Exploring the Gut Ecosystem: Mechanism Studies From the Gut Microbiota to Inflammatory Cytokines to Inflammatory...

A potential association exists among gut microbiota, inflammatory mediators and inflammatory bowel disease (IBD), yet the precise biological mechanisms underlying these interconnections remain to be fully elucidated. Single nucleotide polymorphisms (SNPs) associated with gut microbiota were collected from the MiBioGen consortium. SNPs associated with IBD were sourced from GWAS research. Furthermore, a two-step MR approach was employed to clarify the potential mediating role of inflammatory factors in the causal relationship between gut microbiota and IBD. The genus Eubacterium ruminantium group (odds ratio [OR] = 1.087, 95% confidence interval [CI], 1.006-1.174, p = 0.035), genus Lachnospiraceae FCS020 group (OR, 1.172, 95% CI, 1.035-1.326, p = 0.012) were identified as a risk factor for IBD. Conversely, the family Bifidobacteriaceae performed a suggestively positive impact on the protective role against IBD (OR, 0.834, 95% CI, 0.728-0.956; p = 0.009), as well as family Clostridiaceae1 (OR, 0.827, 95% CI, 0.710-0.965; p = 0.016), family Lactobacillaceae (OR, 0.889, 95% CI, 0.798-0.991; p = 0.033) were found to be protective factors. Furthermore, our study indicated that the genus Lachnospiraceae FCS020 group contributed to the risk of IBD by affecting Interleukin-18 (IL-18), a mediation effect (OR = 1.015, 95% CI, 1.000-1.037, mediation proportion = 9.494%). This study offers genetic evidence from the perspective of bioinformatics to support potential causal mechanisms linking gut microbiota and IBD. Furthermore, from the perspective of gene prediction, it revealed the mediating role of IL-18 in the pathogenicity of the gut microbiota on IBD.