The metabolic effect of gut microbiota on drugs

References

• Adlercreutz H, Martin F. 1980. Biliary excretion and intestinal metabolism of progesterone and estrogens in man. J Steroid Biochem. 13:231–244.
   PubMedGoogle Scholar
• Akao T, Che QM, Kobashi K, Hattori M, Namba T. 1996. 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. 19:136–138.
   PubMed Web of Science ®Google Scholar
• Akao T, Akao T, Hattori M, Kanaoka M, Yamamoto K, Namba T, Kobashi K. 1991. Hydrolysis of glycyrrhizin to 18 beta-glycyrrhetyl monoglucuronide by lysosomal beta-D-glucuronidase of animal livers. Biochem Pharmacol. 41:1025–1029.
   PubMed Web of Science ®Google Scholar
• Akyildiz BN, Kurtoğlu S, Kondolot M, Tunç A. 2010. Cyanide poisoning caused by ingestion of apricot seeds. Ann Trop Paediatr. 30:39–43.
   PubMed Web of Science ®Google Scholar
• Antila S, Pesonen U, Lehtonen L, Tapanainen P, Nikkanen H, Vaahtera K, Scheinin H. 2004. Pharmacokinetics of levosimendan and its active metabolite OR-1896 in rapid and slow acetylators. Eur J Pharm Sci. 23:213–222.
   PubMed Web of Science ®Google Scholar
• Bachrach WH. 1988. Sulfasalazine: I. An historical perspective. Am J Gastroenterol. 83:487–496.
   PubMed Web of Science ®Google Scholar
• Bae EA, Han MJ, Choo MK, Park SY, Kim DH. 2002. Metabolism of 20 (S)- and 20 (R)-ginsenoside Rg3 by human intestinal bacteria and its relation to in vitro biological activities. Biol Pharm Bull. 25:58–63.
   PubMed Web of Science ®Google Scholar
• Bae EA, Shin JE, Kim DH. 2005. Metabolism of ginsenoside re by human intestinal microflora and its estrogenic effect. Biol Pharm Bull. 28:1903–1908.
   PubMed Web of Science ®Google Scholar
• Bakke OM. 1971. Degradation of DOPA by intestinal microorganisms in vitro. Acta Pharmacol Toxicol. 30:115–121.
   PubMedGoogle Scholar
• Basit AW, Lacey LF. 2001. Colonic metabolism of ranitidine; implications for its delivery and absorption. Int J Pharm. 227:157–165.
   PubMed Web of Science ®Google Scholar
• Basit AW, Newton JM, Lacey LF. 2002. Susceptibility of the H2-receptor antagonists cimetidine, famotidine and nizatidine, to metabolism by the gastrointestinal microflora. Int J Pharm. 237:23–33.
   PubMed Web of Science ®Google Scholar
• Bowey E, Adlercreutz H, Rowland I. 2003. Metabolism of isoflavones and lignans by the gut microflora: a study in germ-free and human flora associated rats. Food Chem Toxicol. 41:631–636.
   PubMed Web of Science ®Google Scholar
• Calne DB, Karoum F, Ruthven CR, Sandler M. 1969. The metabolism of orally administered l-DOPA in Parkinsonism. Br J Pharmacol. 37:57–68.
   PubMed Web of Science ®Google Scholar
• Carter JH, McLafferty MA, Goldman P. 1980. Role of the gastrointestinal microflora in amygdalin (laetrile)-induced cyanide toxicity. Biochem Pharmacol. 29:301–304.
   PubMed Web of Science ®Google Scholar
• Chan RP, Pope DJ, Gilbert AP, Sacra PJ, Baron JH, Lennard-Jones JE. 1983. Studies of two novel sulfasalazine analogs, ispsalazide and balsalazide. Digest Dis Sci. 28:609–615.
   PubMed Web of Science ®Google Scholar
• Chang HK, Yang HY, Lee TH, Shin MC, Lee MH, Shin MS, Kim CJ, Kim OJ, Hong SP, Cho S. 2005. Armeniacae semen extract suppresses lipopolysaccharide-induced expressions of cycloosygenase-2 and inducible nitric oxide synthase in mouse BV2 microglial cells. Biol Pharm Bull. 28:449–454.
