Gut Pathogens最新文献

Background: A growing body of evidence suggests a relationship between gut microbiome and circulating cytokines, yet there is still a lack of large-scale population-based studies investigating gut microbiome-cytokine associations. In this cross-sectional study, we aimed at investigating the associations of gut microbiome (exposure variable) with 45 cytokines and C-reactive protein (CRP) (outcome variables) in the population-based FINRISK 2002 cohort (N = 2,398). Our analyses focused mainly on gut microbiome alpha diversity, beta diversity, differentially abundant taxa, and predicted functions. All statistical models were adjusted for age, sex, BMI, diabetes, and smoking.

Results: Using linear modeling, we identified an inverse association of the gut microbial alpha diversity (Shannon index) with CRP (β=-0.062 ± 0.019/standard deviation (SD), False Discovery Rate adjusted p-value (FDR-P) = 0.025), interleukin-8 (IL-8) (β=-0.066 ± 0.021/SD, FDR-P = 0.025), and interferon-γ-inducible protein 10 (IP-10) (β=-0.063 ± 0.02/SD, FDR-P = 0.025). For beta diversity, linear modeling revealed that the first axis of Principal Component Analysis (PCA) describing the most strongly varying parts of the microbial community composition across population was inversely associated with CRP (β=-0.071 ± 0.019/SD, FDR-P = 0.008) and the second axis was inversely associated with macrophage inflammatory protein-1β (MIP-1B) (β=-0.082 ± 0.021/SD, FDR-P = 0.008), and monokine induced by interferon-γ (MIG) (β=-0.071 ± 0.019/SD, FDR-P = 0.008). The majority of the top taxa contributing to the first and second PCA axes belonged to class Bacilli (7/10) and class Gammaproteobacteria (9/10), respectively. In addition to this, we detected 8 significant associations of specific gut microbiome taxa (species-level) with cytokines and CRP using linear models. The majority of significant taxa belonged to class Clostridia_258483 (5/8) and class Bacteroidia (2/8). We did not detect any significant associations between species-specific predicted MetaCyc pathways (using all prevalent pathways) and cytokines or CRP. When analysis was limited to pathways associated with significant species only, we observed a positive association between purine synthesis predicted pathways in B. thetaiotaomicron and CRP.

Conclusions: Taken together, these results show that CRP, MIP-1B, IL-8, and other cytokines are associated with gut microbial diversity and composition, as well as specific taxa. This could lay the groundwork for future experimental studies to assess the causality of these associations.

Background: Carbapenem-resistant Escherichia coli (CREC) can cause persistent or multi-site infections, leading to significant clinical challenges due to the limited availability of effective antibiotics. However, the within-host evolution of CREC and its impact on infection patterns remain poorly understood. This study aims to characterize CREC isolates from patients with recurrent or multi-site infections to elucidate the relationship between bacterial adaptation within the host and infection dynamics, thereby addressing a critical gap in our understanding of CREC pathogenesis.

Results: Genotypic analysis, including Nanopore whole-genome sequencing, and phenotypic comparisons were performed on CREC isolates from individual patients. Pulsed-field gel electrophoresis (PFGE) patterns revealed that 18 patients were consistently infected with highly genetically related strains. Moreover, two patients (Patients 16 and 18) experienced sequential infections caused by genetically distinct strains, resulting in a total of 20 strain groups. Among these, seven (35%) belonged to phylogroup B1, six (30%) to phylogroup A, four (20%) to phylogroup B2, and three (15%) to phylogroup D. Nine groups were multidrug-resistant (MDR), six were extensively drug-resistant (XDR), and four shifted from XDR to MDR. Notably, group 18 - 1 included two MDR and five XDR strains. We examined the distribution of 31 virulence-associated genes across 20 groups and found that only three groups carried less than 10 genes. However, all strains within the same group harbored the same set of virulence genes. Larvae infection models revealed that strains from patients 7 and 8 became increasingly virulent over time, while those from patients 11 and 16 showed reduced virulence. Plaque assays revealed variability in phage susceptibility among isolates from different patients, as well as among consecutive isolates obtained from the same patient over time. Whole-genome sequencing results suggested plasmid dissemination among CREC strains in patients 5 and 18 based on highly identical plasmid sequences.

