Gut microbiota influences gastric cancer through the mediation of inflammatory proteins: A Mendelian randomization analysis

A robust correlation exists between gastric cancer (GC) and intestinal flora, potentially facilitated by inflammatory proteins. Nevertheless, the precise relationship between GC, intestinal flora, and their respective mediators remains unclear. The objective of this study is to employ a Mendelian randomization (MR) study to determine the cause-and-effect link between GC, inflammatory proteins, and gut microbiota. The genome-wide association study data pertaining to intestinal microbiota, GC, and 91 inflammatory proteins were obtained from a public database and subjected to MR analysis to ascertain the causal relationship between intestinal microbiota and GC. To evaluate the possible mediating function of latent inflammatory proteins in this process, a two-step MR study was used. Inverse-variance weighting was the primary analytical technique used; sensitivity, heterogeneity, and horizontal multiplicity studies were also carried out. Our MR analysis revealed potential associations between 11 bacterial genera in the gut microbiota and GC in Europeans, with 3 genera suggesting an increased risk and 8 a protective role. Among the inflammatory proteins, 3 demonstrated potential associations with GC, with 1 indicating a higher risk and 2 a protective effect. A two-step MR analysis indicated that genus Ruminococcaceae UCG014 may mediate an increased risk of GC through the downregulation of C-X-C motif chemokine 1, with a mediation ratio of 7.79%. The current research offers evidence that intestinal flora influences the risk of GC development through inflammatory proteins by means of MR analysis. The results of the MR analysis indicated that in European populations, certain microbial taxa may influence GC risk through C-X-C motif chemokine 1.