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Published in final edited form as: Expert Opin Drug Metab Toxicol. 2015 Dec 10;12(1):31–40. doi: 10.1517/17425255.2016.1121234

The influence of gut microbiota on drug metabolism and toxicity

Houkai Li 1,*, Jiaojiao He 1, Wei Jia 1,2,*
PMCID: PMC5683181  NIHMSID: NIHMS916953  PMID: 26569070

Abstract

Introduction

Gut microbiota plays critical roles in drug metabolism. The individual variation of gut microbiota contributes to the interindividual differences towards drug therapy including drug-induced toxicity and efficacy. Accordingly, the investigation and elucidation of gut microbial impacts on drug metabolism and toxicity will not only facilitate the way of personalized medicine, but also improve the rational drug design.

Areas covered

This review provide an overview on the microbiota-host cometabolism on drug metabolism and summarize 30 clinical drugs which are co-metabolized by host and gut microbiota. Moreover, this review is specifically focused on elucidating the gut microbial modulation on some clinical drugs, in which the gut microbial influences on drug metabolism, drug-induced toxicity and efficacy are intensively discussed.

Expert opinion

The gut microbial contribution to drug metabolism and toxicity is increasingly recognized, but remains largely unexplored due to the extremely complex relationship between gut microbiota and host. The mechanistic elucidation of gut microbiota in drug metabolism is critical before any practical progress in drug design or personalized medicine could be made by modulating human gut microbiota, which is predominantly relied on the technical innovations such as metagenomics and metabolomics, as well as the integration of multi-disciplinary knowledge.

1. Introduction

The gut microbiome is the collective genome of the whole microbes inhabiting in mammalian gastrointestinal tract, which contains over 1000 species bacteria and about 10 times the number of the host body cells 1, 2. The gut microbiota has been regarded as an indispensable “metabolic organ” in regard to its critical functions in maintaining human health and involvement of various diseases 3. Meanwhile, the gut microbiota also plays crucial roles in drug metabolism by activating or inactivating the pharmacological property of drugs 4. Although the human gastrointestinal tract is mainly dominated by several types of bacteria phyla such as Firmicutes, Bacteroidetes, and Actinobacteria, the entire composition of human gut microbiota is highly variable 5, which contributes to the individually different responses to identical drug therapy in together with genetic polymorphism. However, in the past decades, extensive investigations have been largely focused on the host genetic background for bridging the association between host genetics and drug responses, whereas the roles of gut microbiota were underestimated owing to the complexity of gut microbiota and the difficulty in culture of gut bacteria in vitro 6.

In recent years, the microbial genomics has progressed from culture-dependent to culture-independent strategies (i.e. metagenomics), which facilitates the identification of roles of gut microbiota in diseases and drug metabolism 7. A new term “pharmacomicrobiomics” was coined to denote the effects of gut microbiota variations on pharmacokinetics and pharmacodynamics 6. To date, extensive efforts have been made to describe the effects of gut microbiota on pharmacokinetics, where gut microbiota could impact drug metabolism through several well-established ways including production of microbial metabolites to interfere with drug metabolism 8, production of microbial enzymes to transform drug molecules 9, 10, and modification of drug metabolizing genes or enzymes in host liver or intestine tissues 7. However, given the extreme complexity between gut microbiota and host, the recognition of the gut microbial impacts on drug metabolism is still on the way and is now being accelerated by the striking innovation of systemic approaches such as metagenomics, metabolomics as well. On the other hand, the gut microbial impacts on pharmacodynamics are attracting more and more attention in recent years, due to the exiting progresses in uncovering the gut microbial modulations on drug efficacy.

In this review, we will first provide an overview of the microbiota-host cometabolism focusing on the main drug-metabolizing enzymes in liver, and the gut microbial impacts on drug metabolism. Second, we will discuss some new progresses in gut microbial-modulated drug metabolism in recent years, and summarize 30 drugs which are co-metabolized by gut microbiota and provide information about the type of microbial transformation, microbial-related products, influence on drug efficacy or toxicity, as well as the related bacteria species if available, which are responsible for the drug metabolism. Third, we will discuss the effects of gut microbial modulation on drug efficacy of recent studies, in which the gut microbiota is recognized as a critical factor for influencing the therapeutic outcome of some clinical drugs. The elucidation of these microbial contributions to the variations in drug responses will pave the way towards personalized therapy.