Conclusions: These findings underscore the significance of bacterial genomic changes and plasmid transfer in driving phenotypic evolution, enabling CREC to adapt and persist within hosts under selective pressures, thereby sustaining infections.

Background: The real-world comparative effectiveness study aimed to compare the effectiveness of vonoprazan (VON)-based therapy with high-dose esomeprazole (ESO)-based therapy in the re-eradication of Helicobacter pylori.

Methods: This real-world retrospective study analyzed patients at Nanjing First Hospital undergoing H. pylori re-eradication, who received either vonoprazan-based (VON) or high-dose esomeprazole-based (ESO) quadruple therapy. Both regimens included amoxicillin, furazolidone, and bismuth, administered twice daily for 14 days. Treatment strategies were determined by routine clinical practice, using either culture results or local epidemiological data. Patients were further classified into individualized precision (VON-P, ESO-P) or empirical (VON-E, ESO-E) groups based on real-world clinical decision-making.

Results: The H. pylori re-eradication rates were 89.2% (191/214, 95% CI: 84.4-92.7%) in group ESO and 86.0% (98/114, 95% CI: 78.4-91.2%) in group VON, with no statistically significant difference between groups (P = 0.381). Among patients receiving individualized precision treatment, the re-eradication rates were 87.3% (62/71, 95%CI: 77.6-93.2%) for group ESO-P and 86.9% (53/61, 95% CI: 76.2-93.2%) for group VON-P, with no significant difference observed (P = 0.940). Similarly, for patients undergoing empirical treatment, there was no statistically significant difference in re-eradication rates between group ESO-E and group VON-E (90.2%, 129/143, 95% CI: 84.2-94.1% vs. 84.9%, 45/53, 95% CI: 72.9-92.1%; P = 0.296). Additionally, no significant difference was found between group ESO-E and group ESO-P (90.2%, 129/143, 95% CI: 84.2-94.1% vs. 87.3%, 62/71, 95% CI: 77.6-93.2%; P = 0.521), nor between group VON-E and group VON-P (84.9%, 45/53, 95% CI: 72.9-92.1% vs. 86.9%, 53/61, 76.2-93.2%; P = 0.762).

Conclusions: Both high-dose esomeprazole-containing quadruple therapy and VON-containing quadruple therapy have demonstrated effective as rescue treatments for H. pylori infection. Additionally, antibiotic selection informed by local epidemiological data demonstrated comparable effective to culture-based methods in this cohort, though future large-scale studies are needed to validate its generalizability.

Background: Lactobacillus reuteri DSM 17,938 exhibits antidepressant and anxiolytic potential. The purpose of this study is to validate the effects of L. reuteri DSM 17,938 and preliminarily explore its underlying antidepressant and anxiolytic mechanisms, thereby providing a general direction for researching the targets of its antidepressant and anxiolytic effects.

Methods: The depressive mouse model induced by lipopolysaccharide (LPS) was intervened with L. reuteri DSM 17,938 (5 × 10⁹ cfu/ml), and behavioral experiments were conducted to evaluate the therapeutic effects of the probiotic on depression. Moreover, the antidepressant and anxiolytic mechanism of probiotics was investigated through fecal metagenomics and fecal non-targeted metabolomics, as well as non-targeted metabolomics of the hippocampus and prefrontal cortex.

