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Table 1 Direct impact of the gut microbiome on drug outcomes

From: Mirror, mirror on the wall: which microbiomes will help heal them all?

Effect Example Microbial mechanism
Increased efficacy Simvastatin [18] Unknown.
Decreased efficacy L-dopa [32, 33] Exact mechanism is unknown, but it is suspected that Helicobacter pylori prevents duodenal absorption of L-dopa, directly metabolizes it, or binds it and prevents absorption.
Altered target specificity Sulfasalazine [57] Many gut bacteria possess azoreductases that cleave sulfasalazine into sulfapyridine and 5-ASA. The parent drug and its metabolites have different mechanisms of action and presumably different targets.
Increased clearance Digoxin [24] Proteins encoded by the cgr operon of Eggerthella lenta metabolize digoxin to an inactivate metabolite that is more readily excreted.
Decreased clearance Pentobarbital [31] Unknown gut microbes influence the abundance of liver enzymes that metabolize pentobarbital.
Increased toxicity Irinotecan [27] For irinotecan, multiple gut bacteria prevent clearance of SN-38 (the active metabolite of irinotecan) by removing a glucuronide group. This causes SN-38 to persist in the gastrointestinal tract and results in severe diarrhea.
Indirect interference with host metabolism Acetaminophen [58] For acetaminophen, multiple gut bacteria produce p-cresol, which competes with acetaminophen for drug clearance by liver enzymes.