Methods: We applied metagenomics and metabolomics analysis to study the changes in gut microbiota and gut microbial metabolites. We conducted in vitro, ex vivo, and in vivo studies to examine the effects and underlying mechanisms of gut bacteria and their metabolites on 5-HT production and gastrointestinal transit.
Results: Herein, we identified a human gut bacterium Ruminococcus gnavus as a major factor that underlies the motility disorder in IBS-D. We showed that R. gnavus is highly enriched in IBS-D patients and positively correlated with the severity of diarrheal symptoms (IDDF2022-ABS-0035 Figure 1. The enrichment of Ruminococcus gnavus in IBS-D patients and its positive correlation with serum 5-HT level and diarrhea symptoms). Monocolonization of R. gnavus induces IBS-D-like symptoms including increased gastrointestinal transit and colonic secretion in pseudo-germ-free mice by stimulating the production of peripheral 5-HT (IDDF2022-ABS-0035 Figure 2. Monoassociation of Ruminococcus gnavus induces IBS-D-like symptoms and elevation of PEA level in pseudo-germ-free mice). Metabolically, we discovered that phenethylamine (PEA) derived from R. gnavus-mediated metabolism of dietary aromatic amino acids directly stimulates the 5-HT biosynthesis in intestinal enterochromaffin cells and this is mediated by its activation of a G-protein coupled receptor (TAAR1), thereby contributing to elevated GI transit and colonic secretion in IBS-D (IDDF2022-ABS-0035 Figure 3. PEA activates 5-HT production accelerate GI transit and increase colonic secretion in vitro and in vivo) (IDDF2022-ABS-0035 Figure 4. PEA stimulates 5-HT production via a TAAR1-dependent mechanism). More importantly, pharmacological inhibition of TAAR1 activation alleviates IBS-D-like symptoms in mice transplanted with fecal microbiota from IBS-D patients, a preclinical model of IBS-D (IDDF2022-ABS-0035 Figure 5. In vivo pea production by IBS-D associated bacteria enhance 5-HT synthesis and induce diarrhea like symptoms).
|Number of pages
|Early online date
|2 Sept 2022
|Published - Sept 2022
|International Digestive Disease Forum 2022, IDDF 2022 - Hong Kong, Hong Kong
Duration: 2 Sept 2022 → 4 Sept 2022
https://gut.bmj.com/content/71/Suppl_2 (Conference proceedings)