The effect of gut microbiota on drug metabolism

Kang, Mi Jeong; Kim, Hyung Gyun; Kim, Jin Sung; Oh, Do Gyeong; Um, Yeon Ji; Seo, Chae Shin; Han, Ji Won; Cho, Hyun Ji; Kim, Ghee Hwan; Jeong, Tae Cheon; Jeong, Hye Gwang

doi:10.1517/17425255.2013.807798

Cited by 104 publications

(66 citation statements)

References 102 publications

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“…In addition, gut microbiota play an important role in drug metabolism. Although Bacteroidetes and Firmicutes are the two major families of gut microbiota [148] in mice, pigs, and humans, considerable interspecies variations have been found in their subclasses that were even more distinct in NHPs (Table 2). Interestingly, neither rodents nor rabbits are able to vomit, prohibiting the monitoring of novel compounds for this common side effect [149].…”

Section: Gastrointestinal Tract (Git)mentioning

confidence: 99%

Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research

Renner

Dobenecker²,

Blutke³

et al. 2016

Theriogenology

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Section: Gastrointestinal Tract (Git)mentioning

confidence: 99%

Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research

Renner

Dobenecker²,

Blutke³

et al. 2016

Theriogenology

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“…The ability of the gut microbiome to metabolize drugs was first recognized over 40 years back 44,45 . To date, dozens drugs and diet-derived bioactive compounds have been reported to undergo direct microbial modification [46][47][48][49] , and their number is still growing. in almost all cases, the exact mechanism, the specific reaction and the responsible microbial species remain unknown.…”

Section: Metabolism Of Xenobioticsmentioning

confidence: 99%

Human gut microbiota plays a role in the metabolism of drugs

Jourová¹,

Anzenbacher²,

Anzenbacherová³

2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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a Background and Aims. The gut microbiome, an aggregate genome of trillions of microorganisms residing in the human gastrointestinal tract, is now known to play a critical role in human health and predisposition to disease. It is also involved in the biotransformation of xenobiotics and several recent studies have shown that the gut microbiota can affect the pharmacokinetics of orally taken drugs with implications for their oral bioavailability. Methods. Review of Pubmed, Web of Science and Science Direct databases for the years 1957-2016. Results and Conclusions. Recent studies make it clear that the human gut microbiota can play a major role in the metabolism of xenobiotics and, the stability and oral bioavailability of drugs. Over the past 50 years, more than 30 drugs have been identified as a substrate for intestinal bacteria. Questions concerning the impact of the gut microbiota on drug metabolism, remain unanswered or only partially answered, namely (i) what are the molecular mechanisms and which bacterial species are involved? (ii) What is the impact of host genotype and environmental factors on the composition and function of the gut microbiota, (iii) To what extent is the composition of the intestinal microbiome stable, transmissible, and resilient to perturbation? (iv) Has past exposure to a given drug any impact on future microbial response, and, if so, for how long? Answering such questions should be an integral part of pharmaceutical research and personalised health care.

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“…There are significant challenges in the maintenance and use of germ-free animals (Gordon and Pesti, 1971). Pretreatment of animals with antibiotics can provide a temporary, almost complete microbe-free animal model (Sousa et al, 2008;Kang et al, 2013). This simpler pGF rat model was validated in our studies using a known probe for gut bacterial metabolism, hesperidin.…”

Section: Discussionmentioning

confidence: 85%

“…The enzymes responsible for reduction can be sensitive to the presence of oxygen, and as such, it was important to adopt appropriate in vitro conditions. An anaerobic chamber was instrumental to these studies (Finegold et al, 1983;Kang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Defining the Role of Gut Bacteria in the Metabolism of Deleobuvir: In Vitro and In Vivo Studies

et al. 2015

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Deleobuvir is a potent inhibitor of the hepatitis C virus nonstructural protein 5B polymerase. In humans, deleobuvir underwent extensive reduction to form CD 6168. This metabolite was not formed in vitro in aerobic incubations with human liver microsomes or cytosol. Anaerobic incubations of deleobuvir with rat and human fecal homogenates produced CD 6168. Using these in vitro formation rates, a retrospective analysis was conducted to assess whether the fecal formation of CD 6168 could account for the in vivo levels of this metabolite. The formation of CD 6168 was also investigated using a pseudo-germ free (pGF) rat model, in which gut microbiota were largely eradicated by antibiotic treatment. Plasma exposure (area under the curve from 0 to ') of CD 6168 was approximately 9-fold lower in pGF rats (146 6 64 ng·h/ml) compared with control rats (1,312 6 649 ng·h/ml). Similarly, in pGF rats, lower levels of CD 6168 (1.5% of the deleobuvir dose) were excreted in feces compared with control rats (42% of the deleobuvir dose). In agreement with these findings, in pGF rats, approximately all of the deleobuvir dose was excreted as deleobuvir into feces (105% of dose), whereas only 26% of the deleobuvir dose was excreted as deleobuvir in control rats. These differences in plasma and excretion profiles between pGF and control rats confirm the role of gut bacteria in the formation of CD 6168. These results underline the importance of evaluating metabolism by gut bacteria and highlight experimental approaches for nonclinical assessment of bacterial metabolism in drug development.

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The effect of gut microbiota on drug metabolism

Cited by 104 publications

References 102 publications

Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research

Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research

Human gut microbiota plays a role in the metabolism of drugs

Defining the Role of Gut Bacteria in the Metabolism of Deleobuvir: In Vitro and In Vivo Studies

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