TABLE 1

Effects of antibiotics on the gut microbiota-mediated metabolisms of drugs and phytochemicals

DrugReactionMetaboliteModeAntibioticsaReferences
ProntosilAzo reductionSulfanilamideBioactive−Fouts et al., 1957; Gingell et al., 1971; Gingell and Bridges, 1973
NeoprontosilAzo reductionSulfanilamideBioactive−Fouts et al., 1957; Gingell et al., 1971
SulfasalazineAzo reduction5-Aminosalicylic acidBioactive−Peppercorn and Goldman, 1976; Hayllar and Bjarnason,1991; Klotz, 1985
BalsalazideAzo reduction5-Aminosalicylic acidBioactive−Chan et al., 1983
NitazepamNitro reduction7-AminonitrazepamBioactive−Rafii et al., 1997; Takeno et al., 1993; Takeno and Sakai, 1990
ClonazepamNitro reduction7-AminoclonazepamToxic−Elmer and Remmel, 1984
MisonidazoleNitro reduction1-(2-Aminoimidazol-1-yl)-3-methoxypropan-2-olToxic−Koch et al., 1980; Sheldon et al., 1984
SulfinpyrazoneSulfoxide reductionSulfinpyrazone sulfideBioinactive+Strong et al., 1987
SulindacSulfoxide reductionSulindac sulfideBioinactive+Strong et al., 1987
RanitidineN-oxide reductionHydroxyiminoranitidineBioinactive+Basit et al., 2002; Machavaram et al., 2006
nizatidineN-oxide reductionHydroxyiminonizatidineBioinactive+Basit and Lacey, 2001; Basit et al., 2004; Machavaram et al., 2006
Loperamide oxideN-oxide reductionLoperamideBioinactive+Lavrijsen et al., 1995; Kamali and Huang, 1996
DigoxinC = C reduction and deglycosylationDihydroxydigoxin, dihydroxydigoxigeninBioinactive+Lindenbaum et al., 1981; Magnusson et al., 1982
ZonisamieO-N reduction/ring fission2-SulfamoyacetylphenolBioinactive+Kitamura et al., 1997
metronidazoleC-N reduction/ring fissionN-(2-hydroxyethyl)-oxamic acid, acetamideBioinactive+Koch et al., 1979; Koch and Goldman, 1979; Pierce et al., 2014
LactuloseDeglycosylationFructose, galactose, organic acidsBioactive−Elkington et al., 1969; van Berlo et al., 1988
Glucuronate-conjugated drugs: SN-38GDeglycosylationSN-38G→SN-38Bioactive/Toxic−Simon and Gorbach, 1984; Orme and Back, 1990; Adlercreutz and Martin,1980; Kehrer et al., 2001
Acetaminophen-G→ acetaminophen
Sodium picosulfateDesulfation4,4′-(Pyridin-2-ylmethanediyl)-diphenolBioactive−Kim and Kobashi, 1986; Kim et al., 1992; Kobashi et al., 1986
l-dopaDehydroxylationTyramine, m-hydroxyphenylacetic acidBioinactive+Goldin et al., 1973; Peppercorn and Goldman, 1976
FlucytosineDeamination5-fluorouracilBioactive−Vermes et al., 2003; Harris et al., 1986
LevamizoleRing fission and reductionLevametabol I, II, IIIBioinactive+Shu et al., 1991
RisperidoneRing fissionDihydroxyrisperidone, hydroxyl-keto-risperidoneBioinactive+Meuldermans et al., 1994
LovastatinHydroxylation and ring fission2-Hydroxylovastatic acidBioactive−Yoo et al., 2014;
SimvastatinHydroxylation and ring fissionSimvastatin acidBioactive−Methaneethorn et al., 2014
IsoflavonesReductionEquol, phenolic acidsBioactive/
bioinactive−Setchell and Clerici, 2009; Sepehr et al., 2009; Yokoyama and Suzuki, 2008; Kim et al., 1998b
SennosidesReduction and deglycosylationSennidinsBioactive−Hattori et al., 1982; Kobashi et al., 1980; Yang et al., 1996
GlycyrrhizinDeglycosylation18β-D-glycyrrhetinic acidBioactive−Hattori et al., 1983; Takeda et al., 1996; Kim et al., 2000
Ginsenoside Rb1Deglycosylation3β-D-glucopyranosyl-20S-protopanaxatriolBioactive−Akao et al., 1998; Xu et al., 2014; Joh et al., 2011
Puerarin/DaidzinDeglycosylation, hydroxylation, and methylationDaidzein, calycosin, equol, phenolic acidsBioactive−Setchell and Clerici, 2010; Sepehr et al., 2009; Yokoyama and Suzuki, 2008; Kim et al., 1998b; Yasuda and Ohsawa, 1998;
Hesperidin/naringin/rutin/poncirinDeglycosylationHesperetin/naringenin/Quercetin/ponciretinBioactive−Kim et al., 1998a; Jin et al., 2010
FlavonoidsRing fissionPhenolic acidsBioinactive/bioactive−Kim et al., 1998a; Selma et al., 2009; Cardona et al., 2013

  • ↵a Antiobiotics : +, synergistic ; −, antagonistic.