Highlights d A B. thetaiotaomicron operon is required for activation of plant glucosinolates d Operon expression in inactive B. fragilis results in glucosinolate metabolism d Glucosinolate metabolism encoded by BT2159-BT2156 requires multiple enzymes d Monoassociation of mice with BtD2157 reduces host exposure to isothiocyanates
Diet is the largest source of plant-derived metabolites that influence human health. The gut microbiota can metabolize these molecules, altering their biological function. However, little is known about the gut bacterial pathways that process plant-derived molecules. Glucosinolates are well-known metabolites in brassica vegetables and metabolic precursors to cancer-preventive isothiocyanates. Here, we identify a genetic and biochemical basis for isothiocyanate formation 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.with the induction of Nrf2, ITC have also been shown to interact with sensory and inflammatory pathways. Allyl ITC, derived from the GS sinigrin, is an agonist of the transient receptor potential ion channel TRPA1, which is involved in signaling inflammatory pain (Bellono et al., 2017), while sulforaphane has been shown to covalently modify lipopolysaccharide-activated Toll-like receptor 4 (TLR4), resulting in the reduced secretion of pro-inflammatory cytokines in human peripheral blood mononuclear cells and monocytes (Folkard et al., 2014).Plant and gut bacterial metabolism have been identified as two different routes for the conversion of GS into ITC products required for biological activity. Like many phytonutrients relevant to human health, GS in crucifers are involved in chemical defense in planta (Halkier and Gershenzon, 2006). These metabolites are stored in the plant tissue in an inert, pro-drug-like state and are converted into an active state by myrosinase enzymes, thio-specific glucoside hydrolases found in cruciferous vegetables (Figure 1A). GS are sequestered in vacuoles under normal conditions, while myrosinases are expressed in distinct, specialized myrosin cells (Kissen et al., 2009). Upon disruption of the plant tissue, myrosinases mediate the hydrolysis of GS into a variety of possible products, including ITC, nitriles, and epithionitriles, determined by environmental pH and the presence of specifier proteins.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.