Gut Pathogens最新文献

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with mounting evidence implicating the gut microbiome in its pathogenesis. Among the microbial agents, Fusobacterium nucleatum has emerged as a prominent contributor, frequently detected in CRC tissues and associated with advanced disease stages and poor prognosis. This review highlights the complex interplay between F. nucleatum and host non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in modulating CRC biology. F. nucleatum influences the expression of several ncRNAs, which in turn regulate key signaling pathways such as Wnt/β-catenin (e.g., miR-1246, miR-135b), PI3K/AKT (e.g., miR-22, miR-135b), and TLR4/NF-κB (e.g., miR-31, lnc-NEAT1). Through these mechanisms, F. nucleatum contributes to tumor cell proliferation, immune evasion, metastasis, and chemoresistance. Additionally, its impact on ncRNA expression is implicated in reduced efficacy of standard chemotherapy. Emerging microbiota-based therapies, including probiotics and fecal microbiota transplantation, show promise in modulating gut flora and potentially reversing ncRNA dysregulation; however, their mechanistic effects on the F. nucleatum-ncRNA axis require further investigation. This review underscores the critical role of F. nucleatum-regulated ncRNAs in CRC and presents new opportunities for biomarker discovery and targeted therapeutics.

Background: Salmonella typhimurium (S. typhimurium) is one of the typical intestinal pathogens leading to gastrointestinal diseases. Circular RNA (circRNA) is a covalently closed-loop RNA molecule that lacks 3' and 5' ends, and it plays a crucial role in the pathogenesis and progression of human diseases. However, whether host circRNAs expression could be regulated by S. typhimurium infection during tumorigenesis and development is still not clear. This study aim is to explore the therapeutic potential and underlying mechanisms of altered circular RNAs expression in S. typhimurium infection in colorectal cancer (CRC).

Results: Transcriptomic analysis revealed numerous cellular circRNAs that were significantly regulated by S. typhimurium in the colorectal cancer cell line HCT116. Notably, circHIPK2 exhibited the most pronounced downregulation among them. Knockdown of circHIPK2 inhibited cell motility, tumor growth and epithelial cell cytokine expression like IL8, IL6 and GM-CSF induced by SL1344. The interaction between circHIPK2 with miR-124-3p was confirmed through RNA molecular binding experiment. Furthermore, overexpressed miR-124-3p abrogated cell motility induced by circHIPK2.

Conclusion: The S. typhimurium-regulated circHIPK2/miR-124-3p axis is pivotal in CRC pathogenesis and holds promise as a molecular therapeutic target for treating colitis-associated colorectal cancer.

Background: Norovirus is the predominant pathogen responsible for global acute gastroenteritis outbreaks and sporadic cases. While GII.3[P12] norovirus is typically associated with sporadic cases of acute gastroenteritis, outbreaks caused by this genotype increased sharply in Beijing from 2021 to 2023. This study aimed to characterize the GII.3[P12] norovirus outbreaks in Beijing from August 2021 to July 2023, analyze whole-genome sequences, and infer spread dynamics.

Results: GII.3[P12] outbreaks primarily occurred in winter and spring (90.68%, 107/118), concentrated in urban areas (56.78%, 67/118). Ninety-three outbreaks (78.81%, 93/118) were reported in kindergartens. Person-to-person transmission was the main route, accounting for 99.14% (115/116) of outbreaks with a defined route. The maximum clade credibility tree, constructed from partial viral capsid protein 1 and RNA-dependent RNA polymerase genes, showed that GII.3[P12] strains are clustered into three clades, aligning with analyses of 82 whole-genome sequences. Bayesian inference revealed that the most recent ancestor for the three clades of the maximum clade credibility tree based on whole-genome sequences was 2015.66, 2016.56, and 2017.71, respectively, and urban areas are key transmission hubs. The histo-blood group antigens binding sites were conserved, and there were some unique amino acid mutations in the open reading frame 1 region: clade 1 (V779I/D870G/K1004R/I1057V/I1521V), clade 2 (A21V/S195L/R278K/V779I/A782V/A791V/I850T/P1051S/V1091A/S1571T), and clade 3 (T701I).

Conclusions: Our study identified GII.3[P12] as the dominant strain in norovirus outbreaks in Beijing, China (2021-2023). We obtained 82 whole-genome sequences via next-generation sequencing, revealing amino acid mutation-driven evolution, inferring local transmission dynamics, and providing insights for outbreak control and vaccine development.

