Gut Pathogens最新文献

Background: Antimicrobial resistance, particularly in clinical Enterococcus isolates, poses a serious global health threat because of difficult-to-treat nosocomial infections. The emergence of vancomycin-resistant enterococci (VRE), mediated by VanA or VanB operons, has significantly limited treatment options. This study aimed at identifying antibiotic resistance and virulence genes in enterococci and exploring potential correlations between these genetic traits.

Methods: A total of 100 suspected enterococci were gathered from two hospitals and identified through phenotypic methods and the VITEK 2 Compact system. The Kirby-Bauer disk diffusion and MIC by microbroth dilution methods were employed for antimicrobial susceptibility. The gelatinase production and biofilm were evaluated phenotypically, while the presence of vancomycin resistance (vanA, vanB) and virulence (esp, gelE, hyl) genes was confirmed by PCR and sequenced for genetic characterization.

Results: Sixty-five Enterococcus isolates were characterized, with E. faecium (50.7%) and E. faecalis (41.5%) being the predominant species. Linezolid, teicoplanin, and chloramphenicol still retain good activity with 6.15%, 10.7%, and 29.2% resistance, respectively. About 40% of isolates were VRE, and all harbored the vanA gene. Biofilm formation and gelatinase production were most prevalent in E. faecium and E. faecalis, indicating enhanced virulence. Sequencing confirmed the chromosomal location and identity of the resistance and virulence genes, supporting their accurate detection and distribution among different Enterococcus species. Statistical analysis revealed that both esp and gelE genes were significantly associated with biofilm formation and gelatinase activity; however, esp showed a positive correlation with vanA and vancomycin resistance, while gelE demonstrated a negative correlation. Even though vanA is typically linked to high levels of resistance to both teicoplanin and vancomycin, only seven out of the twenty-six isolates that were vanA-positive showed phenotypic resistance to teicoplanin.

Conclusion: Enterococcus faecium and E. faecalis were identified as predominant multidrug-resistant species carrying multiple virulence determinants, with esp and gelE strongly linked to biofilm formation and gelatinase activity. Linezolid, teicoplanin, and chloramphenicol remained the most effective agents. Our findings demonstrate the coexistence of resistance and virulence traits, along with unexpected genotype-phenotype variations, underscoring the need for integrated molecular and phenotypic approaches in surveillance and clinical management.

Aging is a complex process marked by the gradual accumulation of impairments in molecules and tissues, leading to frailty and dysfunction. This decline is a significant risk factor for many debilitating conditions. Recently, gut microbiota dysbiosis has been identified as one of the hallmarks of aging. This review sheds light on the role of gut microbiota dysbiosis in accelerating aging and its relation to age-associated diseases, including neurodegenerative disorders, cardiovascular diseases, cancer and diabetes. Emerging research demonstrates a strong link between the gut microbiome and the aging process, although the underlying mechanisms remain under investigation. Animal studies suggest that targeting the gut microbiome may offer a promising approach to mitigate aging and related diseases. However, further human studies are needed to confirm these findings.

Blastocystis is a widespread intestinal parasite with debated pathogenicity. Blastocystis infection often persists despite metronidazole therapy, highlighting the need for adjunctive strategies. This study evaluated the therapeutic efficacy of metronidazole, Lactobacillus probiotics, and their combination against Blastocystis infection using in vitro and in vivo models. In vitro cultures of Blastocystis were treated with metronidazole (10 µg/mL), probiotics (10⁸ CFU/mL), or both. Viability and parasite counts were assessed at 24 and 48-hours post-treatment. In vivo, infected mice received metronidazole (20 mg/kg), probiotics (10⁹ CFU/day), or both for 7 days. Parasitological, histopathological, immunohistochemical, and cytokine evaluations were conducted. At 48 h in vitro, metronidazole reduced Blastocystis count by 88.6% and viability by 91.3%; probiotics reduced count by 87.2% and viability by 90.6%. The combination achieved 94.8% and 96.8% reductions, respectively (p < 0.001). In vivo, stool cysts decreased by 86% (metronidazole), 84% (probiotics), and 98.5% (combined). Intestinal cysts decreased by 85.1%, 82.9%, and 98.5%, respectively. Histological improvements and restoration of IgA-secreting cells were most prominent in the combined group. Pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ) decreased most with combination therapy-by 66.9%, 57.8%, and 60.1%, respectively-compared to untreated controls (p < 0.001). These findings indicate that probiotics enhance the efficacy of metronidazole, supporting their role as a promising adjunctive therapy for Blastocystis infection. The combined treatment yielded the most profound parasitological, immunological, and histological improvements, supporting its potential as a superior therapeutic strategy.

