated in immunity, inflammation, cancer, and neurodegenerative diseases. This review comprehensively examines current evidence on how specific probiotic strains influence miRNA and lncRNA expression, leading to beneficial outcomes in various pathological and physiological conditions. We explore the underlying molecular mechanisms by which probiotic-derived metabolites, like extracellular vesicles and short-chain fatty acids, interrelate with host transcriptional machinery and ncRNA biogenesis. Special emphasis is placed on disease models including inflammatory bowel disease, colorectal cancer, metabolic syndrome and Alzheimer's disease, highlighting the beneficial possible of targeting the gut microbiota-ncRNA axis. Moreover, we discuss the prospects for personalized microbiome-based interventions, challenges in clinical translation, and future directions for leveraging probiotic-ncRNA interactions in precision medicine. The integration of probiotics into epigenetic therapy represents a promising, non-invasive strategy for modulating gene expression and restoring homeostasis in complex diseases.

Background: Antibiotic resistance poses a major challenge in treating Vibrio cholerae infections. One promising method to counter resistance is the co-administration of antibiotics with non-antibiotic adjuvants to enhance their efficacy. This study investigated the combined action of sodium butyrate (SB) and tetracycline on tetracycline-resistant V. cholerae strains.

Results: The combined activity of SB and antibiotics was assessed on eight V. cholerae clinical isolates using the Fractional Inhibitory Concentration Index (FICI), with SB-Tetracycline showing strong synergy (FICI: 0.09-0.5). Functional and mechanistic studies, including time-kill kinetics, live/dead staining, SEM-based morphological analysis, and fluorometric assays, demonstrated a synergistic antibacterial effect of SB and Tetracycline. This effect was associated with increased membrane permeability, disruption of membrane integrity, dissipation of the proton motive force, and suppression of efflux activity. These changes collectively led to membrane damage, enhanced intracellular accumulation of Tetracycline, decreased intracellular ATP levels, and ultimately, bacterial cell death. Moreover, GM₁-CT ELISA and fluorescence microscopy revealed the synergistic anti-virulence activity of the SB- Tetracycline combination. Finally, the combination of SB and Tetracycline showed enhanced efficacy in animal models compared with monotherapy.

Conclusion: The observed SB-Tetracycline synergy provides a promising therapeutic approach to overcome tetracycline resistance in V. cholerae, offering a potential adjunct strategy for the management of antibiotic-resistant cholera infections.