1. Microbiota-host cometabolism on drug metabolism and toxicity

2.1 Host and microbiota drug-metabolizing enzymes

Human beings are living with indispensible symbiotics over the whole life, which shapes the capability of detoxifing xenobiotics (including drugs, dietary compounds) through microbiota-host cometabolism. The host detoxification systems include phase I and phase II reactions. The phase I metabolism, including oxidation, reduction, hydroxylation, etc, is mainly mediated by cytochrome P450 (CYP) enzymes in liver, gut and other tissues, which is to facilitate the excretion of xenobiotics in urine by increasing the polarity of foreign compounds. The phase II metabolism is the conjugation reaction, including glucuronidation and sulfonation. The foreign compounds are conjugated with endogenous metabolites by host enzyme transfer systems to increase their urinary excretion. The phase IIenzymes include sulfotransferase (SULT), uridine 5′-diphospho-glucuronosyltransferase /UDP-glucuronosyltrasnferase (UGT), N-acetyltransferase (NAT) and gluctathione S-transferase (GST) 11. Over 70% of prescribed top 200 drugs are metabolized in liver, whereas about 25% are eliminated in kidney 11, and about 50% of drugs are metabolized through P450 enzyme system highlighting the significance of the P450 enzyme systems in drug metabolism.

In addition to the host drug metabolism system, the gut microbiota also plays important roles in drug metabolism through secretion of microbial drug-metabolizing enzymes or microbiota-host cometabolism. Although, the impacts of gut microbiota on drug metabolism have been investigated for decades, the gut microbial impacts on only about 40 drugs or natural products have been reported so far 4. According to the well-established evidence of gut microbial influence on pharmacokinetics, the gut microbiota usually modulates the oral drug bioavailability or half-life of drugs via microbiota-host cometabolism by altering the capacity of drug-metabolizing enzymes or expression of genes involved in drug metabolism in host tissues 7. Moreover, the individual composition or function of gut microbiota is apt to be influenced by environmental factors such as diets, and antibiotics, or the healthy status of host because lots of diseases are associated with the gut dysbiosis or the vice versa 12. Consequently, the individually different responses towards drug therapy are indispensably associated with the variations of gut microbiota 13. Most drugs are metabolized by host or microbiota-host cometabolism into active, inactive or toxic metabolites. About 30 therapeutic drugs which are metabolized by microbiota-host cometabolism are systemically summarized in Table 1. The following are several examples of clinical drugs with well-established evidence of microbial-modulation on their metabolism and toxicity.

Table 1.