Background: Cryptosporidium and Microsporidia are major opportunistic pathogens in individuals with HIV, frequently causing gastrointestinal manifestations. Molecular identification of these parasites provides crucial insights into their transmission dynamics, clinical relevance, and zoonotic potential.

Methods: This cross-sectional study investigated 275 HIV-infected patients in Alborz Province, Iran (2018-2020). Stool samples were examined using Ziehl-Neelsen and modified trichrome staining, followed by PCR amplification and sequencing of the 18 S rRNA and GP60 genes for Cryptosporidium spp., and the ITS region for Enterocytozoon bieneusi and Encephalitozoon intestinalis. Associations between parasitic infections and demographic/clinical variables were analyzed using univariate and multivariable methods.

Results: Molecular analysis identified Cryptosporidium spp. in 7.6% and Microsporidia in 9.1% of patients, including E. bieneusi (6.5%), E. intestinalis (2.5%), and mixed infections (1.8%). Subtyping revealed that C. parvum (5.8%) predominantly belonged to subtype family IId (IIdA20G1, IIdA19G1), while C. hominis (1.8%) was IdA15G1. E. bieneusi genotypes D, Peru6, and J were detected-genotype J being reported for the first time in Iranian HIV-positive patients. Infections were significantly associated with clinical symptoms including chronic diarrhea, abdominal pain, vomiting, and fever. The highest rates of infection were found among patients with CD4 + counts < 200 cells/µL, no history of ART, animal contact, and use of well water.

Conclusions: This study highlights the clinical and epidemiological significance of Cryptosporidium, E. bieneusi, and E. intestinalis in HIV-infected individuals. The identification of zoonotic genotypes and their association with gastrointestinal symptoms and immunosuppression emphasizes the need for routine molecular screening, targeted public health interventions, and adoption of One Health strategies to control transmission.

Inflammatory bowel diseases (IBD) are chronic, relapsing inflammatory disorders with ulcerative colitis (UC) and Crohns disease (CD) representing the two major phenotypes. While these conditions share common features, they exhibit distinct clinical presentations, disease behaviors, and pathogenetic mechanisms, highlighting the complexity of IBD. The global incidence and prevalence of IBD have risen dramatically in recent decades, probably linked to environmental changes such as dietary habits, urbanization, and reduced microbial exposure during early life, highlighting the interplay between environmental and genetic factors in disease pathogenesis. However, genetic factors alone cannot fully explain disease onset, emphasizing the critical role of environmental and microbial influences. Dysbiosis, characterized by reduced microbial diversity, loss of beneficial commensals, and an overabundance of pathogenic taxa, has emerged as a hallmark of IBD. Recent research has increasingly focused on the functional consequences of dysbiosis, its impact on microbial metabolites and pathways that contribute to chronic inflammation and disease progression. Understanding the functional implications of multi-omics changes, rather than simply cataloguing compositional changes, is now a priority in IBD research. Using artificial intelligence to combine data from noninvasive multi-omics technologies offers a significant opportunity to explore interactions among individual omics. It could represent a shift in IBD research by showing the complex mechanisms behind disease. This approach may revolutionize diagnostics and treatments, improving the quality of life for patients through precision medicine. This review aims to provide a comprehensive assessment of current progress. It highlights critical challenges and suggests possible future directions.

Aim: Colorectal polyps serve as precursors to colorectal cancer and pose a growing public health challenge with their increasing incidence. The potential role of gut microbiota (GM) dysbiosis in colorectal polyp pathogenesis has garnered attention, yet existing evidence remains inconsistent. This study aimed to compare gut microbiota differences between colorectal polyp patients and healthy controls using systematic review and meta-analysis using 16S rRNA sequencing data.

