Effects of Trimethylamine N-Oxide on Inflammation and the Gut Microbiota Alteration Induced By Helicobacter Pylori

Diet is one of the factors contributing to symptom of Helicobacter pylori (H. pylori) infection. Trimethylamine N-oxide (TMAO), a diet-related microbial metabolite, is associated with inflammatory and metabolic diseases. The aim of this study is to investigate the effects of TMAO on inflammation and gut microbiota composition in H. pylori-infected mice via biochemical analyses, gene expression profiling and 16S rRNA sequencing. The in vitro experiments showed that TMAO not only increased the expression of growth- and metabolism-associated genes and the urease activity of H. pylori, but also elevated the production of virulence factors. Moreover, TMAO altered the immune response and promoted expression of IL-6, CXCL1 of GES-1 cells with H. pylori infection. Further in vivo experiments showed that TMAO intake increased the production of inflammatory markers and reduced the richness and diversity of the gut microbiota in H. pylori-infected mice. Further analysis showed that TMAO enhanced the relative abundance of Escherichia_Shigella in H. pylori-infected mice, which had positive correlations with the levels of LPS, IL-6, and CXCL1. Collectively, our results suggest that TMAO may promote H. pylori-induced inflammation by increasing the viability and virulence of H. pylori and may aggravate inflammation in association with the gut microbiota in H. pylori-infected mice. This study may provide a novel insight into the mechanism for the effect of diet-derived metabolites such as TMAO on H. pylori-induced disease development.