   PubMed Web of Science ®Google Scholar
• Choi J, Shin KM, Park HJ, Jung HJ, Kim HJ, Lee YS, Rew JH, Lee KT. 2004. Anti-inflammatory and antinociceptive effects of sinapyl alcohol and its glucoside syringin. Planta Med. 70:1027–1032.
   PubMed Web of Science ®Google Scholar
• Choo MK, Park EK, Yoon HK, Kim DH. 2002. Antithrombotic and antiallergic activities of daidzein, a metabolite of puerarin and daidzin produced by human intestinal microflora. Biol Pharm Bull. 25:1328–1332.
   PubMed Web of Science ®Google Scholar
• Chow JM, Shen SC, Huan SK, Lin HY, Chen YC. 2005. 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. 69:1839–1851.
   PubMed Web of Science ®Google Scholar
• Conlon MA, Bird AR. 2014. The impact of diet and lifestyle on gut microbiota and human health. Nutrients. 7:17–44.
   PubMed Web of Science ®Google Scholar
• Decroos K, Vanhemmens S, Cattoir S, Boon N, Verstraete W. 2005. Isolation and characterisation of an equol-producing mixed microbial culture from a human faecal sample and its activity under gastrointestinal conditions. Arch Microbiol. 183:45–55.
   PubMed Web of Science ®Google Scholar
• Deloménie C, Fouix S, Longuemaux S, Brahimi N, Bizet C, Picard B, Denamur E, Dupret JM. 2001. Identification and functional characterization of arylamine N-acetyltransferases in eubacteria: evidence for highly selective acetylation of 5-aminosalicylic acid. J Bacteriol. 183:3417–3427.
   PubMed Web of Science ®Google Scholar
• Deng Y, Rogers M, Sychterz C, Talley K, Qian Y, Bershas D, Ho M, Shi W, Chen EP, Serabjit-Singh C, et al. 2011. Investigations of hydrazine cleavage of eltrombopag in humans. Drug Metab Dispos. 39:1747–1754.
   PubMed Web of Science ®Google Scholar
• Dethlefsen L, Relman DA. 2011. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci USA. 108:4554–4561.
   PubMed Web of Science ®Google Scholar
• Dobkin JF, Saha JR, Butler VP Jr, Neu HC, Lindenbaum J. 1982. Inactivation of digoxin by Eubacterium lentum, an anaerobe of the human gut flora. Trans Assoc Am Physicians. 95:22–29.
   PubMedGoogle Scholar
• Dull BJ, Salata K, Goldman P. 1987. Role of the intestinal flora in the acetylation of sulfasalazine metabolites. Biochem Pharmacol. 36:3772–3774.
   PubMed Web of Science ®Google Scholar
• Elkington SG, Floch MH, Conn HO. 1969. Lactulose in the treatment of chronic portal-systemic encephalopathy. N Engl J Med. 281:408–412.
   PubMed Web of Science ®Google Scholar
• Elmer GW, Remmel RP. 1984. Role of intestinal microflora in clonazepam metabolism in the rat. Xenobiotica. 14:829–840.
   PubMed Web of Science ®Google Scholar
• Enright EF, Joyce SA, Gahan CGM, Griffin BT. 2017. Impact of gut microbiota-mediated bile acid metabolism on the solubilization capacity of bile salt micelles and drug solubility. Mol Pharm. 14:1251–1263.
   PubMed Web of Science ®Google Scholar
• Filippo CD, Cavalieri D, Paola MD, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P. 2010. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 107:14691–14696.
   PubMed Web of Science ®Google Scholar
• Fouts JR, Kamm JJ, Brodie BB. 1957. Enzymatic reduction of prontosil and other azo dyes. J Pharmacol Exp Ther. 120:291–300.
   PubMed Web of Science ®Google Scholar
• Fujii J, Inotsume N, Nakano M. 1987. Degradation of bromazepam by the intestinal microflora. Chem Pharm Bull. 35:4338–4341.
   PubMed Web of Science ®Google Scholar
• Fuller AT. 1937. Is p-aminobenzene sulphonamide the active agent in prontosil therapy? Lancet. 229:194–198.