Materials and methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search was performed across multiple databases (PubMed, Web of Science, Embase, Cochrane Library) up to April 2025. Only studies comparing gut microbiota profiles between colorectal polyp patients and healthy controls were included. Data was independently screened and extracted by two reviewers, and study quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses were conducted with R (version 4.4.1) and Stata (version 18.0), with heterogeneity assessed via the I² statistic and publication bias through funnel plots, Egger's test, Begg's test, and sensitivity analyses.Logit transformation was applied to enhance the accuracy and reproducibility of the analysis. Additionally, KEGG pathway data was utilized to explore the distinct metabolic pathway patterns between polyp patients and healthy controls.

Key findings: Systematic review and meta-analysis were performed by synthesizing 11 independent 16S rRNA-sequenced studies. Our analysis revealed that patients with colorectal polyps exhibited significantly reduced GM diversity, decreased Firmicutes abundance, and increased Fusobacteria abundance. KEGG pathway analysis indicated enrichment of the TCA cycle in polyp patients and more active amino acid metabolism in healthy controls.

Significance: Patients with colorectal polyps have distinct gut microbiota characteristics and specific metabolic shifts. These findings may facilitate the discovery of non-invasive biomarkers, guide personalized prevention strategies, and improve risk stratification for early intervention.

The gut microbiota and its hypoxic host environment play a critical role in human health. Despite its importance, the mechanisms maintaining homeostasis and the characteristics defining dysbiosis remain largely undefined. In particular, the regulation of intestinal oxygen (IO) levels emerges as a critical factor in maintaining microbial balance. Host-driven factors, including epithelial oxygen consumption, mucosal perfusion, and luminal gas diffusion, establish a hypoxic gradient essential for the stable colonization by obligate anaerobes. Disruptions to this gradient, leading to pathological hyperoxia, are associated with overgrowth of facultative anaerobic bacteria and contribute to gastrointestinal diseases like ulcerative colitis, colorectal cancer, and irritable bowel syndrome. Emerging therapeutic approaches focus on modulating IO homeostasis to address dysbiosis. Compounds like sodium tungstate inhibit microbial respiratory pathways, while PPAR-γ agonists enhance mitochondrial efficiency in colonic epithelial cells, thereby restoring proper hypoxia. Dietary interventions and probiotic therapies also hold promise by promoting local anaerobic conditions and enhancing barrier functions, thus supporting the restoration of a healthy microbial community. This review highlights the role of IO in shaping host-microbe interactions, focusing on how host IO levels influence microbial homeostasis. We evaluate the potential for IO modulation to improve gut microbiota structure and explore its impact on microbial metabolism and disease pathogenesis. Additionally, we discuss the promise of dietary, probiotic, and pharmacological interventions in restoring the host's control over the IO microenvironment and microbiota, aiming to prevent and treat related diseases.

Background: The gut microbiota plays a key role in the progression of chronic liver disease and the development of hepatocellular carcinoma (HCC). However, findings on microbiota composition in such patients remain inconsistent, likely due to differences in disease aetiology and sample type. The mucosa-associated microbiota (MAM), residing in the intestinal mucin layer, more accurately reflects mucosal health than faecal microbiota, being more stable and less influenced by diet. This study aimed to characterise the ileal and sigmoid MAM in patients with chronic hepatitis C (CHC), liver cirrhosis (LC), and HCC.

Methods: We performed DNA metabarcoding sequencing of mucosa samples collected from the ileum and sigmoid colon of patients at different stages of liver disease and healthy controls (HC). The predicted functions were analysed via phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) to infer metabolic pathways that can be expressed in the microbiome.

Results: Among 33 participants (20 HCV-related liver disease and 13 healthy controls), MAM α-diversity decreased significantly in advanced disease stages, particularly in LC and HCC, regardless of the metric applied (p ≤ 0.05). β-diversity analyses showed distinct microbial community structures across groups. Both ileal and sigmoid MAM were dominated by Bacteroidetes, Firmicutes, and Proteobacteria, with enrichment of Firmicutes_D, Proteobacteria, and Fusobacteria in LC and HCC. Several genera, including Bulleidia, Pantoea, Clostridium_Q, Rothia, and Streptococcus, were significantly increased in HCC, whereas beneficial taxa such as Akkermansia and Butyricimonas were depleted. Functional predictions indicated enrichment of degradative pathways (e.g., taurine, chitin derivatives, and carbohydrate metabolism) in LC and HCC.

