Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China; Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China.
Core Laboratory, School of Medicine, Sichuan Provincial People's Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu 610072, PR China.
Int Immunopharmacol. 2020 Apr;81:106026. doi: 10.1016/j.intimp.2019.106026. Epub 2019 Nov 20.
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 intake on inflammation and gut microbiota composition in H. pylori-infected mice via 16S rRNA sequencing and biochemical analyses. 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 increased the production of virulence factors. Moreover, 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 increased the relative abundance of Escherichia_Shigella in H. pylori-infected mice, which had positive correlation with the levels of LPS, CRP, and CXCL1. Collectively, our results suggest that TMAO may aggravate 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.
饮食是导致幽门螺杆菌（H. pylori）感染症状的因素之一。三甲胺 N-氧化物（TMAO）是一种与饮食相关的微生物代谢产物，与炎症和代谢性疾病有关。本研究旨在通过 16S rRNA 测序和生化分析，研究 TMAO 摄入对 H. pylori 感染小鼠炎症和肠道微生物组成的影响。体外实验表明，TMAO 不仅增加了 H. pylori 生长和代谢相关基因的表达和脲酶活性，而且增加了毒力因子的产生。此外，TMAO 摄入增加了 H. pylori 感染小鼠炎症标志物的产生，降低了肠道微生物群落的丰富度和多样性。进一步分析表明，TMAO 增加了 H. pylori 感染小鼠中 Escherichia_Shigella 的相对丰度，与 LPS、CRP 和 CXCL1 的水平呈正相关。总之，我们的研究结果表明，TMAO 可能通过增加 H. pylori 的活力和毒力来加重 H. pylori 诱导的炎症，并可能与 H. pylori 感染小鼠的肠道微生物群落一起加重炎症。本研究可能为饮食衍生代谢物如 TMAO 对 H. pylori 诱导疾病发展的影响机制提供新的见解。
