A Metabolic Pathway for Activation of Dietary Glucosinolates by a Human Gut Symbiont.

TitleA Metabolic Pathway for Activation of Dietary Glucosinolates by a Human Gut Symbiont.
Publication TypeJournal Article
Year of Publication2020
AuthorsLiou, CS, Sirk, SJ, Diaz, CAC, Klein, AP, Fischer, CR, Higginbottom, SK, Erez, A, Donia, MS, Sonnenburg, JL, Sattely, ES
JournalCell
Volume180
Issue4
Pagination717-728.e19
Date Published2020 02 20
ISSN1097-4172
KeywordsAnimals, Bacteroides thetaiotaomicron, Dietary Carbohydrates, Gene Expression Regulation, Bacterial, Glucosinolates, Humans, Intestines, Male, Mice, Operon, Symbiosis
Abstract

<p>Consumption of glucosinolates, pro-drug-like metabolites abundant in Brassica vegetables, has been associated with decreased risk of certain cancers. Gut microbiota have the ability to metabolize glucosinolates, generating chemopreventive isothiocyanates. Here, we identify a genetic and biochemical basis for activation of glucosinolates to isothiocyanates by Bacteroides thetaiotaomicron, a prominent gut commensal species. Using a genome-wide transposon insertion screen, we identified an operon required for glucosinolate metabolism in B. thetaiotaomicron. Expression of BT2159-BT2156 in a non-metabolizing relative, Bacteroides fragilis, resulted in gain of glucosinolate metabolism. We show that isothiocyanate formation requires the action of BT2158 and either BT2156 or BT2157 in vitro. Monocolonization of mice with mutant BtΔ2157 showed reduced isothiocyanate production in the gastrointestinal tract. These data provide insight into the mechanisms by which a common gut bacterium processes an important dietary nutrient.</p>

DOI10.1016/j.cell.2020.01.023
Alternate JournalCell
PubMed ID32084341
Grant ListR01 DK085025 / DK / NIDDK NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States