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 | 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. |