<div>Abbreviations: 4-HPA, 4-hydroxyphenylacetic acid; 5-FU, 5-fluorouracil;
APAP, acetaminophen; AVPR1A/B, arginine vasopressin receptor 1A/B; BBB,
blood brain barrier; DOPA, 3,4-dihydroxyphenylacetic acid; FMT, fecal
microbiota transplantation; FOXP<sup>+</sup>, forkhead box
P3-positive; GABA, γ-aminobutyric acid; GSH, glutathione; MMF,
mycophenolate mofetil; MTX, methotrexate; OXTR, oxytocin receptor; PPD,
1-phenyl-1,2-propanedione; TLRs, toll-like receptors.</div><div>↑ signifies that toxicity of drugs is enhanced after intervention and ↓
signifies that toxicity of drugs is decreased after intervention.</div><div>In conclusion, gut microbiota modulates drug toxicity within the
following aspects (Table 1): (a) gut-derived endogenous metabolites
inhibit drug metabolism by competitive effects and lead to drug
accumulation; (b) gut-derived endogenous and exogenous metabolites
restore gut dysbiosis caused by drugs and ameliorate drug toxicity; (c)
specific gut microbial enzymes transform drugs into toxic or nontoxic
metabolites; (d) prebiotics, probiotics, and diet intervention attenuate
drug toxicity by regulating gut microbiota; (e) gut microbial
metabolites inactivate metabolic enzymes of drugs and also lead to drug
accumulation; (f) gut microbiota translocation induced by drugs causes
damages especially in the brain. Currently, high-throughput technologies
such as sequencing analysis and omics technologies facilitate the
unprecedented development of mechanistic studies of gut microbiota. In
terms of drug toxicity, special attention should be given to drug
metabolisms both in the liver and gut, which appeals for development in
analytical methods. The utilization of gut microbiota as biomarkers of
diseases and guidance for personalized medicine is a trend of the
future.</div><div><b>Declarations of interest</b> : None.</div><div><b>Acknowledgements</b> : This work was supported by National Natural
Science Foundation of China (grant number:
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