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+, 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.
↑ signifies that toxicity of drugs is enhanced after intervention and ↓ signifies that toxicity of drugs is decreased after intervention.
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.
Declarations of interest : None.
Acknowledgements : This work was supported by National Natural Science Foundation of China (grant number: 81973457).
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