Abstract

Despite the strong association between gut microbial dysbiosis, serotonin (5-HT) dysregulation and diarrhea-predominant irritable bowel syndrome (IBS-D), the mechanism by which changes in the gut microbiota contribute to the pathogenesis of IBS-D, particularly the role of dysregulated 5-HT production, remains unclear. The present study identified Ruminococcus gnavus in the human gut microbiota as a key risk factor of IBS-D. R. gnavus was significantly enriched in IBS-D patients and exhibited positive correlation with serum 5- HT level and severity of diarrhea symptoms. We showed that R. gnavus induced diarrhea-like symptoms in mice by promoting microbial shunting of essential aromatic amino acids to aromatic trace amines including phenethylamine and tryptamine, thereby stimulating the biosynthesis of peripheral 5-HT, a potent stimulator for gastrointestinal transit. This study identify gut-microbial metabolism of dietary amino acids as a cause of IBS-D and lays a foundation for developing novel therapeutic target for the treatment of IBS-D. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/483096v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@48400aorg.highwire.dtl.DTLVardef@1645aedorg.highwire.dtl.DTLVardef@18d878dorg.highwire.dtl.DTLVardef@be4b30_HPS_FORMAT_FIGEXP M_FIG C_FIG