1,626
Views
92
CrossRef citations to date
0
Altmetric
Reviews

The effect of gut microbiota on drug metabolism

, , , , , , , , , , PhD (Professor) & , PhD (Professor) show all
Pages 1295-1308 | Published online: 12 Jun 2013

Bibliography

  • Wienkers LC, Heath TG. Predicting in vivo drug interactions from in vitro drug discovery data. Nat Rev Drug Discov 2005;4:825-33
  • Williams JA, Hyland R, Jones BC, et al. Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos 2004;32:1201-8
  • Bjornsson TD, Callaghan JT, Einolf HJ, et al. The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. Drug Metab Dispos 2003;31:815-32
  • Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012;486:207-14
  • Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature 2012;486:222-7
  • Kang MJ, Ha HW, Kim GH, et al. Role of metabolism by intestinal bacteria in arbutin-induced suppression of lymphoproliferative response in vitro. Biomol Ther 2012;20:196-200
  • Larsen N, Vogensen FK, van den Berg FWJ, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 2010;5:e9085
  • Khanal T, Kim HG, Hwang YP, et al. Role of metabolism by the human intestinal microflora in arbutin-induced cytotoxicity in HepG2 cell cultures. Biochem Biophys Res Commun 2011;413:318-24
  • Khanal T, Kim HG, Choi JH, et al. Protective role of intestinal bacterial metabolism against baicalin-induced toxicity in HepG2 cell cultures. J Toxicol Sci 2012;37:363-71
  • Khanal T, Kim HG, Choi JH, et al. Biotransformation of geniposide by human intestinal microflora on cytotoxicity against HepG2 cells. Toxicol Lett 2012;209:246-54
  • Khanal T, Kim HG, Jin SW, et al. Protective role of metabolism by intestinal microflora in butyl paraben-induced toxicity in HepG2 cells cultures. Toxicol Lett 2012;213:174-83
  • Jeong HG, Kang MJ, Kim HG, et al. Role of intestinal microflora in xenobiotic-induced toxicity. Mol Nutr Food Res 2013;57:84-99
  • Sousa T, Paterson R, Moore V, et al. The gastrointestinal microbiota as a site for the biotransformation of drugs. Int J Pharm 2008;363:1-25
  • Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science 2001;292:1115-18
  • Saad R, Rizkallah MR, Aziz RK. Gut pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes. Gut Pathog 2012;4:16
  • Haiser HJ, Turnbaugh PJ. Developing a metagenomic view of xenobiotic metabolism. Pharmacol Res 2013;69:21-31
  • Yeo HK, Hyun YJ, Jang SE, et al. Development of fecal microbial enzyme mix for mutagenicity assay of natural products. J Microbiol Biotechnol 2012;22:838-48
  • Akao T, Che QM, Kobashi K, et al. A purgative action of barbaloin is induced by Eubacterium sp. strain BAR, a human intestinal anaerobe, capable of transforming barbaloin to aloe-emodin anthrone. Biol Pharm Bull 1996;19:136-8
  • Ishii Y, Tanizawa H, Takino Y. Studies of aloe. V. Mechanism of cathartic effect (4). Biol Pharm Bull 1994;17:651-3
  • Liu T, Jiang X. Investigation of the absorption mechanisms of baicalin and baicalein in rats. J Pharm Sci 2006;95:1326-33
  • Akao T, Kawabata K, Yanagisawa E, et al. Baicalin, the predominant flavone glucuronide of Scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form. J Pharm Pharmacol 2000;52:1563-8
  • Xing J, Chen X, Zhong D. Absorption and enterohepatic circulation of baicalin in rats. Life Sci 2005;78:140-6
  • Trinh HT, Joh EH, Kwak HY, et al. Anti-pruritic effect of baicalin and its metabolites, baicalein and oroxylin A, in mice. Acta Pharmacol Sin 2010;31:718-24
  • Jung MA, Jang SE, Hong SW, et al. The role of intestinal microflora in anti-inflammatory effect of baicalin in mice. Biomol Ther 2012;20:36-42
  • Zhang L, Lin G, Zuo Z. Involvement of UDP-glucuronosyltransferases in the extensive liver and intestinal first-pass metabolism of flavonoid baicalein. Pharm Res 2007;24:81-9