   Google Scholar
• Gingell R, Bridges JW. 1973. Intestinal azo-reduction and glucuronide conjugation of prontosil. Xenobiotica. 3:599–604.
   PubMed Web of Science ®Google Scholar
• Gingell R, Bridges JW, Williams RT. 1971. The role of the gut flora in the metabolism of prontosil and neoprontasil in the rat. Xenobiotica. 1:143–156.
   PubMedGoogle Scholar
• Goodman AL, McNulty NP, Zhao Y, Leip D, Mitra RD, Lozupone CA, Knight R, Gordon JI. 2009. Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe. 6:279–289.
   PubMed Web of Science ®Google Scholar
• Guardia T, Rotelli AE, Juarez AO, Pelzer LE. 2001. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco. 56:683–687.
   PubMedGoogle Scholar
• Han T, Cheng G, Liu Y, Yang H, Hu YT, Huang W. 2012. In vitro evaluation of tectoridin, tectorigenin and tectorigenin sodium sulfonate on antioxidant properties. Food Chem Toxicol. 50:409–414.
   PubMed Web of Science ®Google Scholar
• Han YO, Han MJ, Park SH, Kim DH. 2003. 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. 93:331–336.
   PubMed Web of Science ®Google Scholar
• Harris BE, Manning BW, Federle TW, Diasio RB. 1986. Conversion of 5-fluorocytosine to 5-fluorouracil by human intestinal microflora. Antimicrob Agents Chemother. 29:44–48.
   PubMed Web of Science ®Google Scholar
• Hashim H, Azmin S, Razlan H, Yahya NW, Tan HJ, Manaf MRA, Ibrahim NM. 2014. Eradication of Helicobacter pylori infection improves levodopa action, clinical symptoms and quality of life in patients with Parkinson’s disease. PLoS One. 9:e112330.
   PubMed Web of Science ®Google Scholar
• Hattori M, Kim G, Motoike S, Kobashi K, Namba T. 1982. Metabolism of sennosides by intestinal flora. Chem Pharm Bull. 30:1338–1346.
   PubMed Web of Science ®Google Scholar
• Hayllar J, Bjarnason I. 1991. Sulphasalazine in ulcerative colitis: in memoriam? Gut. 32:462–463.
   PubMed Web of Science ®Google Scholar
• Holt R. 1967. The bacterial degradation of chloramphenicol. Lancet. 1:1259–1260.
   PubMed Web of Science ®Google Scholar
• Human Microbiome Project Consortium. 2012. Structure, function and diversity of the healthy human microbiome. Nature. 486:207–214.
   PubMed Web of Science ®Google Scholar
• Jensen KF, Nygaard P. 1975. Purine nucleoside phosphorylase from Escherichia coli and Salmonella typhimurium. Purification and some properties. Eur J Biochem. 51:253–265.
   PubMedGoogle Scholar
• Jeon SM, Kim HK, Kim HJ, Do GM, Jeong TS, Park YB, Choi MS. 2007. Hypocholesterolemic and antioxidative effects of naringenin and its two metabolites in high-cholesterol fed rats. Transl Res. 149:15–21.
   PubMed Web of Science ®Google Scholar
• Jernberg C, Löfmark S, Edlund C, Jansson JK. 2010. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology. 156:3216–3223.
   PubMed Web of Science ®Google Scholar
• Jia W, Xie G, Jia W. 2018. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol. 15:111–128.
   PubMed Web of Science ®Google Scholar
• Jin MJ, Kim U, Kim IS, Kim Y, Kim DH, Han SB, Kim DH, Kwon OS, Yoo HH. 2010. Effects of gut microflora on pharmacokinetics of hesperidin: a study on non-antibiotic and pseudo-germ-free rats. J Toxicol Environ Health Part A. 73:1441–1450.
   PubMed Web of Science ®Google Scholar
• Kang MJ, Kim HG, Kim JS, Oh DG, Um YJ, Seo CS, Han JW, Cho HJ, Kim GH, Jeong TC, et al. 2013. The effect of gut microbiota on drug metabolism. Exp Opin Drug Metab Toxicol. 9:1295–1308.
