Gut Microbiota-Mediated Drug-Antibiotic Interactions

Abstract

Xenobiotic metabolism involves the biochemical modification of drugs and phytochemicals in living organisms, including humans and other animals. In the intestine, the gut microbiota catalyzes the conversion of hydrophilic drugs into absorbable, hydrophobic compounds through hydroxyzation and reduction. Drugs and phytochemicals are transformed into bioactive (sulfasalazine, lovastatin, and ginsenoside Rb1), bioinactive (chloramphenicol, ranitidine, and metronidazole), and toxic metabolites (nitrazepam), thus affecting the pharmacokinetics of the original compounds.Antibiotics suppress the activities of drug-metabolizing enzymes by inhibiting the proliferation of gut microbiota. Antibiotic treatment might influence xenobiotic metabolisms more extensively and potently than previously recognized and reduce gut microbiotamediated transformation of orally administered drugs, thereby altering the systemic concentrations of intact drugs, their metabolites, or both. This review describes the effects of antibiotics on the metabolism of drugs and phytochemicals by the gut microbiota.

Regulation of Hepatic Drug-Metabolizing Enzymes in Germ-Free Mice by Conventionalization and Probiotics

“…Intestinal microbiota modifiers, such as probiotics, antibiotics, and conventionalization to the environment, may both positively and negatively impact human health (Boyle et al, 2006;Carvalho et al, 2012;Kim, 2015;Vandenplas et al, 2015). Although the excessive use of antibiotics has raised concerns regarding their potential adverse health effects, leading to more stringent usage in medical practice, less is known regarding the safety of probiotics.…”

Drug Metabolism by the Host and Gut Microbiota: A Partnership or Rivalry?

“…A recent analysis investigating the impact of a variety of drugs, including antiobiotics, digoxin, phenacetin, and sulfasalazine, indicated that antibiotics had the greatest impact on the functional activity of the gut microbiome (Maurice et al, 2013). The extent to which antibiotic treatment modulates the metabolism of orally administered drugs is further scrutinized in this issue (Kim, 2015). In addition to drugs, a number of xenobiotics can alter the gut microbiota.…”

Anti-inflammatory effects of vina-ginsenoside R2 and majonoside R2 isolated from Panax vietnamensis and their metabolites in lipopolysaccharide-stimulated macrophages

“…Therefore, their hydrophilic constituents inevitably come into contact with gut microbiota in the gastrointestinal tract [8][9][10]. Gut microbiota metabolize these hydrophilic constituents to hydrophobic bioactive or non-bioactive compounds in the intestine before they get absorbed into the blood [9][10][11]. For example, orally administered ginseng (the root of Panax ginseng CA Meyer) and its constituents, ginsenosides Rb1, Rb2, and Rc, are metabolized by human gut microbiota to 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (compound K), which is absorbed into the blood [7,[12][13][14].…”

“…Therefore, their hydrophilic constituents inevitably come into contact with gut microbiota in the gastrointestinal tract [8][9][10]. Gut microbiota metabolize these hydrophilic constituents to hydrophobic bioactive or non-bioactive compounds in the intestine before they get absorbed into the blood [9][10][11].…”