  • Chao JI, Su WC, Liu HF. Baicalein induces cancer cell death and proliferation retardation by the inhibition of CDC2 kinase and survivin associated with opposite role of p38 mitogen-activated protein kinase and AKT. Mol Cancer Ther 2007;6:3039-48
  • Gao Z, Huang K, Yang X, et al. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta 1999;1472:643-50
  • Dou W, Mukherjee S, Li H, et al. Alleviation of gut inflammation by Cdx2/Pxr pathway in a mouse model of chemical colitis. PLoS One 2012;7:1-13
  • Matthies A, Clavel T, Gütschow M, et al. Conversion of daidzein and genistein by an anaerobic bacterium newly isolated from the mouse intestine. Appl Environ Microbiol 2008;74:4847-52
  • Decroos K, Vanhemmens S, Cattoir S, et al. Isolation and characterisation of an equol-producing mixed microbial culture from a human faecal sample and its activity under gastrointestinal conditions. Arch Microbiol 2005;183:45-55
  • Bowey E, Adlercreutz H, Rowland I. Metabolism of isoflavones and lignans by the gut microflora: a study in germ-free and human flora associated rat. Food Chem Toxicol 2003;41:631-6
  • Kang NJ, Lee KW, Rogozin EA, et al. Equol, a metabolite of the soybean isoflavone daidzein, inhibits neoplastic cell transformation by targeting the MEK/ERK/p90RSK/activator protein-1 pathway. J Biol Chem 2007;282:32856-66
  • Liu X, Suzuki N, Santosh Laxmi YR, et al. Anti-breast cancer potential of daidzein in rodents. Life Sci 2012;91:415-19
  • Akao T, Kobashi K, Aburada M. Enzymic studies on the animal and intestinal bacterial metabolism of geniposide. Biol Pharm Bull 1994;17:1573-6
  • Kim BC, Kim HG, Lee SA, et al. Genipin-induced apoptosis in hepatoma cells is mediated by reactive oxygen species/c-Jun NH-terminal kinase-dependent activation of mitochondrial pathway. Biochem Pharmacol 2005;70:1398-407
  • Jin JS, Nishihata T, Kakiuchi N, et al. Biotransformation of C-glucosylisoflavone puerarin to estrogenic (3S)-equol in co-culture of two human intestinal bacteria. Biol Pharm Bull 2008;31:1621-5
  • Choi EJ, Kim T, Lee MS. Pro-apoptotic effect and cytotoxicity of genistein and genistin in human ovarian cancer SK-OV-3 cells. Life Sci 2007;80:1403-8
  • Leung KW, Wong AS. Pharmacology of ginsenosides: a literature review. Chin Med 2010;5:1-20
  • Wakabayashi C, Murakami K, Hasegawa H, et al. An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem Biophys Res Commun 1998;246:725-30
  • Bae EA, Shin JE, Kim DH. Metabolism of ginsenoside Re by human intestinal microflora and its estrogenic effect. Biol Pharm Bull 2005;28:1903-8
  • Kobashi K, Akao T. Relation of intestinal bacteria to pharmacological effects of glycosides. Biosci Microflora 1997;16:1-7
  • Akao T, Akao T, Hattori M, et al. Hydrolysis of glycyrrhizin to 18beta-glycyrrhetyl monoglucuronide by lysosomal beta-D-glucuronidase of animal livers. Biochem Pharmacol 1991;41:1025-9
  • Fujita H, Sakura T, Toyoshima S. Studies on the regulation by drugs against experimental hepatitis (1). The therapeutical effects of glycyrrhizinic acid, DL-methionine, their complex and tablets against acute injury induced by carbon tetrachloride or D-galactosamine. Oyo Yakuri 1978;16:637-45
  • Shim SB, Kim NJ, Kim DH. beta-Glucuronidase inhibitory activity and hepatoprotective effect of 18-glycyrrhetinic acid from the rhizomes of Glycyrrhiza uralensis. Planta Med 2000;66:40-3
  • Kim DH, Sohng IS, Kobashi K, et al. Purification and characterization of beta-glucosidase from Bacteroides JY-6, a human intestinal bacterium. Biol Pharm Bull 1996;19:1121-5
  • Labib S, Erb A, Kraus M, et al. The pig caecum model: a suitable tool to study the intestinal metabolism of flavonoids. Mol Nutr Food Res 2004;48:326-32
  • Roowi S, Mullen W, Edwards CA, et al. Yoghurt impacts on the excretion of phenolic acids derived from colonic breakdown of orange juice flavanones in humans. Mol Nutr Food Res 2009;53:68-75
