Gut Pathogens最新文献

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.

Ulcerative Colitis (UC) is a chronic illness that commonly demands the use of medication, sometimes for long term. In a DSS mouse model, we examined 5-aminosalicylic acid (5ASA) in comparison to a defined polyphenol-rich herbal mixture CSPG: Cirsium japonicum, Scutellaria baicalensis, Paeonia japonica, and Glycyrrhizae radix, using a two-phase approach. In phase 1 (days 1-14, without DSS stimulation), the herbal formula CSPG produced a more gut-friendly preventive profile compared to 5ASA in non-inflammatory condition:Unlike 5-ASA, which decreases microbial diversity as previously reported, CSPG preserved overall diversity and maintained protective taxa such as Ruminococcaceae uncultured ; and reduced inflammatory metabolites (uracil, glyceric acid, succinic acid) more effectively than 5ASA. Next, in phase 2 (days 15-24, with DSS inflammatory stimulation), CSPG matched first-line 5-ASA in suppressing inflammation (reduced colon shortening and procalcitonin). Its PI3K-Akt upregulation-together with NF-κB repression-was associated with more continuous ZO-1/ZO-2/occludin proteins expression and normalization of claudin-2 and MUC1/MUC2/MUC4, indicating barrier-repair capacity, a result supported by in vitro HT-29 experiments. Simultaneously, CSPG corrected DSS-induced dysbiosis more effectively than 5ASA: it increased SCFA-linked taxa (Prevotellaceae UCG-001 and Ruminococcus; 5ASA also rose but to a lesser extent), and reduced inflammation-associated groups ( [Eubacterium] siraeum group, and Erysipelotrichaceae). CSPG restored SCFAs and elevated glycine, proline, pyruvate, and myo-inositol, while reducing succinate and uracil-with stronger effects than 5-ASA for pyruvate, myo-inositol, and succinate, and comparable effects for butyrate. Although CSPG is not a single-target, rationally designed drug like 5ASA, it achieved comparable anti-inflammatory and barrier-repair effects and, unlike 5ASA, also improved gut microbiota composition and metabolite profiles, indicating potential advantages for long-term UC management.

Background: Brevilin A (Br) has shown potential in modulating inflammatory bowel disease (IBD). Our study aims to explore its mechanism of anti-inflammatory action.

Methods: Colitis was induced in C57BL/6 mice with dextran sulfate sodium (DSS), followed by treatment with or without Br(20 mg/kg). Fecal microbiota and metabolites were profiled by metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS), respectively. Furthermore, to delineate the essential role of the gut microbiota, we employed antibiotic-treated (microbiota-depleted) mice in our investigation of Br's mechanism of action.

Results: Br significantly alleviated DSS-induced colitis and modulated the gut microbiota profile. Specifically, Br enriched beneficial bacteria such as Lactobacillus, while suppressing pathogenic bacteria including Escherichia coli and Clostridium perfringens. Metabolomic analysis revealed that Br significantly altered bacterial metabolites, including 7-Oxolithocholic Acid, Kudinoside A, Veratrine, and Soyasaponin. These metabolites were linked to key pathways such as GPCR signaling, DNA damage response, aminoacyl-tRNA biosynthesis, riboflavin metabolism, and central carbon metabolism in cancer. Transcriptomic profiling indicated that Br inhibited the TNF-α signaling pathway, and this inhibition was confirmed as TNF-α overexpression reversed its anti-inflammatory effects. Furthermore, the therapeutic effects of Br were partially recapitulated in microbiota-depleted mice through fecal microbiota transplantation from Br-treated donors.

Conclusion: Br's ability to regulate gut microbiota and metabolites, improve gut barrier function, and eliminate inflammation by inhibiting TNF-α highlights its potential as a novel therapeutic medicine for IBD. Future research should focus on further exploring its mechanisms and clinical applications.

Background: Critical illness often leads to the development of intestinal dysbiosis, which can have a significant impact on disease outcome. Intestinal barrier dysfunction is a common problem in intensive care unit patients, particularly those with sepsis. Despite its importance, early and reliable diagnosis of barrier dysfunction and evaluation of therapeutic options remain lacking in clinical practice. Given that intestinal hyperpermeability is associated with increased translocation of luminal antigens and subsequent priming of naïve T cells, we hypothesized that analysis of circulating peripheral antigen-reactive T cells could provide insight into the functionality of the intestinal barrier.

Results: To test this hypothesis, 70 ICU patients were enrolled, including those with sepsis, those not meeting sepsis criteria, and COVID-19 patients, as well as 20 healthy volunteers. We identified a sepsis-specific T-helper cell signature in peripheral blood using the antigen-reactive T-cell enrichment (ARTE) technique followed by flow cytometric analysis. This signature was characterized by an expansion of gut trophic Bifidobacterium longum-reactive T-helper cells, indicating significant intestinal barrier dysfunction during sepsis.