   PubMed Web of Science ®Google Scholar
• Kang NJ, Lee KW, Rogozin EA, Cho YY, Heo YS, Bode AM, Lee HJ, Dong Z. 2007. 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. 282:32856–32866.
   PubMed Web of Science ®Google Scholar
• Kim DH, Hyun SH, Shim SB, Kobashi K. 1992. The role of intestinal bacteria in the transformation of sodium picosulfate. Jpn J Pharmacol. 59:1–5.
   PubMedGoogle Scholar
• Kim DH, Jung EA, Sohng IS, Han JA, Kim TH, Han MJ. 1998. Intestinal bacterial metabolism of flavonoids and its relation to some biological activities. Arch Pharm Res. 21:17–23.
   PubMed Web of Science ®Google Scholar
• Kim DH, Sohng IS, Kobashi K, Han MJ. 1996. Purification and characterization of beta-glucosidase from Bacteroides JY-6, a human intestinal bacterium. Biol Pharm Bull. 19:1121–1125.
   PubMed Web of Science ®Google Scholar
• Kim YP, Yamada M, Lim SS, Lee SH, Ryu N, Shin KH, Ohuchi K. 1999. Inhibition by tectorigenin and tectoridin of prostaglandin E2 production and cyclooxgenase-2 induction in rat peritoneal macrophages. Biochim Biophys Acta. 1438:399–407.
   PubMed Web of Science ®Google Scholar
• Kitamura S, Sugihara K, Kuwasako M, Tatsumi K. 1997. The role of mammalian intestinal bacteria in the reductive metabolism of zonisamide. J Pharm Pharmacol. 49:253–256.
   PubMed Web of Science ®Google Scholar
• Klaassen CD, Cui JY. 2015. Review: mechanisms of how the intestinal microbiota alters the effects of drugs and bile acids. Drug Metab Dispos. 43:1505–1521.
   PubMed Web of Science ®Google Scholar
• Koch RL, Beaulieu BB Jr, Goldman P. 1980. Role of the intestinal flora in the metabolism of misonidazole. Biochem Pharmacol. 29:3281–3284.
   PubMed Web of Science ®Google Scholar
• Koch RL, Chrystal EJ, Beaulieu BB, Goldman P. 1979. Acetamide—a metabolite of metronidazole formed by the intestinal flora. Biochem Pharmacol. 28:3611–3615.
   PubMed Web of Science ®Google Scholar
• Koch RL, Goldman P. 1979. The anaerobic metabolism of metronidazole forms N-(2-hydroxyethyl)-oxamic acid. J Pharmacol Exp Ther. 208:406–410.
   PubMed Web of Science ®Google Scholar
• Kodawara T, Higashi T, Negoro Y, Kamitani Y, Igarashi T, Watanabe K, Tsukamoto H, Yano R, Masada M, Iwasaki H, et al. 2016. The inhibitory effect of ciprofloxacin on the β-glucuronidase-mediated deconjugation of the irinotecan metabolite SN-38-G. Basic Clin Pharmacol Toxicol. 118:333–337.
   PubMed Web of Science ®Google Scholar
• Koppel N, Rekdal VM, Balskus EP. 2017. Chemical transformation of xenobiotics by the human gut microbiota. Science. 356:eaag2770.
   PubMed Web of Science ®Google Scholar
• Labib S, Erb A, Kraus M, Wickert T, Richling E. 2004. The pig caecum model: a suitable tool to study the intestinal metabolism of flavonoids. Mol Nutr Food Res. 48:326–332.
   PubMed Web of Science ®Google Scholar
• Lavrijsen K, Van Dyck D, Van Houdt J, Hendrickx J, Monbaliu J, Woestenborghs R, Meuldermans W, Heykants J. 1995. Reduction of the prodrug loperamide oxide to its active drug loperamide in the gut of rats, dogs, and humans. Drug Metab Dispos. 23:354–362.
   PubMed Web of Science ®Google Scholar
• Lee NK, Choi SH, Park SH, Park EK, Kim DH. 2004. Antiallergic activity of hesperidin is activated by intestinal microflora. Pharmacology. 71:174–180.