  • Jin MJ, Kim U, Kim IS, et al. Effects of gut microflora on pharmacokinetics of hesperidin: a study on non-antibiotic and pseudo-germ-free rats. J Toxicol Environ Health A 2010;73:1441-50
  • Lee NK, Choi SH, Park SH, et al. Antiallergic activity of hesperidin is activated by intestinal microflora. Pharmacology 2004;71:174-80
  • Kim DH, Jung EA, Sohng IS, et al. Intestinal bacterial metabolism of flavonoids and its relation to some biological activities. Arch Pharm Res 1998;21:17-23
  • Shin JE, Bae EA, Lee YC, et al. Estrogenic effect of main components kakkalide and tectoridin of Puerariae flos and their metabolites. Biol Pharm Bull 2006;29:1202-6
  • Han YO, Han MJ, Park SH, et al. Protective effects of kakkalide from Flos Puerariae on ethanol-induced lethality and hepatic injury are dependent on its biotransformation by human intestinal microflora. J Pharmacol Sci 2003;93:331-6
  • Schoefer L, Mohan R, Schwiertz A, et al. Anaerobic degradation of flavonoids by Clostridium orbiscindens. Appl Environ Microbiol 2003;69:5849-54
  • Schneider H, Blaut M. Anaerobic degradation of flavonoids by Eubacterium ramulus. Arch Microbiol 2000;173:71-5
  • Jeon SM, Kim HK, Kim HJ, et al. Hypocholesterolemic and antioxidative effects of naringenin and its two metabolites in high-cholesterol fed rats. Transl Res 2007;149:15-21
  • Lee CH, Jeong TS, Choi YK, et al. Anti-atherogenic effect of citrus flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP-1 in high cholesterol-fed rabbits. Biochem Biophys Res Commun 2001;284:681-8
  • Kim DH, Bae EA, Han MJ. Anti-Helicobacter pylori activity of the metabolites of poncirin from Poncirus trifoliata by human intestinal bacteria. Biol Pharm Bull 1999;22:422-4
  • Kim JM, Shin JE, Bae EA, et al. Inhibitory effect of ponciretin on Helicobacter pylori VacA toxin-induced vacuolation in HeLa cells. J Microbiol Biotechnol 2006;16:46-51
  • Prasain JK, Jones K, Brissie N, et al. Identification of puerarin and its metabolites in rats by liquid chromatography-tandem mass spectrometry. J Agric Food Chem 2004;52:3708-12
  • Park EK, Shin J, Bae EA, et al. Intestinal bacteria activate estrogenic effect of main constituents puerarin and daidzin of Pueraria thunbergiana. Biol Pharm Bull 2006;29:2432-5
  • Choo MK, Park EK, Yoon HK, et al. Antithrombotic and antiallergic activities of daidzein, a metabolite of puerarin and daidzin produced by human intestinal microflora. Biol Pharm Bull 2002;25:1328-32
  • Lin YJ, Hou YC, Lin CH, et al. Puerariae radix isoflavones and their metabolites inhibit growth and induce apoptosis in breast cancer cells. Biochem Biophys Res Commun 2009;378:683-8
  • Park EK, Choo MK, Yoon HK, et al. Antithrombotic and antiallergic activities of rhaponticin from Rhei rhizoma are activated by human intestinal bacteria. Arch Pharm Res 2002;25:528-33
  • Chun YJ, Ryu SY, Jeong TC, et al. Mechanism-based inhibition of human cytochrome P450 1A1 by rhapontigenin. Drug Metab Dispos 2001;29:389-93
  • Yang J, Qian D, Jiang S, et al. Identification of rutin deglycosylated metabolites produced by human intestinal bacteria using UPLC–Q-TOF/MS. J Chromatogr B 2012;898:95-100
  • Guardia T, Rotelli AE, Juarez AO, et al. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco 2001;56:683-7
  • Chow JM, Shen SC, Huan SK, et al. Quercetin, but not rutin and quercitrin, prevention of H2O2-induced apoptosis via anti-oxidant activity and heme oxygenase 1 gene expression in macrophages. Biochem Pharmacol 2005;69:1839-51
  • Zhu JX, Wang Y, Kong LD, et al. Effects of Biota orientalis extract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver. J Ethnopharmacol 2004;93:133-40
  • Hattori M, Kim G, Motoike S, et al. Metabolism of sennosides by intestinal flora. Chem Pharm Bull (Tokyo) 1982;30:1338-46
  • Matsumoto M, Ishige A, Yazawa Y, et al. Promotion of intestinal peristalsis by Bifidobacterium spp. capable of hydrolysing sennosides in mice. PLoS One 2012;7:e31700
