Microbial liberation of N-methylserotonin from orange fiber in gnotobiotic mice and humans

WashU Affiliated Authors: Nathan D. Han, Jiye Cheng, Omar Delannoy-Bruno, Daniel Webber, Chandani Desai, StaceyMarion, Michael J.Barratt, Andrew C.Heat, Jeffrey I.Gordon

Departments: Dept. of Pathology and Immunology, The Edison Family Center for Genome Sciences and Systems Biology, Center for Gut Microbiome and Nutrition Research, Dept. of Psychiatry,

Abstract: Plant fibers in byproduct streams produced by non-harsh food processing methods represent biorepositories of diverse, naturally occurring, and physiologically active biomolecules. To demonstrate one approach for their characterization, mass spectrometry of intestinal contents from gnotobiotic mice, plus in vitro studies, revealed liberation of N-methylserotonin from orange fibers by human gut microbiota members including Bacteroides ovatus. Functional genomic analyses of B. ovatus strains grown under permissive and non-permissive N-methylserotonin “mining” conditions revealed polysaccharide utilization loci that target pectins whose expression correlate with strain-specific liberation of this compound. N-methylserotonin, orally administered to germ-free mice, reduced adiposity, altered liver glycogenesis, shortened gut transit time, and changed expression of genes that regulate circadian rhythm in the liver and colon. In human studies, dose-dependent, orange-fiber-specific fecal accumulation of N-methylserotonin positively correlated with levels of microbiome genes encoding enzymes that digest pectic glycans. Identifying this type of microbial mining activity has potential therapeutic implications.

Citation or DOI: Nathan D. Han, Jiye Cheng, Omar Delannoy-Bruno, Daniel Webber, Nicolas Terrapon, Bernard Henrissat, Dmitry A. Rodionov, Aleksandr A. Arzamasov, Andrei L. Osterman, David K. Hayashi, Alexandra Meynier, Sophie Vinoy, Chandani Desai, Stacey Marion, Michael J. Barratt, Andrew C. Heath, Jeffrey I. Gordon, Microbial liberation of N-methylserotonin from orange fiber in gnotobiotic mice and humans, Cell, Volume 185, Issue 16, 4 August 2022, Pages 3056-3057