Abstract：
Diarrhea-predominant irritable bowel syndrome (IBS-D), a globally prevalent functional gastrointestinal (GI) disorder, is associated with elevated serotonin that increases gut motility. While anecdotal evidence suggests that the gut microbiota contributes to serotonin biosynthesis, mechanistic insights are limited. We determined that the bacterium Ruminococcus gnavus plays a pathogenic role in IBS-D. Monocolonization of germ-free mice with R. gnavus induced IBS-D-like symptoms, including increased GI transit and colonic secretion, by stimulating the production of peripheral serotonin. R. gnavus-mediated catabolism of dietary phenylalanine and tryptophan generated phenethylamine and tryptamine that directly stimulated serotonin biosynthesis in intestinal enterochromaffin cells via a mechanism involving activation of trace amine-associated receptor 1 (TAAR1). This R. gnavus-driven increase in serotonin levels elevated GI transit and colonic secretion but was abrogated upon TAAR1 inhibition. Collectively, our study provides molecular and pathogenetic insights into how gut microbial metabolites derived from dietary essential amino acids affect serotonin-dependent control of gut motility.
摘要：
腹泻型肠易激综合征(IBS-D),一种全球流行的功能性胃肠(GI)疾病，与增加肠道运动的血清素升高有关。虽然轶事证据表明肠道微生物群有助于5-羟色胺的生物合成，机械见解是有限的。我们确定了细菌Ruminococcusgnavus在IBS-D中起致病作用。用R.gnavus诱导的IBS-D样症状的无菌小鼠的单种化，包括胃肠道转运和结肠分泌增加，通过刺激外周血清素的产生。gnavus介导的饮食苯丙氨酸和色氨酸的分解代谢产生的苯乙胺和色胺通过涉及痕量胺相关受体1（TAAR1）激活的机制直接刺激肠道肠嗜铬细胞中5-羟色胺的生物合成。这种由R.gnavus驱动的5-羟色胺水平的增加升高了GI转运和结肠分泌，但在TAAR1抑制后被废除。总的来说，我们的研究提供了来自膳食必需氨基酸的肠道微生物代谢产物如何影响5-羟色胺依赖的肠道运动控制的分子和致病机制。
