Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology · 2025
A Systematic analysis of gut microbiota in anorectal abscess and anal Fistula, with the mediating role of immune cells.
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Shen Pan, Luo Qinghua, Ding Yifan, Xiong Hao, Zhang Leichang
Аннотация
BACKGROUND AND STUDY AIMS: This study aimed to investigate the causal relationships between gut microbiota, immune cells, and the development of anorectal abscess and anal fistula through Mendelian randomization (MR) analysis. The objective was to identify gut microbial taxa and immune cell phenotypes that contribute to disease pathogenesis, thereby providing new insights into the underlying mechanisms.
MATERIALS AND METHODS: Two-sample MR analysis was conducted using genetic data from large-scale genome-wide association studies (GWAS), encompassing 211 gut microbiota taxa and 731 immune cell phenotypes. The inverse variance weighted (IVW) method served as the primary analysis, complemented by sensitivity analyses such as MR-Egger, MR-PRESSO, and leave-one-out tests. Mediation MR analysis was employed to assess the role of immune cells as mediators.
RESULTS: Ten gut microbiota taxa were significantly associated with anorectal abscess, while six taxa were linked to anal fistula. Protective taxa included Butyrivibrio, Ruminiclostridium 5, and Sutterella, while Porphyromonadaceae, Actinomyces, and Faecalibacterium were identified as risk factors. Mediation analysis revealed 16 immune cell phenotypes involved in the gut microbiota-disease pathway. Specifically, CD45 on CD33- HLA DR- mediated 17.28 % of the effect of Actinomyces on anorectal abscess, while CD4 on HLA DR + CD4 + mediated -18.26 % of the protective effect of Butyrivibrio on anorectal abscess.
CONCLUSION: To the best of our knowledge, this study represents the first comprehensive evaluation of causal relationships among gut microbiota, immune cell phenotypes, and anorectal diseases. The findings underscore specific gut microbiota and immune cell phenotypes as critical mediators in disease pathogenesis, offering promising targets for therapeutic intervention and precision treatment strategies.
MATERIALS AND METHODS: Two-sample MR analysis was conducted using genetic data from large-scale genome-wide association studies (GWAS), encompassing 211 gut microbiota taxa and 731 immune cell phenotypes. The inverse variance weighted (IVW) method served as the primary analysis, complemented by sensitivity analyses such as MR-Egger, MR-PRESSO, and leave-one-out tests. Mediation MR analysis was employed to assess the role of immune cells as mediators.
RESULTS: Ten gut microbiota taxa were significantly associated with anorectal abscess, while six taxa were linked to anal fistula. Protective taxa included Butyrivibrio, Ruminiclostridium 5, and Sutterella, while Porphyromonadaceae, Actinomyces, and Faecalibacterium were identified as risk factors. Mediation analysis revealed 16 immune cell phenotypes involved in the gut microbiota-disease pathway. Specifically, CD45 on CD33- HLA DR- mediated 17.28 % of the effect of Actinomyces on anorectal abscess, while CD4 on HLA DR + CD4 + mediated -18.26 % of the protective effect of Butyrivibrio on anorectal abscess.
CONCLUSION: To the best of our knowledge, this study represents the first comprehensive evaluation of causal relationships among gut microbiota, immune cell phenotypes, and anorectal diseases. The findings underscore specific gut microbiota and immune cell phenotypes as critical mediators in disease pathogenesis, offering promising targets for therapeutic intervention and precision treatment strategies.