Conclusion: This approach allows the study of intestinal barrier functionality and provides a means to monitor the effects of potential therapeutic interventions over time using blood samples.

Background: Biologic therapy has improved outcomes in inflammatory bowel disease (IBD) but may predispose patients to enteric opportunistic infections. Asian data comparing infection risk across biologic classes remain scarce. We therefore assessed the incidence of Clostridioides difficile infection (CDI), Clostridium innocuum (CI) infection, and cytomegalovirus (CMV) colitis in IBD patients treated with Vedolizumab (VDZ), anti-tumor necrosis factor agents (anti-TNF), or Ustekinumab (UST).

Methods: This single‑center, retrospective cohort study included IBD patients who initiated VDZ, anti‑TNF (infliximab or adalimumab) or UST at Chang Gung IBD Center between January 2017 and December 2024. Opportunistic infection was defined as: (i) toxin‑gene PCR-positive CDI, (ii) CI isolated in stool/colonic culture, or (iii) CMV‑positive immunohistochemistry on intestinal biopsy. Incidence rates were expressed per 100 patient‑years. Infection‑free survival was compared with Kaplan-Meier analysis and log‑rank testing. Multivariable logistic regression identified independent predictors of CDI.

Results: A total of 614 patients (377 Crohn's disease; 237 ulcerative colitis) contributed 941 patient‑years of follow‑up. The incidences per 100 patient-years were 3.51 for CDI, 0.85 for CI, and 3.30 for CMV colitis. CDI and CI risks were comparable across VDZ, anti‑TNF and UST cohorts. CMV colitis was significantly more common with anti‑TNF therapy (5.9%) than with VDZ (3.4%) or UST (0.5%) (p = 0.020). Independent predictors of CDI were an acute IBD flare (odds ratio [OR] 3.64; 95% confidence interval 1.91-6.91), concurrent CMV colitis (OR 6.34; 95% confidence interval 2.03-19.8) and CI infection (OR 7.79; 95% confidence interval 1.40-43.3).

Conclusion: VDZ and UST were not associated with excess CDI, CI or CMV risk, whereas anti‑TNF therapy conferred a higher burden of CMV colitis. Heightened infection surveillance is warranted during acute flares and refractory disease courses.

Aliarcobacter spp. bacteria are human enteropathogens, as are Campylobacter spp. However, the epidemiology of the former infections is not well described. Here, we present microbiological and clinical data on 1,204 Aliarcobacter spp. infections that occurred in France between 2002 and 2024. Aliarcobacter butzleri was the principal species identified, followed by A. cryaerophilus. Aliarcobacter spp. infections affected patients principally over 60 years of age, mostly men, particularly during autumn. Analysis of 253 clinical information sheets highlighted both diarrhea and abdominal pain that were only rarely associated with fever or blood in the stool. Many isolates of both main species were resistant to group A penicillins and ciprofloxacin.

Background: Alterations in the gut microbiome via the gut-liver axis are closely linked to metabolic dysfunction-associated steatotic liver disease (MASLD) and may contribute to hepatocellular carcinoma (HCC) development. However, the interplay between the gut microbiome and host gene expression in MASLD and HCC remains poorly understood.

Methods: We analyzed the gut microbiome from fecal samples and host transcriptomic profiles from peripheral blood mononuclear cells (PBMCs) in healthy controls and MASLD patients without HCC (mild fibrosis F01 and significant fibrosis F234) and with HCC.

Results: Integrated analysis identified 260 differentially expressed genes (DEGs) and 29 bacterial taxa differentiating MASLD without HCC from MASLD-HCC. Subgroup analysis revealed seven bacterial genera associated with 84 host genes. Notably, Veillonella correlated with regulating synaptic membrane exocytosis 3 (RIMS3), collagen type X alpha 1 (COL10A1), and enabled homolog (ENAH). Real-time PCR validation confirmed COL10A1 as a significant diagnostic biomarker for distinguishing MASLD from MASLD-HCC (AUC = 0.835). Combining COL10A1, and AFP, or Veillonella with AFP, significantly improved differentiation between MASLD and MASLD-HCC, particularly in early-stage fibrosis (F01) (AUC = 0.941 and 0.996, respectively).

Conclusions: Gut microbiome-host gene interactions appear to play a significant role in MASLD-related HCC progression. Specific bacterial genera and host gene expression profiles may serve as early diagnostic markers for MASLD-HCC.