Drugs that are co-metabolized by gut microbiota

Drugs Clinical application Type of microbial metabolism Microbial-related products Influence on drug efficacy or toxicity Related bacteria (if available) Ref
Digoxin Treatment for heart disease Reduction Dihydrodigoxin and dihydrodigoxigenin Decreased cardiac activity Eggerthella lenta 9, 22
L-Dopa Treatment for parkinson’s disease Dehydroxylation m-tyrosine, m-tyramine, m-hydroxyphenylacetic acid Decreased activity 42
Metronidazole Anti-anaerobic bacteria drug Reduction N-(2-hydroxyethyl)-oxamic acid and acetamide Probably increase its liver toxicity 43
Simvastatin Hypolipidemic drug and prevention of cardivascular disease Hydrolysis, demethylation, hydroxylation/dehydroxylation and β-oxidation Lactic acid, 3-hydroxybutanoic acid, cyclohexanecarboxylic acid, 2-hydroxyvaleric acid Altering its lipids-lowering activity 44
Lovastatin Hydrolysis Demethylbutyryl metabolite, hydroxylated metabolite, hydroxy acid metabolite 38
Acetaminophen Anti-analgesic drug O-Sulfation; C-S cleavage of acetaminophen-3-cysteine Acetaminophen sulfate and glucuronide Decreased activity or increased cellular toxicity Clostridium difficile 8, 45
Levamisole A typical anthelmintic drug that is also used for anti–colon cancer treatment Thiazole ring opening Formation of three thiazole ring-opened metabolites, namely, levametabol-I, II and III Increased activity Bacteroides and Clostridium spp. 46
Hespesidin Anti-allergic agent Deglycosylation Hesperetin Increased activity 47, 48
Glyceryl trinitrate Treatment for angina pectoris Denitration Glyceryl-1,3-dinitrate, glyceryl-1,2-dinitrate, glyceryl-1-mononitrate, and glyceryl-2-mononitrate Decreased activity 7
Methamphetamine Sympathomimetic stimulant Demethylation Amphetamine, norephedrine and an unknown metabolite Decreased activity Lactobacilli, Enterococci, and Clostridia 49
Nizatidine, Ranitidine H2-receptor antagonist for peptic ulcer disease therapy N-Oxide bond cleavage Decreased intestinal absorption and systemic bioavailability 50
Omeprazole Gastric ulcer Reduction Production of corresponding sulfide metabolites Decreased activity Anaerobic bacteria such as Bacteroides strains 51
Risperidone anti-psychotic drug Ring cleavage and hydroxylation Benzisoxazole ring scission or hydroxylation Inducting symptoms of Parkinson’s disease 52
Olsalazine Treatment for inflammatory diseases such as ulcerative colitis, Crohn’s disease and rheumatoid arthritis Azo reduction 5-aminosalicylclic acid Increased activity or causing side effects such as anorexia, nausea 53
Sulindac, Sulfinpyrazone Anti-inflammatory agent Reduction Formation of their sulfide products--sulindac sulfide, sulinpyrzone sulfide Increased activity 54
Chloramphenicol Antibacterial agent Amine formation and hydrolysis p-aminphenyl-2-amino-1, 3-propanediol Inducing bone marrow aplasia 55
Insulin Treatment for type 1 diabetes mellitus Proteolysis Peptides Decreased activity 56
Glycyrrhizin Anti-inflammation and hepatoprotective activity Hydrolysis 18-β-glycyrrhetinic acid Increased activity Eubacterium. sp. strain GLH 57, 58
Nitrazepam A hypnotic drug used in the treatment of moderate to severe insomnia Nitroreduction 7-aminonitrazepam Inducing teratogenicity 59
Flucytosine Antifungal drug Deamination 5-fluorouracil Increased activity or toxicity 60
Loperamide oxide Anti-diarrhea Reduction Loperamide Increased activity 61
Indomethacin Anti-inflammatory drug Deconjugation Dicreased activity, and increased side effects such as diarrhoea, anorexia, or weight loss 62
3,4-dihydroxyphenylalanine Treatment for Parkinson’s disease Dehydroxylation m-tyramine and m-hydroxylphenylacetic acid Increased activity 13
Sorivudine Antiviral drug Hydrolysis (E)-5-(2-bromovinyl)uracil (E)-5-(2-bromovinyl)uracil can inactivate a key liver enzyme, leadingto lethal toxicity of 5-fluorouracil when coadministered with 5-fluorouracil 13, 63
Lactulose Prebiotic Hydrolysis Monosaccharides Stimulating the growth of beneficial bacteria such as Bifidobacteria and Lactobacilli Utilized by Cronobacter sakazakii, Enterococcus casseliflavus, Enterococcus faecalis, and Klebsiella pneumoniae 62, 64
Baicalin An herbal extract with multiple biological functions such as anti-inflammation, prevention of diabetes mellitus, and anti-tumor effect Hydrolysis, deglycosylation Baicalein and oroxylin A Increased activity 4, 65, 66
Genistein An herbal extract with multiple biological functions such as prevention of obesity and type 2 diabetes Hydrogenation Production of 5-hydroxyequol via dihydrogenistein Bacteroides uniformis 67, 68
Ginsenoside Rb1 An herbal extract with multiple biolgocial functions such as anti-inflammation, and anti-tumor actions Hydrolysis Compound K Increased activity Bacteroides and Bifidobacterium 4, 69
Daidzein A phytoestrogen used for treatment hormone-dependent and age-related diseases, including osteoporosis, menopausal symptoms, cardiovascular diseases, and obesity Reduction, phenolic ring opening Dihydrodaidzein, equol, or O-desmethylanolensin(ODMA) Increased activity an Anaerobic Bacterium(Mt1B8); Enterolignans and Clostridium sp HGH 136 4, 67, 70
Quercetin-3-glucoside Protection against cardiovascular disease and tumors Deglycosylation Butyrate, acetate, 3,4-dihydroxyphenylacetic acid Eubacterium ramulus and Enterococcus casselilfavus 71
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2.2 Microbiota variation influences acetaminophen metabolism and acetaminophen-induced hepatotoxicity

