Bacterial hydrogen sulfide drives cryptic redox chemistry in gut microbial communities

Microbial biochemistry contributes to a dynamic environment in the gut. Yet, how bacterial metabolites such as hydrogen sulfide (H₂S) mechanistically alter the gut chemical landscape is poorly understood. Here we show that microbially generated H₂S drives the abiotic reduction of azo (R-N = N-R') xenobiotics, which are commonly found in Western food dyes and drugs. This nonenzymatic reduction of azo compounds is demonstrated in Escherichia coli cultures, in human faecal microbial communities and in vivo in male mice. Changing dietary levels of the H₂S xenobiotic redox partner Red 40 transiently decreases mouse faecal sulfide levels, demonstrating that a xenobiotic can attenuate sulfide concentration and alleviate H₂S accumulation in vivo. Cryptic H₂S redox chemistry thus can modulate sulfur homeostasis, alter the chemical landscape in the gut and contribute to azo food dye and drug metabolism. Interactions between chemicals derived from microbial communities may be a key feature shaping metabolism in the gut.