Conclusion: Our pilot study suggests that MAM alterations do not directly mirror liver disease progression but show distinct patterns associated with different stages. These associations, more evident in advanced disease, involve bacterial taxa linked to gut integrity, inflammation, and carcinogenesis. This exploratory work lays the groundwork for future studies to validate these findings and investigate their relevance to microbiome-based diagnostics and therapies in HCC.

Background and aim: Recurrent spontaneous bacterial peritonitis (SBP) is a major concern for cirrhotic patients with ascites. This study seeks to identify predictors of recurrent SBP using clinical factors, inflammatory markers, and machine learning models.

Patients and methods: The study involved 347 patients with cirrhotic ascites and SBP. Receiver Operating Characteristic (ROC) curve analysis assessed the predictive ability of biomarkers. A composite score was created to evaluate the risk stratification model. Different machine learning models were compared for predictive accuracy.

Results: Eighty-three patients (23.9%) experienced recurrent SBP. Independent predictors of recurrence in multivariable analysis included acute kidney injury (AKI), elevated C-reactive protein (CRP) levels, higher serum bilirubin levels, a higher model for end-stage liver disease (MELD) score, proton-pump inhibitor (PPI) use, and lack of β-blocker use. A composite 10-point score (including AKI, CRP > 50 mg/L, low albumin levels < 2.5 g/dL, ascitic protein < 1.0 g/dL, albumin/ascitic ratio < 2.5 [2 points], MELD ≥ 15, diabetes, multidrug-resistant organism [MDRO] infection, and non-use of β-blockers) stratified the risk of recurrence into low (0-3: 15%), moderate (4-6: 45%), and high (7-10: 80%) categories. Machine learning models outperformed supervised machine logistic regression in predicting recurrence. Logistic regression achieved 70% accuracy, 65% sensitivity, and 68% specificity. The decision tree model improved accuracy to 75%, sensitivity to 72%, and specificity to 71%. The random forest model showed the best performance with 78% accuracy, 77% sensitivity, and 76% specificity.

Conclusion: A composite score, combined with machine-learning models like random forest, enhances risk assessment for SBP recurrence. Clinical predictors such as AKI, CRP, bilirubin, MELD, PPI use, and β-blockers non-use help in targeted prevention.

Background: Emerging evidence suggests a pivotal role for gut microbiota in the pathogenesis of Type 1 Diabetes (T1D). However, the compositional and functional characteristics of microbial dysbiosis in T1D remain incompletely understood. This study aimed to comprehensively characterize gut microbial alterations and associated metabolic shifts in individuals with T1D.

Methods: The present study is based on re-analysis of publicly available 16S rRNA sequencing and fecal untargeted metabolomics data from T1D patients and healthy controls generated by Yuan et al. (2022, Nature Communications). Microbial diversity was assessed using Chao1 and Fisher indices (alpha diversity), and Bray-Curtis-based Principal Coordinates Analysis (PCoA) (beta diversity). Taxonomic differences were examined at phylum, genus, and species levels, and differentially abundant taxa were identified via Linear Discriminant Analysis Effect Size (LEfSe). Correlation analyses were conducted to explore microbe-metabolite interactions.

Results: T1D individuals exhibited reduced alpha diversity and distinct beta diversity clustering compared to controls, indicating substantial shifts in microbial richness and community structure. Taxonomic analysis revealed an increased abundance of Escherichia-Shigella, Veillonella atypica, and Erysipeloclostridium ramosum in T1D, and depletion of beneficial taxa such as Bifidobacterium, Parabacteroides distasonis, Alistipes putredinis, and Bacteroides plebeius. LEfSe analysis confirmed these patterns and highlighted a T1D-specific microbial signature. Integrative correlation analysis uncovered functional dysbiosis, wherein depleted commensals were positively associated with anti-inflammatory and bioenergetic metabolites (e.g., D-gluconic acid, lactic acid, pyruvate), while T1D-enriched taxa were linked to metabolites involved in oxidative stress and immune activation.

Conclusion: Our study reveals profound structural and functional alterations in the gut microbiome of individuals with T1D. These findings support the existence of a gut microbial-metabolite axis in autoimmune diabetes and suggest that microbial biomarkers and metabolic pathways may serve as novel targets for early diagnosis and therapeutic intervention. Longitudinal studies are warranted to validate these signatures and explore microbiota-based therapies for T1D prevention and management.