A metabolic pathway for glucosinolate activation by the human gut symbiont Bacteroides thetaiotaomicron

ABSTRACT 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.