4.8 Article

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

Journal

CELL
Volume 185, Issue 14, Pages 2495-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.202.06.004

Keywords

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Funding

  1. NIH [DK70977]
  2. Washington University School of Medicine-Centene Program in Personalized Medicine, and Mondelez Global LLC

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Plant fibers in byproduct streams produced by non-harsh food processing methods contain diverse and naturally occurring biomolecules with physiological activities. It has been found that human gut microbiota can release N-methylserotonin from orange fibers, and certain strains of Bacteroides ovatus have the ability to specifically liberate this compound. Orally administered N-methylserotonin has various effects on mice and its fecal accumulation in humans is positively correlated with microbial genes encoding enzymes that digest pectic glycans.
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.

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