   PubMed Web of Science ®Google Scholar
• Lee CH, Jeong TS, Choi YK, Hyun BH, Oh GT, Kim EH, Kim JR, Han JI, Bok SH. 2001. 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. 284:681–688.
   PubMed Web of Science ®Google Scholar
• Lee J, Lee E, Kim D, Lee J, Yoo J, Koh B. 2009. Studies on absorption, distribution and metabolism of ginseng in humans after oral administration. J Ethnopharmacol. 122:143–148.
   PubMed Web of Science ®Google Scholar
• Leung KW, Wong AS. 2010. Pharmacology of ginsenosides: a literature review. Chin Med. 5:20.
   PubMedGoogle Scholar
• Lin YJ, Hou YC, Lin CH, Hsu YA, Sheu JJC, Lai CH, Chen BH, Chao PDL, Wan L, Tsai FJ. 2009. Puerariae radix isoflavones and their metabolites inhibit growth and induce apoptosis in breast cancer cells. Biochem Biophys Res Commun. 378:683–688.
   PubMed Web of Science ®Google Scholar
• Lindenbaum J, Rund DG, Butler VP Jr, Tse-Eng D, Saha JR. 1981. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N Engl J Med. 305:789–794.
   PubMed Web of Science ®Google Scholar
• Liu X, Suzuki N, Laxmi YRS, Okamoto Y, Shibutani S. 2012. Anti-breast cancer potential of daidzein in rodents. Life Sci. 91:415–419.
   PubMed Web of Science ®Google Scholar
• Magnusson JO, Bergdahl B, Bogentoft C, Jonsson UE. 1982. Metabolism of digoxin and absorption site. Br J Clin Pharmacol. 14:284–285.
   PubMed Web of Science ®Google Scholar
• Mathan VI, Wiederman J, Dobkin JF, Lindenbaum J. 1989. Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora. Gut. 30:971–977.
   PubMed Web of Science ®Google Scholar
• Matsumoto M, Ishige A, Yazawa Y, Kondo M, Muramatsu K, Watanabe K. 2012. Promotion of intestinal peristalsis by Bifidobacterium spp. capable of hydrolysing sennosides in mice. PLoS One. 7:e31700.
   PubMed Web of Science ®Google Scholar
• Matthies A, Clavel T, Gutschow M, Engst W, Haller D, Blaut M, Braune A. 2008. Conversion of daidzein and genistein by an anaerobic bacterium newly isolated from the mouse intestine. Appl Environ Microbiol. 74:4847–4852.
   PubMed Web of Science ®Google Scholar
• Meuldermans W, Hendrickx J, Mannens G, Lavrijsen K, Janssen C, Bracke J, Le Jeune L, Lauwers W, Heykants J. 1994. The metabolism and excretion of risperidone after oral administration in rats and dogs. Drug Metab Dispos. 22:129–138.
   PubMed Web of Science ®Google Scholar
• Nakayama H, Kinouchi T, Kataoka K, Akimoto S, Matsuda Y, Ohnishi Y. 1997. 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. 7:35–43.
   PubMedGoogle Scholar
• Noh K, Kang YR, Nepal MR, Shakya R, Kang MJ, Kang W, Lee S, Jeong HG, Jeong TC. 2017. Impact of gut microbiota on drug metabolism: an update for safe and effective use of drugs. Arch Pharm Res. 40:1345–1355.
   PubMed Web of Science ®Google Scholar
• Nose M, Ito M, Kamimura K, Shimizu M, Ogihara Y. 1994. A Comparison of antihepatotoxic activity between glycyrrhizin and glycyeehinic acid. Planta Med. 60:136–139.
   PubMed Web of Science ®Google Scholar
• Okuda H, Ogura K, Kato A, Takubo H, Watabe T. 1998. 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. 287:791–799.
   PubMed Web of Science ®Google Scholar
• Orme M L, Back D J. 1990. Factors affecting the enterohepatic circulation of oral contraceptive steroids. Am J Obstet Gynecol. 163:2146–2152.
   PubMed Web of Science ®Google Scholar
• Park EK, Shin J, Bae EA, Lee YC, Kim DH. 2006. Intestinal bacteria activate estrogenic effect of main constituents puerarin and daidzin of Pueraria thunbergiana. Biol Pharm Bull. 29:2432–2435.