Results: In the behavioral experiments, L. reuteri DSM 17,938 significantly reversed the phenomena of reduced total moving distance, decreased center zone stay time and increased peripheral zone stay time in the open field test of LPS-induced depressed mice, and significantly reduced the immobility time of mice in the forced swimming test. L. reuteri DSM 17,938 restored gut microbial richness and ameliorated intestinal metabolic pathways in a depression mouse model, with lipopolysaccharide biosynthesis and ATP-binding cassette transporter (ABC) transporter metabolic pathways being significantly enriched. Untargeted metabolomics of the hippocampus and prefrontal cortex revealed that LPS intervention primarily induced dysregulation of amino acid metabolism-related pathways in these brain regions. In contrast, L. reuteri DSM 17,938 administration restored neural homeostasis, as evidenced by KEGG functional enrichment analysis identifying activated amino acid metabolism and unsaturated fatty acid metabolism pathways.

Conclusion: These findings collectively suggest that L. reuteri DSM 17,938 exerts antidepressant and anxiolytic effects by modulating gut microbiota composition to improve intestinal metabolism and subsequently rectifying amino acid and unsaturated fatty acid metabolic pathways in the hippocampus and prefrontal cortex. This study elucidate the gut-brain axis mechanisms underlying its antidepressant and anxiolytic effect and highlight its potential as a novel probiotic-based strategy for mood disorders.

Background: Symbiotic microbes benefit the host, but the emergence of pathobionts leads to disease. An invasive Escherichia coli LI60C3, isolated from mouse colonocytes, shows colitogenic and tumorigenic properties. Despite extensive research on the role of microbiota in colorectal cancer (CRC) development, the genetic markers associated with this pathobiont remain elusive. The objective is to characterize the tumorigenic E. coli through whole-genome sequencing (WGS) and phenotypic assays, and validate their presence in human CRC.

Methods: The intracellular bacterial counts and proliferation rates of human intestinal epithelial cells were evaluated after exposure to various E. coli strains. Tumor burden was assessed in mice orally administered LI60C3. WGS of LI60C3 was performed on a PacBio Sequel II platform, and the long reads were assembled de novo for gene annotation and detection of virulence factors and antibiotic resistance. Bacteria-specific genes were assessed in CRC specimens by qPCR analysis.

Results: A 100-fold increase in intracellular bacterial count was observed in epithelial cells exposed to LI60C3 compared to commensal E. coli strains. LI60C3 resulted in a threefold increase in epithelial cell cycle rate and a fourfold rise in mouse tumor numbers. WGS revealed a circular chromosome of 4,863,930 bases for LI60C3, demonstrating a high sequence homology to adherent-invasive E. coli LF82 (91%) and NC101 (87%) and to uropathogenic E. coli 536 (88%). Two extrachromosomal plasmids, pTra and pCoMb, were identified. While pTra exhibits sequence homology with other commensal E. coli plasmids, pCoMb has partial matches with those found in pathogenic bacteria. LI60C3 is classified as phylogroup B2 and expresses virulence factors, including Type 1 and P fimbriae, contact-dependent growth inhibition system, iron acquisition system, and hemolysin. Unique gene clusters, named Epm and Phz islands, were identified in the LI60C3 genome. The emergence of LI60C3-specific genes was observed in mouse tumors induced by chemicals and gene mutation, and higher levels of LI60C3 markers were validated in human CRC specimens compared with healthy mucosal samples.

Conclusion: Genetic signatures of LI60C3 were detected in mouse and human CRC. The comparative genome analysis for LI60C3 helps identify pathobionts and may be used as cancer predictors.

Background: Colorectal cancer (CRC) is a prevalent global malignancy where gut microbiota plays a key role. Streptococcus gallolyticus (Sg), a gut commensal and opportunistic pathogen, is associated with CRC. This study investigates the impact of the supernatant derived from Sg cultures (hereafter referred to as Sgsup) on CRC progression and examines the underlying mechanisms.

