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BackgroundNumerous studies have highlighted the close association between gut microbiota and the development of ulcerative colitis (UC), yet research on whether immune cells mediate this process remains scarce. This study utilizes various Mendelian randomization (MR) methods to investigate the causal relationship between gut microbiota and UC, further exploring the mediating role of immune cells in this process.MethodsGenome-wide association study (GWAS) summary statistics for 473 gut microbiota, 731 immune cell phenotypes, and UC were obtained from the GWAS catalog database. Single nucleotide polymorphisms (SNP) were used as instrumental variables (IV) to validate the causal relationship between gut microbiota and UC through two-sample MR and Bayesian weighted MR (BWMR), and reverse MR was employed to explore the presence of reverse causal effects. Two-step MR was applied to identify immune cell mediators and evaluate their mediation effects.ResultsThe study revealed a causal relationship between 20 gut microbiota and UC, with 14 microbiota acting as protective factors for UC and 6 as risk factors. Mediation MR identified 26 immune cell mediators, among which the association between CD11b on Mo MDSC and Bifidobacterium bifidum (B. bifidum) was most significant (p = 0.0017, OR = 1.4540, 95% CI: 1.1504–1.8378). Mediation MR analysis indicated that the mediation effect of CD11b on Mo MDSC between B. bifidum and UC was −0.0385, with a mediation effect ratio of 16.67%.ConclusionThere is a clear causal relationship between certain gut microbiota and UC, and CD11b on Mo MDSC is a significant mediator between B. bifidum and UC, providing new insights for the clinical treatment of UC.

ObjectiveTo evaluate the causal relationship between lipids and ulcerative colitis (UC) through Mendelian Randomization (MR), and to further investigate the involvement of immune cells in mediating this process.MethodsUtilizing summary statistics from genome-wide association studies (GWAS) of individuals with European ancestry, we analyzed the causal link between 179 lipid types and UC (2,569 UC cases and 453,779 controls) through Two-sample Mendelian randomization (2SMR) and Bayesian-weighted MR (BWMR). Based on this, a mediation screening of 731 immune cell phenotypes was conducted to identify exposure and mediator factors. Lastly, the role and proportion of immune cells in mediating the causal effects of lipids on UC were assessed via reverse MR (RMR) and two-step MR.ResultsThe results of MR showed that there was a causal relationship between the six genetically predicted lipid types and UC (P

The human intestinal tract constitutes a complex ecosystem, made up of countless gut microbiota, metabolites, and immune cells, with hypoxia being a fundamental environmental characteristic of this ecology. Under normal physiological conditions, a delicate balance exists among these complex “residents”, with disruptions potentially leading to inflammatory bowel disease (IBD). The core pathology of IBD features a disrupted intestinal epithelial barrier, alongside evident immune and microecological disturbances. Central to these interconnected networks is hypoxia-inducible factor-1α (HIF-1α), which is a key regulator in gut cells for adapting to hypoxic conditions and maintaining gut homeostasis. Short-chain fatty acids (SCFAs), as pivotal gut metabolites, serve as vital mediators between the host and microbiota, and significantly influence intestinal ecosystem. Recent years have seen a surge in research on the roles and therapeutic potential of HIF-1α and SCFAs in IBD independently, yet reviews on HIF-1α-mediated SCFAs regulation of IBD under hypoxic conditions are scarce. This article summarizes evidence of the interplay and regulatory relationship between SCFAs and HIF-1α in IBD, pivotal for elucidating the disease’s pathogenesis and offering promising therapeutic strategies.

Purpose/aim of the study: To investigate high-risk human papillomavirus (HPV) infection clearance following thin loop electrosurgical excision procedure (t-LEEP) among patients with cervical benign lesion. Materials and Methods: This retrospective study analyzed clinical data from patients with cervical benign lesion and HPV infection, who had undergone t-LEEP (T-Group), compared with patients with HPV infection undergone no treatment (NT-Group). Both groups attended regular follow-up between January 2008 and January 2012. Kaplan–Meier analysis was used to compare the HPV clearance time. Results: The average clearance time was 7.7 months (M) (95% confidence interval [CI]: 6.5–8.9 M) in T-Group, and 10.4 M (95%CI: 9.4–11.3 M) in NT-Group, with significant difference between groups (p = 0.003). Among patients with low viral load, the HPV clearance times were 7.6 M (95%CI: 6.3–9.0 M) in T-Group and 9.7 M (95%CI: 8.6–10.8 M) in NT-Group (p = 0.042). Among patients with high viral load, the HPV clearance times were 8.0 M (95%CI: 5.3–10.6 M) in T-Group and 11.4 M (95%CI: 9.7–13.1 M) in NT-Group (p = 0.041). The average time of HPV clearance in T-Group was shorter than NT-Group in all age groups, with significant differences in ≤29Y-group (p = 0.008) and 30–39Y-group (p = 0.005). The accumulated clearance rate of HPV infection at sixth month and 12th month were 24.5% and 67.9% in T-Group, 7.8% and 43.1% in NT-Group, with significant differences (p = 0.001 at 6th month, p = 0.032 at 12th month). Conclusions: T-LEEP accelerates the clearance of high-risk HPV infection and make the HPV infection rates dropped rapidly in the first year.