   PubMed Web of Science ®Google Scholar
• Peppercorn MA, Goldman P. 1973. Distribution studies of salicylazosulfapyridine and its metabolites. Gastroenterology. 64:240–245.
   PubMed Web of Science ®Google Scholar
• Rafii F, Sutherland JB, Hansen EB Jr, Cerniglia CE. 1997. Reduction of nitrazepam by clostridium leptum, a nitroreductase-producing bacterium isolated from the human intestinal tract. Clin Infect Dis. 25:S121–S122.
   PubMed Web of Science ®Google Scholar
• Roowi S, Mullen W, Edwards CA, Crozier A. 2009. Yoghurt impacts on the excretion of phenolic acids derived from colonic breakdown of orange juice flavanones in humans. Mol Nutr Food Res. 53:S68–S75.
   PubMed Web of Science ®Google Scholar
• Saha JR, Butler VP Jr, Neu HC, Lindenbaum J. 1983. Digoxin-inactivating bacteria: identification in human gut flora. Science. 220:325–327.
   PubMed Web of Science ®Google Scholar
• Sandler M, Goodwin B. L, Ruthven C. R. J, Calne D. B. 1971. Therapeutic implications in Parkinsonism of m-tyramine formation from L-dopa in man. Nature. 229:414–415.
   PubMed Web of Science ®Google Scholar
• Sasahara K, Nitanai T, Habara T, Kojima T, Kawahara Y, Morioka T, Nakajima E. 1981. Dosage form design for mprovement of bioavailability of levodopa IV: possible causes of low bioavailability of oral levodopa in dogs. J Pharm Sci. 70:730–733.
   PubMed Web of Science ®Google Scholar
• Sasaki I, Tamura T, Shibakawa T, Fujita T, Murakami M, Yamamoto A, Muranishi S. 1997. Metabolism of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, by intestinal microorganisms. Pharm Res. 14:1004–1007.
   PubMed Web of Science ®Google Scholar
• Sasaki I, Tozaki H, Matsumoto K, Ito Y, Fujita T, Murakami M, Muranishi S, Yamamoto A. 1999. Development of an oral formulation of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, using n-lauryl-beta-D-maltopyranoside as an absorption enhancer. Biol Pharm Bull. 22:611–615.
   PubMed Web of Science ®Google Scholar
• Satoh T, Hosokawa M. 1998. The mammalian carboxylesterases: from molecules to functions. Annu Rev Pharmacol Toxicol. 38:257–288.
   PubMed Web of Science ®Google Scholar
• Scarmeas N, Stern Y, Mayeux R, Luchsinger JA. 2006. Mediterranean diet, Alzheimer disease, and vascular mediation. Arch Neurol. 63:1709–1717.
   PubMed Web of Science ®Google Scholar
• Schroder H, Gustafsson BE. 1973. Azo reduction of salicyl-azosulphapyridine in germ free and conventional rats. Xenobiotica. 3:225–231.
   PubMed Web of Science ®Google Scholar
• Shamat MA. 1993. The role of the gastrointestinal microflora in the metabolism of drugs. Int J Pharm. 97:1–13.
   Web of Science ®Google Scholar
• Sheldon P.W, Clarke C, Dawson K.B, Simpson W, Simmons D.J.C. 1984. Intestinal microflora as potential modifiers of sensitizer activity in vivo. Int J Radiat Oncol Biol Phys. 10:1371–1375.
   PubMed Web of Science ®Google Scholar
• Shim SB, Kim NJ, Kim DH. 2000. beta-Glucuronidase inhibitory activity and hepatoprotective effect of 18-glycyrrhetinic acid from the rhizomes of Glycyrrhiza uralensis. Planta Med. 66:40–43.
   PubMed Web of Science ®Google Scholar
• Shin J, Bae EA, Lee YC, Ma JY, Kim DH. 2006. Estrogenic effect of main components kakkalide and tectoridin of Puerariae flos and their metabolites. Biol Pharm Bull. 29:1202–1206.
