[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › Gut microbiome and drug response [Pharmacology](https://durgical.com/en/pharmacology/) · Topic # Gut microbiome and drug response The bacteria in the gut can switch drugs on, switch them off or make them more toxic, which helps explain why people respond differently. Updated 2026-11-01 The gut holds a huge community of microbes with their own enzymes. Oral drugs, and drugs that return to the gut in bile, meet these enzymes before or after absorption. Bacteria can activate prodrugs, inactivate drugs, undo the liver's conjugation and change host metabolism indirectly. Antibiotics, diet and disease change the microbiome, and therefore drug response. ## Key points - Activation: gut bacteria split sulfasalazine into sulfapyridine and 5-aminosalicylic acid, the part that acts on the colon. - Inactivation: some strains of Eggerthella lenta reduce digoxin to inactive products; the digoxin label notes that in about one in ten patients colonic bacteria degrade a large share of the dose. - Antibiotics can change this: the digoxin label lists clarithromycin as raising digoxin absorption in patients whose gut bacteria inactivate it. - Reactivation: bacterial enzymes can undo the liver's glucuronide conjugation, freeing active or toxic drug in the gut, as described for irinotecan and NSAIDs. - Enterohepatic recycling (conjugate in bile, freed by bacteria, reabsorbed) can prolong a drug's action. ## How microbes change drugs - Reduction (for example, of azo bonds or of the lactone ring of digoxin) - Hydrolysis and deconjugation (bacterial beta-glucuronidases) - Decarboxylation: a bacterial tyrosine decarboxylase (in Enterococcus faecalis) can turn levodopa into dopamine in the gut, before it reaches the brain (early evidence) - Indirect effects: microbial products such as bile acids act on host receptors that control drug-metabolising enzymes ## Digoxin and Eggerthella lenta Some strains of E. lenta reduce digoxin to dihydrodigoxin, which is inactive. A 2021 review in Clinical Pharmacokinetics links this to a cardiac glycoside reductase gene cluster that is switched on by digoxin in those strains only. Since not everyone carries these strains, it is a model of how both human and microbial genes shape a drug's level. ## Enterohepatic recycling and toxicity The liver attaches glucuronide to many drugs and sends them into bile. In the intestine, bacterial enzymes can remove that group, so the drug is reabsorbed (recycling) or the active form harms the gut lining. The same review describes this for the cancer drug irinotecan (its inactive glucuronide is turned back into the active metabolite SN-38 in the gut, which may add to diarrhoea) and for NSAIDs (mostly animal data), and the influence of the microbiome on immune checkpoint inhibitors. ## Why it matters in practice Starting or stopping antibiotics, a change in diet, bowel surgery or diarrhoea can change the effect of drugs that depend on gut bacteria. The field is still young: for most drugs there is no routine test, but the mechanism is a reason to look again at levels and effect after big changes in gut flora. ## Memory aid Gut bugs can turn drugs ON (sulfasalazine), OFF (digoxin) or BACK ON (glucuronide removal). ## Test yourself Think of the answer, then tap the question to see it. ## Which part of sulfasalazine is released by gut bacteria and acts on the colon? 5-aminosalicylic acid; bacteria split sulfasalazine into sulfapyridine and 5-aminosalicylic acid. ## Why can an antibiotic raise digoxin levels in some patients? In patients whose gut bacteria inactivate digoxin, an antibiotic can reduce those bacteria, so more digoxin is absorbed intact. ## What do bacterial beta-glucuronidases do to drug conjugates in the gut? They remove the glucuronide that the liver attached, freeing the drug so it can be reabsorbed or damage the intestinal lining. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/topics/gut-microbiome-and-drug-response/) ## Related classes - [Cardiac glycosides](https://durgical.com/en/pharmacology/classes/cardiac-glycosides/) - [Nonsteroidal anti-inflammatory drugs (NSAIDs)](https://durgical.com/en/pharmacology/classes/nonsteroidal-anti-inflammatory-drugs/) ## Example drugs - [Digoxin](https://durgical.com/en/pharmacology/digoxin/) - [Sulfasalazine](https://durgical.com/en/pharmacology/sulfasalazine/) - [Irinotecan](https://durgical.com/en/pharmacology/irinotecan/) - [Levodopa + carbidopa](https://durgical.com/en/pharmacology/levodopa-carbidopa/) - [Clarithromycin](https://durgical.com/en/pharmacology/clarithromycin/) [← All of pharmacology](https://durgical.com/en/pharmacology/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [Contribution of the Gut Microbiome to Drug Disposition, Pharmacokinetic and Pharmacodynamic Variability](https://pmc.ncbi.nlm.nih.gov/articles/PMC8332605/) (Clinical Pharmacokinetics (open access, PubMed Central), 2021); [DailyMed - DIGOXIN tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f3d29508-e7cc-47ff-845d-b5375ee30407) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - SULFASALAZINE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=88441a9f-b4f9-455d-a355-46fb30699a7b) (DailyMed (U.S. National Library of Medicine), 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/topics/gut-microbiome-and-drug-response/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/topics/gut-microbiome-and-drug-response/