Acetaminophen is a widely used analgesic and antipyretic medicine. However, the overdose of acetaminophen-induced hepatotoxicity is the most common cases in USA and UK 14, 15. Acetaminophen is deactivated mainly by glucuronidation and sulfation to conjugated metabolites, and a small part of acetaminophen could be transformed to N-acetyl-p-benzoquinone imine by P450 enzymes, which is supposed to be the toxic metabolite of acetaminophen. With metabolomics approach, Clayton et al. have observed that individuals with a high level of predose urinary p-cresol, a microbial metabolite 16, show low postdose urinary ratios of acetaminophen sulfate to acetaminophen glucuronide 8, suggesting the microbial contribution on acetaminophen metabolism. Moreover, Lee et al. evaluate the effects of intestinal microbiota on acetaminophen metabolism in antibiotic-treated rats. They find that antibiotic-treated rats have higher level of acetaminophen glutathione conjugates in blood than untreated rats 17, which further suggests the gut microbial impacts on acetaminophen metabolism. Since p-cresol and acetaminophen are competitive substrates for cytosolic sulfotransferase 18, the high level of p-cresol may compete with acetaminophen for binding with cytosolic sulfotransferase, and consequently alters the bioavailability of acetaminophen and its metabolites leading to the individual variation in acetaminophen metabolism and its hepatotoxicity. On the other hand, Possamai et al recently report that no significant differences in the extent of hepatocellular injury induced by acetaminophen between germ free and conventional housed mice. However, they observe that germ free mice show a milder acute liver failure and differential acetaminophen metabolism compared to conventional house mice 19, suggesting the variations in gut microbiota do not fully explain the differential susceptibility to acetaminophen-induced liver injury, at least in mice. Given the physiological differences between animals and human, the influence of gut microbial metabolism on acetaminophen-induced hepatotoxicity needs further investigation.

2.3 Microbial metabolism on digoxin

Digoxin is a cardiac glycoside which is used for chronic heart failure therapy. It is also a well-established drug that the cardiac activity of digoxin is influenced by gut microbial metabolism, which metabolizes the parent compound into inactive metabolite, dihydrodigoxin by reducing the lactone ring of digoxin 20,21. Additionally, the gut microbial metabolism of digoxin is further demonstrated by the observation that antibiotic pretreatment reduces the secretion of didydrodigoxin in urine and increases the level of digoxin in blood 22, as well as the identification of digoxin-metabolizing gut bacteria, Eggertherlla lenta 23. Recently, a further investigation reveals a cytochrome-encoding operon in a common gut bacteria Eggerthella lenta, which is transcriptionally activated by digoxin. The identified cytochrome-encoding operon, also named cardiac glycoside reductase (cgr) operon, is supposed to be a predictor of the inactivation of digoxin because a significant correlation between “cgr ratio” (cgr abundance normalized by E. lenta 16S rDNA level) and ex vivo digoxin inactivation in healthy volunteers is observed 9. Accordingly, the elucidation of the mechanisms underlying the gut microbial metabolism on digoxin augments the understanding on gut microbial impacts on pharmacokinetics, and paves the way for clinical application of reducing drug toxicity by manipulating gut microbiota.

1.4 Microbiota depletion reduces the side effect of irinotecan

Irinotecan (CPT-11) is a chemotherapeutic drug for colorectal cancers 24, which is intravenously used in clinic. CPT-11 is transformed by carboxylesterases in host tissues into active form SN-38, an inhibitor of topoisomerase I in tumor cells. SN-38 is conjugated into SN-38-G by hepatic UDP-glucuronosyltransferases before secreting into intestine. However, the nontoxic SN-38-G could be converted to SN-38 by the β-glucuronidase of gut bacteria leading to the severe intestinal side effect of diarrhea 25. Antibiotic treatment could significantly reduce the intestinal side effect of CPT-11 by suppressing the gut microbiota 26. Moreover, researchers have found out a potent inhibitor of β-glucuronidase that could effectively decrease the CPT-11-induced diarrhea and protect intestinal tissue by reducing cellular inflammation 27. Since CPT-11 is an intravenously delivered drug, the understanding on the gut microbial modulation on its intestinal side effect provides evidence of the profound impacts of gut microbiota on drug metabolism, in addition to the direct influence on orally administered drugs.

2. Gut microbiota influence on drug efficacy

Besides the well-evidenced microbial impacts on drug metabolism and toxicity, the intricate relationship between gut microbiota and host highlights the significance of gut microbiota on drug efficacy. In recent years, increasing evidence indicates that the variation of therapeutic effects of many drugs is associated with the differences in gut microbiota, which warrants the potential of gut microbiota-targeted manipulation for increasing drug efficacy.

