Figure 1. Gut microbial modulation of xenobiotic metabolism.

Direct mechanisms include (i) production of active compounds, (ii) detoxification, and (iii) direct binding to bacterial cells. Indirect mechanisms involve microbial manipulation of host physiology. (iv) Microbial participation in enterohepatic cycling: (1) compounds are inactivated by conjugation in the liver; (2) the conjugated compound passes into bile and is excreted into the intestinal lumen; (3) microbial enzymes release the conjugate group, reactivating the compound; and (4) the active compound reenters circulation. (v) Altered expression of host genes involved in xenobiotic metabolism. (vi) Altered kinetics due to microbial metabolites competing with xenobiotics for enzyme binding sites. (vii) Microbial production of metabolic pathway intermediates. (viii) Stimulation of immune responses through translocation or inflammation.