Methods: Quantitative PCR (qPCR) was employed to assess Sg colonization in paired tumors and adjacent normal tissues from 46 CRC patients. CRC cell lines (HCT116, HT29) were treated with Sgsup, and cell proliferation was measured using the CCK-8 assay. Non-targeted metabolomic profiling of Sgsup was performed via liquid chromatography-mass spectrometry (LC-MS). An azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse model of CRC was used to evaluate in vivo tumor burden, inflammation, and macrophage polarization (flow cytometry). Transcriptomic analysis via RNA-seq was conducted to identify enriched signaling pathways.

Results: The detection rate of Sg was significantly higher in tumor tissues compared to adjacent tissues (47.8% vs. 30.4%, P < 0.01). Sgsup significantly increased CRC cell proliferation (P < 0.05). Non-targeted metabolomic analysis revealed an enrichment of metabolites, including inosine monophosphate (IMP), methionine, uridine, and creatine in Sgsup. In vivo, Sgsup increased tumor number/burden (P < 0.05), elevated inflammation scores (P < 0.05), and shortened colon length. Flow cytometry indicated that Sgsup promoted M2 macrophage polarization (as evidenced by increased CD206⁺ cells and reduced M1/M2 ratio). RNA-seq demonstrated significant enrichment of the IL-17 signaling pathway, with upregulated expression of IL-17 F and IL-22 (P < 0.05).

Conclusion: Sgsup is associated with CRC progression by promoting cell proliferation and inflammation, facilitating M2 macrophage polarization, and elevating IL-17 F and IL-22 expression. Metabolites such as creatine, along with IL-17 F/IL-22-related signaling pathways, appear to be involved. These findings suggest that both Sg-derived metabolites and host immune signaling may serve as potential targets for CRC intervention. Functional validation of individual metabolites is currently in progress.

Emerging evidence suggests the link between pulmonary tuberculosis (PTB) and gut microbiota dysbiosis. This is the first study from the southern Indian population that characterized the gut microbiota of PTB patients using 16 S amplicon sequencing. The analysis revealed a significant reduction in gut microbial diversity among PTB patients, with particularly lower alpha diversity (Chao1 index, p ≤ 0.0001) than healthy controls (HC). This was further depleted during antitubercular therapy (ATT). Beta diversity indicated distinct clustering in all the groups (p < 0.05). Subgroup analyses showed that supplementation of probiotics with ATT improved microbial richness and diversity. However, broader shifts in composition were not observed. At the genus level, specific taxa were upregulated or downregulated in PTB patients compared to HC. Functional analysis showed a depletion in biosynthesis pathways in PTB patients. Short-term probiotic supplementation had a partial effect on microbial recovery but did not fully restore gut microbial diversity. These findings highlight persistent dysbiosis in PTB patients, even after ATT. Large-scale studies are needed to evaluate the role of microbiome-targeted therapies to address this dysbiosis.

Aim: Blastocystis spp. is a common intestinal protozoan with controversial pathogenicity. It is frequently associated with gastrointestinal (GIT) disturbances and is particularly prevalent among immunocompromised individuals. This study aimed to assess the prevalence of Blastocystis spp. infection and its association with immunological and hematological parameters among chronic leukemic patients.

Methods: Stool and blood samples were collected from 100 chronic leukemic patients. Microscopic examination and a coproantigen assay were performed for the detection of Blastocystis spp., along with assessment of anti-Blastocystis fecal IgA and serum IgG antibodies. CD4 T cells and the serum level of IL-8 were also measured.

Results: The overall Blastocystis spp. infection rate was 60%, determined through combined microscopy and/or coproantigen detection. Among infected patients, anti-Blastocystis IgA was positive in only three patients and IgG in 18 patients, with no statistically significant association between Blastocystis spp. infection and detection of antibodies. Infection was significantly associated with elevated IL-8 levels and WBC count. There was no statistically significant association between the presence of gastrointestinal symptoms and the levels of anti-Blastocystis IgG or IgA, IL-8, or CD4 count in Blastocystis spp.-infected patients.

Conclusion: Our study reveals a high prevalence of Blastocystis spp. infection among chronic leukemic patients and identifies a significant association between infection and elevated IL-8 levels.