Microbial Cysteine Degradation Drives Cryptic Sulfide Redox Chemistry in the Gut

Abstract Although microbial biochemistry shapes a dynamic environment in the gut, how bacterial metabolites such as hydrogen sulfide (H2S) mechanistically alter the gut chemical landscape is poorly understood. Here we show for the first time that H2S generated during cysteine metabolism drives the reduction of azo (R-N=N-R’) xenobiotics in bacterial cultures, human fecal microbial communities, and in vivo mouse models. Thus, chemical-chemical interactions, derived from microbial community metabolism, are a key missing feature shaping xenobiotic metabolism in the gut. Changing dietary levels of the H2S xenobiotic redox partner Red 40 transiently decreases mouse fecal sulfide, confirming that a xenobiotic can attenuate sulfide concentration in vivo. Cryptic H2S redox thus modulates sulfur homeostasis in the gut and the fate of xenobiotics to which humans are regularly exposed.