Candida albicans is an opportunistic pathogen that resides in the human gut alongside a diverse array of microorganisms, including enteric bacteria, archaea, and viruses, which collectively form the gut microbiota. Recent studies have shown that the development of Candida albicans infections involves both weakened host immunity and enhanced invasiveness of Candida albicans, with intestinal microecology serving as a critical mediator of these processes. It has been demonstrated that disturbances in the gut microbiome can potentiate the invasive capacity of Candida albicans. Moreover, a compromised immune system, along with the use of antibiotics and immunosuppressive drugs, can lead to gut microbiome imbalances. Consequently, modulators of the intestinal microecology represent promising therapeutic interventions for managing Candida albicans infections. In this review, we examine the mechanisms underlying the increased invasiveness of Candida albicans following significant disruption of intestinal bacteria and highlighting the interplay among immune dysfunction, antibiotic use, and their effects on gut microbiome imbalance and Candida albicans infection. Additionally, we summarize the roles of microbiome-based therapies, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), in addressing Candida albicans infections. This review provides a theoretical foundation and practical guidance for the development of more effective microecological therapeutic strategies in the future.

Background: Helicobacter pylori infection, commonly observed in peptic ulcers, induces chronic systemic inflammation. Chronic obstructive pulmonary disease (COPD) and asthma are inflammatory airway diseases. We investigated the association of H. pylori infection with COPD and asthma.

Methods: Data from individuals who underwent H. pylori eradication treatment between 2009 and 2017 were obtained from the Korean National Health Insurance Database. In total, 33,017 individuals aged ≥ 40 years with H. pylori infection and 168,524 matched controls were identified and monitored until December 2019. Multivariate Cox proportional hazards models were used to estimate the adjusted hazard ratios (aHR) for risk factors associated with COPD and asthma.

Results: The incidences of COPD and asthma among individuals with H. pylori infection were 10.92/1,000 person-years and 15.99/1,000 person-years, respectively. The risk of developing COPD (aHR 1.13, 95% confidence interval [CI] 1.08-1.19) and asthma (aHR 1.17, 95% CI 1.12-1.22) was higher among individuals with H. pylori infection, even after adjusting for smoking status. Subgroup analysis revealed that the risk of COPD was more pronounced among older adults (≥ 65 years) and current smokers. In contrast, the risk for asthma did not differ according to age or smoking status.

Conclusions: H. pylori infection is associated with an increased risk of COPD and asthma. The risk of asthma was consistent across age groups and smoking statuses; in contrast, the risk of COPD varied. The findings of the present study underscore the pathophysiological interactions between chronic inflammation in the stomach and the lungs.

Background: There is increasing evidence suggesting that the gut microbiota plays a key role in the development of insulin resistance (IR). Therefore, the present bibliometric study aimed to characterize the development trends and research hotspots of publications related to the gut microbiota and IR.

Methods: Publications on the gut microbiota and IR between 2015 and 2024 were retrieved from the Scopus database. Bibliometric analyses were conducted with the VOSviewer version 1.6.20 software program.

Results: The Scopus query (15 June 2025) retrieved 584 publications on the gut microbiota and IR. Most were research articles (n = 480, 82.19%), followed by reviews (n = 82, 14.04%). Output is highly skewed toward East Asia and North America, with China leading the list with 254 papers (43.49%), followed by the United States (96; 16.44%), Canada (44; 7.53%), and Germany (27; 4.62%). Term-cooccurrence mapping in VOSviewer (v1.6.20) of the 251 high-frequency keywords (≥ 15 occurrences) resolved three thematic clusters: Cluster 1 focused on the high-fat-diet gut-liver axis; Cluster 2 examined patient-centered epidemiology and clinical trials; and Cluster 3 investigated inflammatory and metabolic signalling.

Conclusions: The annual number of publications on the gut microbiota and IR has increased rapidly in the past ten years, demonstrating that the gut microbiota and IR have the potential to be researched precisely and are attracting increasing attention. The findings of this study can help researchers explore new directions for future research in this area and could serve as a reference for future academic research.

The evolution of colorectal cancer (CRC) follows a progression from polyp to adenoma and eventually to cancer. The implementation of CRC screening is an effective strategy to interrupt the disease process and reduce morbidity and mortality during this process. Early diagnosis and treatment of tumors can be facilitated through widespread screening campaigns, thereby reducing the economic burden on the state, society and families. In order to achieve this goal, the key lies in the development of screening methods that are both efficient and economical to ensure that they can be widely disseminated and minimize the rate of missed diagnoses. At home and abroad, numerous scholars and experts have devoted themselves to the study of CRC screening methods. This review synthesizes current evidence through a systematic literature review to evaluate existing CRC screening methodologies, thereby offering critical insights to inform clinical decision-making in optimizing screening strategy selection.