  • Choi JW, Shin KM, Park HJ, et al. Anti-inflammatory and anti-nociceptive effects of sinapyl alcohol and its glucoside syringin. Planta Med 2004;70:1027-32
  • Kim YP, Yamada M, Lim SS, et al. Inhibition by tectorigenin and tectoridin of prostaglandin E2 production and cyclooxgenase-2 induction in rat peritoneal macrophages. Biochim Biophys Acta 1999;1438:399-407
  • Han T, Cheng C, Liu Y, et al. In vitro evaluation of tectoridin, tectorigenin and tectorigenin sodium sulfonate on antioxidant properties. Food Chem Toxicol 2012;50:409-14
  • Lee SH, An JH, Lee HJ, et al. Evaluation of pharmacokinetic differences of acetaminophen in pseudo germ-free rats. Biopharm Drug Dispos 2012;33:292-303
  • Mikov M. The metabolism of drugs by the gut flora. Eur J Drug Metab Pharmacokinet 1994;19:201-7
  • Mikov M, Caldwell J, Dolphin CT, et al. The role of intestinal microflora in the formation of the methylthio adduct metabolites of paracetamol. Studies in neomycin-pretreated and germ-free mice. Biochem Pharmacol 1988;37:1445-9
  • Lindenbaum J, Rund DG, Butler VP Jr, et al. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N Engl J Med 1981;305:789-94
  • Saha JR, Butler VP Jr, Neu HC, et al. Digoxin-inactivating bacteria: identification in human gut flora. Science 1983;220:325-7
  • Mathan VI, Wiederman J, Dobkin JF, et al. Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora. Gut 1989;30:971-7
  • Goldin BR, Peppercorn MA, Goldman P. Contributions of host and intestinal flora in the metabolism of L-dopa by the rat. J Pharmacol Exp Ther 1973;186:160-6
  • Sandler M, Goodwin BL, Ruthven CR. Therapeutic implications in Parkinsonism of m-tyramine formation from L-dopa in man. Nature 1971;229:414-15
  • Sandler M, Karoum F, Ruthven CR, et al. m-Hydroxyphenylacetic acid formation from L-dopa in man: suppression by neomycin. Science 1969;166:1417-18
  • Harris BE, Manning BW, Federle TW, et al. Conversion of 5-fluorocytosine to 5-fluorouracil by human intestinal microflora. Antimicrob Agents Chemother 1986;29:44-8
  • Vermes A, Kuijper EJ, Guchelaar HJ, et al. An in vitro study on the active conversion of flucytosine to fluorouracil by microorganisms in the human intestinal microflora. Chemotherapy 2003;49:17-23
  • Vermes A, Guchelaar HJ, Van Kuilenburg AB, et al. 5-Fluorocytosine-related bone-marrow depression and conversion to fluorouracil: a pilot study. Fundam Clin Pharmacol 2002;16:39-47
  • Tobin P, Clarke S, Seale JP, et al. The in vitro metabolism of irinotecan (CPT-11) by carboxylesterase and beta-glucuronidase in human colorectal tumours. Br J Clin Pharmacol 2005;62:122-9
  • Wallace BD, Wang H, Lane KT, et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 2010;330:831-5
  • Stringer AM, Gibson RJ, Logan RM, et al. Faecal microflora and beta-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats. Cancer Biol Ther 2008;7:1919-25
  • Lavrijsen K, Van Dyck D, Van Houdt J, et al. Reduction of the prodrug loperamide oxide to its active drug loperamide in the gut of rats, dogs, and humans. Drug Metab Dispos 1995;23:354-62
  • Koch RL, Goldman P. The anaerobic metabolism of metronidazole forms N-(2-hydroxyethyl)-oxamic acid. J Pharmacol Exp Ther 1979;208:406-10
  • Rafii F, Wynne R, Heinze TM, et al. Mechanism of metronidazole-resistance by isolates of nitroreductase-producing Enterococcus gallinarum and Enterococcus casseliflavus from the human intestinal tract. FEMS Microbiol Lett 2003;225:195-200
  • Basit AW, Newton JM, Lacey LF. Susceptibility of the H2-receptor antagonists cimetidine, famotidine and nizatidine, to metabolism by the gastrointestinal microflora. Int J Pharm 2002;237:23-33
  • Chourasia MK, Jain SK. Pharmaceutical approaches to colon targeted drug delivery systems. J Pharm Pharm Sci 2003;6:33-66
