Inter-individual responses to medicinal drugs vary widely in clinic,which drives the urgent need of precision medicine for minimizing adverse reactions and maximalizing therapeutic effects among patients[1].In additio...Inter-individual responses to medicinal drugs vary widely in clinic,which drives the urgent need of precision medicine for minimizing adverse reactions and maximalizing therapeutic effects among patients[1].In addition to genetic factors,increasing evidence suggests that gut microbiome plays a crucial role in affecting either pharmacodynamics or pharmacokinetics[2].In recent years,at least two ways have been demonstrated through which gut microbiome jointly affects drug metabolism or efficacy with host.One is the microbial metabolism on drugs.Zimmermann et al.[3]systematically studied the direct interaction between microorganisms and drugs.They found that 2/3 of the 271 selected orally administered drugs could be metabolized by at least one strain.They also verified that 30 enzymes encoded by microorganisms have the ability to transform 20 drugs into 59 candidate metabolites.The direct interaction between gut microbiota and drugs,including chemical modification(such as sulfasalazine[4]),inactivation(such as digoxin[5])or changes in toxicity(such as irinotecan[6]).Another way is the bioaccumulation of drugs in gut bacteria that alters drug availability and metabolism.Klünemann et al.[7]investigated the depletion of 15 drugs with different structures by 25 representative strains.This study reveals 70 interactions between bacteria and drugs,of which 29 have not been reported in previous studies,and more than half of the new interactions can be attributed to bioaccumulation.展开更多
基金supported by the Program of Shanghai Academic/Technology Research Leader(No.21XD1403500).
文摘Inter-individual responses to medicinal drugs vary widely in clinic,which drives the urgent need of precision medicine for minimizing adverse reactions and maximalizing therapeutic effects among patients[1].In addition to genetic factors,increasing evidence suggests that gut microbiome plays a crucial role in affecting either pharmacodynamics or pharmacokinetics[2].In recent years,at least two ways have been demonstrated through which gut microbiome jointly affects drug metabolism or efficacy with host.One is the microbial metabolism on drugs.Zimmermann et al.[3]systematically studied the direct interaction between microorganisms and drugs.They found that 2/3 of the 271 selected orally administered drugs could be metabolized by at least one strain.They also verified that 30 enzymes encoded by microorganisms have the ability to transform 20 drugs into 59 candidate metabolites.The direct interaction between gut microbiota and drugs,including chemical modification(such as sulfasalazine[4]),inactivation(such as digoxin[5])or changes in toxicity(such as irinotecan[6]).Another way is the bioaccumulation of drugs in gut bacteria that alters drug availability and metabolism.Klünemann et al.[7]investigated the depletion of 15 drugs with different structures by 25 representative strains.This study reveals 70 interactions between bacteria and drugs,of which 29 have not been reported in previous studies,and more than half of the new interactions can be attributed to bioaccumulation.
