Presented by: Gavin Kuziel
The interaction between diet and the gut microbiome is instrumental in affecting host health and disease. For example, complex dietary carbohydrates actively shape the microbiome as a principal carbon source and concomitantly affect host physiology via microbiome products of carbohydrate fermentation that drive host homeostasis. In contrast, little is known about the interaction between the microbiome and “dietary dark matter”, the additional millions of chemically-diverse plant secondary metabolites, phytochemicals, that we consume daily.
Here, we asked whether chemically-diverse plant secondary metabolites are transformed by gut bacteria, and if products of phytochemical catabolism affect microbiome composition or host physiology. Across a collection of taxonomically-diverse gut bacteria, we identified broad phytochemical glycoside catabolism across diverse species. Glycosides are small molecules (aglycones) conjugated to simple carbohydrates. The Bacteroidales exhibited an enhanced capacity for phytochemical catabolism. Genetic dissection of this catabolism in two prevalent and abundant Bacteroides species, Bacteroides ovatus (Bo) and Bacteroides uniformis (Bu), identified two novel divergent systems for phytochemical catabolism. Whereas Bo harbored a non-specific, generalist system for glycoside and disaccharide catabolism, Bu harbored a multiple-locus glycoside catabolism system in which some loci were selective for glycosides and not chemically-similar disaccharides. Furthermore, we demonstrated that microbial catabolism of glycosides liberates their aglycones, expanding the chemical diversity of these factors and activating new bioactivities unique from their parent glycosides. In a model of colitis, mice were protected from disease when treated with Bu (but not a mutant Bu unable to catabolize glycosides) and the ancient medicinal glycoside salicin. This suggests saligenin, salicin’s aglycone, is the active anti-inflammatory agent. This protection was unique to salicin bioactivation, as mice treated with Bu and arbutin, a salicin analog, were not protected from disease. Our findings highlight new mechanistic insights into microbiome-dependent transformation of dietary phytochemicals and the effects of these metabolic transformations on host homeostasis.
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