  • Sandborn WJ, Hanauer SB. Systematic review: the pharmacokinetic profiles of oral mesalazine formulations and mesalazine pro-drugs used in management of ulcerative colitis. Aliment Pharmacol Ther 2003;17:29-42
  • Knoll U, Strauhs P, Schusser G, et al. Study of the plasma pharmacokinetics and faecal excretion of the prodrug olsalazine and its metabolites after oral administration to horses. J Vet Pharmacol Ther 2002;25:135-43
  • Ireland A, Priddle JD, Jewell DP. Comparison of 5-aminosalicylic acid and N-acetylaminosalicylic acid uptake by the isolated human colonic epithelial cell. Gut 1992;33:1343-7
  • Aura AM, Mattila I, Hyotylainen T, et al. Drug metabolome of the simvastatin formed by human intestinal microbiota in vitro. Mol Biosyst 2011;7:437-46
  • Kim DH, Hyun SH, Shim SB, et al. The role of intestinal bacteria in the transformation of sodium picosulfate. Jpn J Pharmacol 1992;59:1-5
  • Hoy SM, Scott LJ, Wagstaff AJ. Sodium picosulfate/magnesium citrate: a review of its use as a colorectal cleanser. Drugs 2009;69:123-36
  • Nakayama H, Kinouchi T, Kataoka K, et al. Intestinal anaerobic bacteria hydrolyse sorivudine, producing the high blood concentration of 5-(E)-(2-bromovinyl)uracil that increases the level and toxicity of 5-fluorouracil. Pharmacogenetics 1997;7:35-43
  • Okuda H, Ogura K, Kato A, et al. A possible mechanism of eighteen patient deaths caused by interactions of sorivudine, a new antiviral drug, with oral 5-fluorouracil prodrugs. J Pharmacol Exp Ther 1998;287:791-9
  • Ogura K, Nishiyama T, Takubo H, et al. Suicidal inactivation of human dihydropyrimidine dedydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine. Cancer Lett 1998;122:107-13
  • Renwick AG, Evans SP, Sweatman TW, et al. The role of the gut flora in the reduction of sulphinpyrazone in the rat. Biochem Pharmacol 1982;31:2649-56
  • Strong HA, Oates J, Sembi J, et al. Role of the gut flora in the reduction of sulfinpyrazone in humans. J Pharmacol Exp Ther 1984;230:726-32
  • Pay GF, Wallis RB, Zelaschi D. The effect of sulphinpyrazone and its metabolites on platelet function in vitro and ex vivo. Haemostasis 1981;10:165-75
  • Del Maschio A, Livio M, Cerletti C, et al. Inhibition of human platelet cyclo-oxygenase activity by sulfinpyrazone and three of its metabolites. Eur J Pharmacol 1984;101:209-14
  • Strong HA, Renwick AG, George CF, et al. The reduction of sulphinpyrazone and sulindac by intestinal bacteria. Xenobiotica 1987;17:685-96
  • Strong HA, Warner NJ, Renwick AG, et al. Sulindac metabolism: the importance of an intact colon. Clin Pharmacol Ther 1985;38:387-93
  • Duggan DE, Hooke KF, Risley EA, et al. Identification of the biologically active form of sulindac. J Pharmacol Exp Ther 1977;201:8-13
  • Available from: http://www.pharmgkb.org
  • Available from: http://ctdbase.org
  • Available from: http://www.pharmacomicrobiomics.com
  • Rizkallah MR, Saad R, Aziz RK. The Human Microbiome Project, personalized medicine, and the birth of pharmacomicrobiomics. Curr Pharmacogenomics Person Med 2010;8:182-93
  • Maurice CF, Haiser HJ, Turnbaugh PJ. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 2013;152:39-50
  • Thiele I, Heinken A, Fleming RMT. A systems biology approach to studying the role of microbes in human health. Curr Opin Biotechnol 2013;24:4-12
  • Heinken A, Sahoo S, Fleming RMT, et al. Systems-level characterization of a host-microbe metabolic symbiosis in the mammalian gut. Gut Microbes 2013;4:28-40
  • Meinl W, Sczesny S, Brigelius-Flohe R, et al. Impact of gut microbiota on intestinal and hepatic levels of phase 2 xenobiotic-metabolizing enzymes in the rat. Drug Metabol Dispos 2009;37:1179-86
  • Takasuna K, Hagiwara T, Hirohashi M, et al. Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride. Cancer Res 1996;56:3752-7

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.