3.1 Gut microbiota modulates the effect of antitumor chemotherapeutics

The commensal gut microbiota is profoundly involved in modulation of mammalian immunity 28. The antitumor chemotherapeutics usually cause the gut dysbiosis leading to severe intestinal side effects, as well as the modulation on host immune responses. Cyclophosphamide (CTX) is a widely used antitumor drug by inducing immunogenic cancer cell death 29, 30, subverting immunosuppressive T cells 31 and promoting TH 1 and TH17 cells control tumor cell growth32. Recently, researchers demonstrate that CTX can alter the composition of gut microbiota and induce the translocation of several species of Gram-positive bacteria into secondary lymphoid organs. Then, these bacteria stimulate the generation of a specific subset of “pathogenic” T helper17 (pTH17) cells and memory TH1 immune responses. Moreover, tumor-bearing germ free mice or mice treated with antibiotics to deplete Gram-positive bacteria show a reduction in pTH17 responses and resistance to the antitumor effect of CTX 33. In a similar study, researchers find that the disruption of gut microbiota impairs the therapeutic responses of subcutaneous tumors to a CpG-oligonucleotide immunotherapy and platinum chemotherapy. Meanwhile, germ free or antibiotic-treated mice show poor responses to therapy 34. As a result, the gut microbiota is also an important factor for influencing the efficacy of some antitumor chemotherapeutics, which highlights the potential of gut microbiota-targeted intervention for increasing the efficacy of antitumor chemotherapy.

3.2 Microbiota variation contributes to therapeutic difference of statin

Statins are the most frequently prescribed drugs for reducing plasma levels of LDL cholesterol and risk of cardiovascular disease by inhibiting 3-hydroxy-3-methyl-glutaryl-Co A (HMG-CoA) reductase 35. However, the efficacy of statins in reducing LDL-C varies greatly among individuals 36, whereas the reason is little known. Kaddurah-Daouk et al. investigate the correlation between baseline metabolites and therapeutic efficacy of simvastatin with targeted metabolomics 37. Their data indicate the baseline levels of several secondary bile acids, which are gut microbial-derived, could predict the magnitude of LDL-C lowering effect of simvastatin. Moreover, these microbial-derived secondary bile acids also correlate with the plasma levels of simvastatin, suggesting probable gut microbial impacts on the bioavailability of simvastatin. Similarly, a recent study indicates that incubation of lovastatin with human or rat fecalase preparations produces four metabolites. Moreover, the plasma concentration of the active hydroxyl acid metabolite of lovastatin is significantly lower in antibiotic-treated rats than controls 38. These results demonstrate that the oral lovastatin is also co-metabolized by gut microbiota, which may contribute to the variation in efficacy of lovastatin among individuals because of the differences in gut microbiota.

Expert opinion

Interindividual variation in response to same drug therapy is a very common phenomenon in clinic, which is predominantly regarded as a consequence of genetic diversity previously. However, the increasing evidence of gut microbiota involvement in drug metabolism shed light on the crucial roles of gut microbiota in determining the therapeutic outcomes in together with the host metabolism. Although we have made exciting progress in uncovering the intricate relationship between gut microbiota and drug metabolism during past decades, especially in the recent years because of technical innovation, there is still a long way to go before we can utilize the knowledge of gut microbiota for rational drug design, and personalized medicine, in which a more potent drug activity and lower drug-induced toxicity are expected. Currently, most of our endeavors are directing to the accumulation of knowledge on identification of roles and elucidation of mechanisms underlying the gut microbiota-involved drug metabolism and toxicity. Although the ultimate goal is prospective, there are some big challenges in front of us.

First, it is still a great challenge to identify the specific roles of gut bacteria in modulating drug metabolism. Antibiotic-treated animal models are frequently used for investigating the involvement of gut microbiota in drug metabolism and toxicity. Moreover, a more specific relationship between certain species of bacteria and drug metabolism can be discovered by using different antibiotics or their combination with different antibacterial spectrums. For example, vancomycin is usually used for elimination of Gram-positive bacteria, whereas a combination of ampicillin, neomycin, metronidazole and vancomycin is used for gut sterilization to produce a pseudo-germ free animal model 39. Compared to antibiotic-treated animal model, the germ free or gnotobiotic animals are better for investigating the contribution of specific bacteria in drug metabolism. However, both germ free and gnotobiotic animals are not only expensive, but also have strict requirements in animal house facilities, which greatly hinds their application. Accordingly, we envisage that antibiotic-treated animals will serve as a practical model for identifying the roles of gut microbiota in drug metabolism in most studies. However, more attention should be paid to distinguish the impacts on drug metabolism between antibiotic itself and antibiotic-induced alteration of gut microbiota. In addition, we should also bear in mind the existence of potential direct drug-drug interaction in intestine between unabsorbed antibiotics and investigated drugs, which may mislead our understanding on the role of gut microbiota in drug metabolism.

