Figure 1.

Host and gut microbiota metabolic interactions. A, The active metabolite of irinotecan, SN-38, is glucuronidated to inactive SN-38-G by host Phase II UDP-glucuronosyltransferase enzymes (UGTs) in the liver. In the gut, SN-38-G encounters microbial β-glucuronidase (GUS) enzymes that remove the glucuronic acid sugar, reactivating SN-38 in the GI lumen and causing local GI toxicity. B, Estrone is sulfated in the liver via the action of sulfotransferases (SULTs) sent to the gut for excretion. The gut lumen contains microbial sulfatases capable of removing the inactivating sulfate moiety, reactivating hormones for reabsorption and systemic recirculation, contributing to systemic diseases, including hormone driven cancers. C, After Phase I metabolism, hydroxylated estrogens may serve as substrates for gut microbial COMTs, which, methylate catechol-estrogens, contributing to total estrogenic burden and thus may also contribute to systemic diseases, including hormone driven cancers. D, 2-Naphthalene is acetylated by human N-acetyltransferases (NATs); these acetylated compounds may encounter gut microbial small molecule deacetylases that reactivate the mutagen and facilitate gut epithelial tumorigenesis, exerting systemic effects and potentially contributing to carcinogenesis.