Connecting the dots: targeting gut microbiota in drug toxicity
AbstractGut 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.