   PubMed Web of Science ®Google Scholar
• Shu YZ, Kingston DG, Van Tassell RL, Wilkins TD. 1991. Metabolism of levamisole, an anti-colon cancer drug, by human intestinal bacteria. Xenobiotica. 21:737–750.
   PubMed Web of Science ®Google Scholar
• Simon GL, Gorbach SL. 1984. Intestinal flora in health and disease. Gastroenterology. 86:174–193.
   PubMed Web of Science ®Google Scholar
• Smith GE, Griffiths LA. 1974. Metabolism of n-acetylated and o-alkylated drugs by the intestinal microflora during anaerobic incubation in vitro. Xenobiotica. 4:477–487.
   PubMed Web of Science ®Google Scholar
• Sousa T, Paterson R, Moore V, Carlsson A, Abrahamsson B, Basit AW. 2008. The gastrointestinal microbiota as a site for the biotransformation of drugs. Int J Pharm. 363:1–25.
   PubMed Web of Science ®Google Scholar
• Strong HA, Renwick AG, George CF, Liu YF, Hill MJ. 1987. The reduction of sulphinpyrazone and sulindac by intestinal bacteria. Xenobiotica. 17:685–696.
   PubMed Web of Science ®Google Scholar
• Svartz N. 1988. Sulfasalazine: II. Some notes on the discovery and development of salazopyrin. Am J Gastroenterol. 83:497–503.
   PubMed Web of Science ®Google Scholar
• Takasuna K, Hagiwara T, Hirohashi M, Kato M, Nomura M, Nagai E, Yokoi T, Kamataki T. 1998. Inhibition of intestinal microflora beta-glucuronidase modifies the distribution of the active metabolite of the antitumor agent, irinotecan hydrochloride (CPT-11) in rats. Cancer Chemother Pharmacol. 42:280–286.
   PubMed Web of Science ®Google Scholar
• Takasuna K, Hagiwara T, Watanabe K, Onose S, Yoshida S, Kumazawa E, Nagai E, Kamataki T. 2006. Optimal antidiarrhea treatment for antitumor agent irinotecan hydrochloride (CPT-11)-induced delayed diarrhea. Cancer Chemother Pharmacol. 58:494–503.
   PubMed Web of Science ®Google Scholar
• Takeno S, Hirano Y, Kitamura A, Sakai T. 1993. Comparative development toxicity and metabolism of nitrazepam in rats and mice. Toxicol Appl Pharmacol. 121:233–238.
   PubMed Web of Science ®Google Scholar
• Takeno S, Sakai T. 1991. Involvement of the intestinal microflora in nitrazepam-induced teratogenicity in rats and its relationship to nitroreduction. Teratology. 44:209–214.
   PubMedGoogle Scholar
• Tozaki H, Emi Y, Horisaka E, Fujita T, Yamamoto A, Muranishi S. 1995. Metabolism of peptide drugs by the microorganisms in rat cecal contents. Biol Pharm Bull. 18:929–931.
   PubMed Web of Science ®Google Scholar
• Tozaki H, Emi Y, Horisaka E, Fujita T, Yamamoto A, Muranishi S. 1997. Degradation of insulin and calcitonin and their protection by various protease inhibitors in rat caecal contents: implications in peptide delivery to the colon. J Pharm Pharmacol. 49:164–168.
   PubMed Web of Science ®Google Scholar
• Trinh HT, Joh EH, Kwak HY, Baek NI, Kim DH. 2010. Anti-pruritic effect of baicalin and its metabolites, baicalein and oroxylin A, in mice. Acta Pharmacol Sin. 31:718–724.
   PubMed Web of Science ®Google Scholar
• Truelove SC. 1988. Evolution of olsalazine. Scand J Gastroenterol. 148:3–6.
   Web of Science ®Google Scholar
• Valerino DM, Johns DG, Zaharko DS, Oliverio VT. 1972. Studies of the metabolism of methotrexate by intestinal flora-I: identification and study of biological properties of the metabolite 4-amino-4-deoxy-N10-methylpteroic acid. Biochem Pharmacol. 21:821–831.