Second, the elucidation of gut microbial roles in drug metabolism largely relies on the technical innovations. The variable regions of bacteria 16S rDNA provide the opportunity for identification of bacteria species by 16S rDNA-based gene sequencing technique. However, the identification power of 16S rDNA-based gene sequencing is still very limited due to the extremely high similarity in sequence of 16S rDNA among bacteria within same family or even genus. Compared to the 16S rDNA sequencing, metagenomics is more powerful in microbial diversity study by providing unbiased sequence information of the whole gut microbiota. However, there is also limitation in application of metagenomics currently due to the relatively high price of sequencing and requirement of bioinformatics work on the enormous data of metagemomics. Therefore, other omics approach such as metabolomics is increasing adopted for combined analysis on gut microbiota-related metabolic profiling or targeted metabolic analysis of specific microbial-associated metabolic pathways. It is estimated at least 10% of metabolites in plasma are gut microbiota-related 40, in which more and more evidence has been achieved for bridging the gut microbiota-related metabolites with certain species of bacteria 41. As a result, it is prospective to investigate the role of gut microbiota in drug metabolism by using combined approaches such as metabolomics and metagenomics.

Third, the mechanisms underlying gut microbial modulation on drug metabolism are complicated and elusive. Currently, the effect of gut microbial-mediated drug metabolism has been well characterized in only about 40 clinical drugs. Given the thousands of clinical drugs, it is an urgent and challenging task for us to determine the roles of gut microbiota in drug metabolism and drug-induced toxicity. Moreover, the increasing application of antibiotics and their frequent combination with other medicines make the patients at the risk of unexpected drug-induced toxicity or compromising of drug efficacy. There are many ways for gut microbial modulation on drug metabolism such as direct secretion of drug metabolizing enzymes in intestine, completion for receptors or transporters in host tissues with drugs via production of bacterial metabolite, and microbial modulation on activity of drug metabolizing enzymes in host tissues which alters their capability in drug metabolism. Accordingly, the study on gut microbiota needs the efficient cooperation among scientists from different disciplines such as pharmacology, toxicology, microbiology, molecular biology, bioinformatics, and analytical chemistry, in addition to the instrumental innovation such as metagenomics and metabolomics. Based on the sustained enthusiasm on gut microbiota study and technical improvement, we believe that at least dozens of drugs which are co-metabolized by gut microbiota will be well-evidenced in the coming five to ten years, which will also facilitate the rational drug design by producing drugs with more potent and lower toxicity.

Article highlights.

  • The intricate gut microbiome is hypothesized as a “metabolic organ” within host. It is not only involved in many diseases development, but also plays critical roles in drug metabolism through microbiota-host cometabolism.

  • Currently, there are dozens of clinical drugs that have been demonstrated to be co-metabolized by host and gut microbiota. Nevertheless, the specific roles and mechanisms underlying gut microbial modulation on drug metabolism are still largely unexplored due to the complexity of gut microbiota itself and its relationship with host metabolism.

  • The interindividual variation of gut microbiota contributes to the therapeutic outcomes in clinic. The investigation of the gut microbial impacts on drug therapy provides novel evidence for gut microbial modulation on drug efficacy, which sheds light on the role of gut microbiota in personalized medicine.

  • The progress on gut microbiota study mainly relies on technical innovations. Metabolomics is an essential approach for investigating the involvement of gut microbiota in drug metabolism by discovering the gut microbial-related metabolites, in addition to the bacteria identification with metagenomics.

  • The mechanistic elucidation of gut microbiota in drug metabolism and toxicity will facilitate the rational drug design and provide important evidence for gut microbiota-targeted therapy.

Footnotes

Declaration of interest

Dr. Houkai Li was supported by the grants from The Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (No. A1-R140201) from Shanghai Municipal Education Commission, and Shanghai Pujiang Program (14PJD031) from the Science and Technology Commission of Shanghai Municipality.

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