Phenethylamine-producing gut bacteria induces diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis

Zhai, L.; Huang, C.; Ning, Z.; Zhang, Y.; Zhuang, M.; Yang, W.; Wang, X.; Wang, J.; Zhang, E. L.; Xiao, H.; Zhao, L.; Lam, Y. Y.; Chow, C. F. W.; Huang, J.; Yuan, S.; Chan, K. M.; Wong, H. L. X.; Bian, Z.-x.

doi:10.1101/2022.03.05.483096

bioRxiv · 10.1101/2022.03.05.483096

Phenethylamine-producing gut bacteria induces diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis

Zhai, L.·Huang, C.·Ning, Z.·Zhang, Y.·Zhuang, M.·Yang, W.·Wang, X.·Wang, J.·Zhang, E. L.·Xiao, H.·Zhao, L.·Lam, Y. Y.·Chow, C. F. W.·Huang, J.·Yuan, S.·Chan, K. M.·Wong, H. L. X.·Bian, Z.-x.

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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

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Zhai, L., Huang, C., Ning, Z., Zhang, Y., Zhuang, M., Yang, W., Wang, X., Wang, J., Zhang, E. L., Xiao, H., Zhao, L., Lam, Y. Y., Chow, C. F. W., Huang, J., Yuan, S., Chan, K. M., Wong, H. L. X., Bian, Z.-x.. 2022-03-05. Phenethylamine-producing gut bacteria induces diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis. https://doi.org/10.1101/2022.03.05.483096

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