Connecting the dots: targeting gut microbiota in drug toxicity

Abstract

Gut microbiota has been demonstrated to have a vast influence on human health in recent decades and its role in initiating, aggravating, or ameliorating diseases is emerging. Therapeutic strategies have therefore increasingly developed by targeting gut microbial modulation. Recently, its contribution to heterogeneous toxicological responses is also gaining attention, especially in drug-induced toxicity. Oral drugs interact directly with gut microbiota within the gastrointestinal tract and a number of them elicit toxicity mediated by intestinal microbiota. Present studies focus more on the unidirectional influence of how xenobiotics disturb intestinal microbial composition and function and consequently induce altered homeostasis. However, interactions between gut microbiota and xenobiotics are bidirectional and the impact of gut microbiota on xenobiotics especially on drugs should not be neglected. Thus, in this review, we intend to focus on how gut microbiota modulates drug toxicity by highlighting gut microbiota, microbial enzyme, and metabolites to proffer references for seeking common countermeasures in coping with drug toxicity by targeting gut microbiota. Moreover, we give a hypothesis that drugs capable of inducing gut dysbiosis tend to more or less impact the gut-connected organs as evidenced by the drug-induced hepatic encephalopathy, indicating an underlying link among the gut, liver, brain, and other possible organs in drug-induced toxicity.