   PubMed Web of Science ®Google Scholar
• Van Hogezand RA, Kennis HM, Van Schaik A, Koopman JP, van Hees PA, van Tongeren JH. 1992. Bacterial acetylation of 5-aminosalicylic acid in faecal suspensions cultured under aerobic and anaerobic conditions. Eur J Clin Pharmacol. 43:189–192.
   PubMed Web of Science ®Google Scholar
• Vermes A, Kuijper EJ, Guchelaar HJ, Dankert J. 2003. An in vitro study on the active conversion of flucytosine to fluorouracil by microorganisms in the human intestinal microflora. Chemotherapy. 49:17–23.
   PubMed Web of Science ®Google Scholar
• Wadworth AN, Fitton A. 1991. Olsalazine—a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in inflammatory bowel disease. Drugs. 41:647–664.
   PubMed Web of Science ®Google Scholar
• Wakabayashi C, Murakami K, Hasegawa H, Murata J, Saiki I. 1998. An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem Biophys Res Commun. 246:725–730.
   PubMed Web of Science ®Google Scholar
• Wang Y, Jiang Y, Wang BX, Qiu QY. 2002. Effects of ginsenoside Rg1 and its metabolite Rh1 on the function of immunocyte in mice. Acta Pharm Sin. 37:927–929.
   Google Scholar
• Wang Y, Liu TH, Wang W, Wang BX. 2001. Research on the transformation of ginsenoside Rg1 by intestinal flora. Zhongguo Zhong Yao Za Zhi. 26:188–190.
   PubMedGoogle Scholar
• Watanabe K, Yamashita S, Furuno K, Kawasaki H, Gomita Y. 1995. Metabolism of omeprazole by gut flora in rats. J Pharm Sci. 84:516–517.
   PubMed Web of Science ®Google Scholar
• Wienkers L C, Heath T G. 2005. Predicting in vivo drug interactions from in vitro drug discovery data. Nat Rev Drug Discov. 4:825–833.
   PubMed Web of Science ®Google Scholar
• Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE. 2004. Drug-drug interactions for udp-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (Auci/Auc) ratios. Drug Metab Dispos. 32:1201–1208.
   PubMed Web of Science ®Google Scholar
• Wilson ID, Nicholson JK. 2017. Gut microbiome interactions with drug metabolism, efficacy, and toxicity. Trans Res. 179:204–222.
   Web of Science ®Google Scholar
• Yang W, Zhang F, Wu W, Deng Z, Ma Q, Yu X, Zhao L, Kang S. 2010. Changes of intestina lflora microecology in model rats of radical plateau. Chin J Gastroenterol Hepatol. 19:543–545.
   Google Scholar
• Yang XW, Zhao J, Cui JR, Guo W. 2004. Studies on the biotransformation of escin Ia by human intestinal bacteria and the anti-tumor activities of desacylescin I. Beijing Da Xue Xue Bao. 36:31–35.
   PubMedGoogle Scholar
• Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, et al. 2012. Human gut microbiome viewed across age and geography. Nature. 486:222–227.
   PubMed Web of Science ®Google Scholar
• Zaharko DS, Bruckner H, Oliverio VT. 1969. Antibiotics alter methotrexate metabolism and excretion. Science. 166:887–888.
   PubMed Web of Science ®Google Scholar
• Zhang J, Chen Y, Sun Y, Wang R, Zhang J, Jia Z. 2018. Plateau hypoxia attenuates the metabolic activity of intestinal flora to enhance the bioavailability of nifedipine. Drug Deliv. 25:1175–1181.
   PubMed Web of Science ®Google Scholar
• Zhang M, Peng CS, Li XB. 2015. In vivo and in vitro metabolites from the main diester and monoester diterpenoid alkaloids in a traditional Chinese herb, the aconitum species. Evid Based Complement Alternat Med. 2015:252434.
   PubMed Web of Science ®Google Scholar
• Zhu JX, Wang Y, Kong LD, Yang C, Zhang X. 2004. 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. 93:133–140.
   PubMed Web of Science ®Google Scholar
• Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. 2019. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science. 363:eaat9931.
   PubMed Web of Science ®Google Scholar
• Zu XP. 2016. Interaction of effective ingredients from traditional Chinese medicines with intestinal microbiota. Chin J Chin Meter Med. 41:1766–1772.
   Google Scholar