Background: The availability of a broadly protective vaccine against pathogenic Escherichia coli could help to reduce morbidity and mortality from severe gastrointestinal and systemic infections. E. coli vaccine development efforts often target protein virulence factors that natively are extensively glycosylated, but this glycosylation is absent from recombinantly produced vaccine antigens. Human IgA responses to the conserved virulence factor YghJ have recently been shown to frequently target glycosylated epitopes. Here we evaluated to what extent anti-YghJ IgG responses also target glycosylated epitopes, longevity of these responses, and to what extent the responses correlated with the IgA responses.

Methods: Multiplex bead flow cytometric immunoassays were used to evaluate changes in anti-YghJ IgG levels and glycosylation specificity in serum and antibody in lymphocyte supernatant (ALS) collected from 21 volunteers experimentally infected with enterotoxigenic E. coli (ETEC) strain TW10722.

Results: Following infection, most volunteers had substantially increased anti-YghJ IgG levels both in serum and ALS. The proportion of serum anti-YghJ IgG that specifically targeted glycosylated epitopes increased from 0.10 (Interquartile range [IQR]: 0.07, 0.21) before to 0.17 (IQR: 0.11, 0.38) 10 days after dose ingestion before returning to pre-infection levels after 28 days. The glycosylation-specific proportions correlated between IgG and IgA for both serum and ALS.

Conclusion: Our findings indicate that glycosylated epitopes are an important target for antibody immune responses and may play an important role in host immunity during the early phase of infection.

Background: The growing resistance of Helicobacter pylori (H. pylori) to antibiotics poses a significant global health challenge, particularly in developing regions where infection rates are high, and routine antibiotic susceptibility surveillance is limited. This study aimed to evaluate the antimicrobial resistance patterns and associated genetic mutations in H. pylori strains isolated from patients in West Bengal (WB), India.

Methods: A total of 88 H. pylori strains were isolated from gastric biopsy samples collected between 2018 and 2020 from patients diagnosed with gastritis, duodenal ulcer, or gastric cancer. Antimicrobial susceptibility was determined using the agar dilution method against six antibiotics: metronidazole, tetracycline, clarithromycin, furazolidone, levofloxacin, and amoxicillin. Resistance-associated mutations in gyrA (levofloxacin), frxA and rdxA (metronidazole), and pbp1A (amoxicillin) were characterized via Sanger sequencing. Mutations in the 23SrRNA gene, implicated in clarithromycin resistance, were identified through allele-specific PCR, validated by Sanger sequencing and transformation assays. Additionally, BsaI and BbsI restriction enzyme digestion was used to confirm specific point mutations in 23SrRNA gene of clarithromycin-resistant isolates.

Results: Of 210 biopsies analyzed, 79 (37.6%) were H. pylori-positive, yielding 88 distinct strains-some patients harbored multiple genetically diverse isolates, identified by differences in cagA/vacA genotypes and antibiotic resistance profiles. Although, no association was found between virulence gene profile and resistance pattern. Resistance rates were highest for levofloxacin (69.3%), followed by metronidazole (61.4%) and clarithromycin (19.3%). Nearly all clarithromycin-resistant isolates carried the A2143G mutation in the 23SrRNA gene, capable of getting naturally transmitted into the next generations also. Levofloxacin-resistant strains harbored mutations in GyrA at codons 63, 87, 88, 91, 130, and 150, and a novel Gly85Ala substitution was identified. Metronidazole resistance correlated more strongly with rdxA mutations than with frxA. No resistance was detected against furazolidone and tetracycline, while amoxicillin resistance was rare (1.1%). Multidrug resistance was observed in 10.2% of isolates, with 32.9% displaying dual resistance to metronidazole + levofloxacin, and 6.8% to clarithromycin + levofloxacin.

Conclusions: High clarithromycin, substantial metronidazole and levofloxacin resistance in H. pylori strains from WB underscore the urgent need to revise empirical treatment strategies. These findings advocate for localized, resistance-guided therapy protocols and reinforce the importance of continuous antimicrobial surveillance to optimize treatment outcomes and mitigate resistance development.