Medications that change the gut

Healthy state

Almost every medication you swallow meets microbes on its way. In the mouth and stomach its surroundings change, in the small intestine the active ingredient is mostly absorbed, and what is left reaches the large intestine, where by far most bacteria live. Even medications that are injected or absorbed and cleared by the liver return to the gut via the bile.

Gut bacteria are not bystanders here but a kind of second liver. They have enzymes humans lack and can split, rebuild or inactivate active ingredients. Well-known examples are heart medicines and drugs for Parkinson’s disease, which certain bacteria partly break down before they can work. Another route: the liver attaches many active ingredients to sugar units so they can leave through the bile. Some gut bacteria cut these units off again with an enzyme (β-glucuronidase), the active ingredient is absorbed a second time and acts for longer or causes side effects, such as diarrhoea with one cancer drug. This is one reason why the same medication works differently in two people.

The gut itself also decides how much of an active ingredient arrives. Stomach acid dissolves some tablets in the first place, gut movement determines how long a drug stays at the lining, and bile acids Bile acids Substances made by the liver that make fat digestible. About 95 percent are reabsorbed in the last part of the small intestine; gut bacteria transform the rest. More in the chapter “Bile acids: when bile causes diarrhoea” help fat-soluble ingredients get absorbed. Because gut flora Microbiome, gut microbiota The community of all microbes in the gut, mainly bacteria, plus viruses, fungi and archaea. Most live in the colon. More in the chapter “Building microbial diversity” differs greatly from person to person, everybody reacts a little differently.

Important to keep in perspective: that a medication changes the gut flora does not automatically mean it does harm. Treating an infection, diabetes or a heart condition usually takes priority. This chapter is meant to help you spot connections when gut symptoms are new or do not improve, and to talk to your doctor about alternatives. It is not a call to leave medications out.

Disrupted state: causes and effects

A laboratory experiment showed how many medications change the gut flora: about one in four medications that actually target human cells inhibited at least one species of gut bacteria. These included drugs from all classes, notably often antipsychotics. That holds in the test tube; at the doses reached in a person’s gut it is not always so, and whether the inhibition is noticeable for the individual remains open.

In people, the picture shows up in large groups. In three cohorts from the Netherlands, acid blockers, metformin, antibiotics and laxatives were most strongly linked to changes in the gut flora. With acid blockers, more bacteria from the mouth and throat were found in the gut, because stomach acid is a weaker barrier. The chapter on acid blockers explains this in more detail. A study in healthy people also showed less diversity after only four weeks.

Metformin is a good example of a misunderstanding. People with type 2 diabetes have a different gut flora from healthy people. But a study that compared patients with and without metformin showed that a good part of these differences comes from the drug and not from the disease. Metformin increases, among others, bacteria that make short-chain fatty acids Short-chain fatty acids Acids such as acetate, propionate and butyrate that gut bacteria make from fibre. They nourish the gut wall and act throughout the body. More in the chapter “Butyrate and other short-chain fatty acids” and the Escherichia group. It is suspected that this is related to the frequent digestive side effects, but this is not proven. So when someone’s gut flora differs from others’, it is always worth looking at the medication list before blaming the disease alone.

Painkillers of the ibuprofen and diclofenac type can not only irritate the stomach but also damage the lining of the small intestine. They block the production of prostaglandins, messengers that build mucus and keep the lining well supplied with blood. The lining becomes more permeable, small ulcers form, and blood loss can lead to iron deficiency. The gut flora evidently plays a part, as a review shows. Stomach protectors do not prevent this small intestinal damage; some studies even suggest they may worsen it.

Other drugs act via gut movement. Opioids (strong painkillers, also some cough medicines) slow the muscles and the fluid secretion in the gut and often cause stubborn constipation. Medications with an anticholinergic effect, for example some for overactive bladder, allergies, depression or psychosis, also slow the gut. Iron, calcium-containing antacids and some blood pressure drugs constipate, while magnesium and metformin tend to cause diarrhoea. When stool becomes firmer or looser as a result, the gut flora changes with it, because transit time itself is a strong influence on its composition.

Laxatives also appear high up in the studies. This is probably partly because they change the time in the gut and the water content of stool, and partly because constipated people generally have a different flora. It is hard to separate cause and effect here. That is exactly the limit of almost all studies in this field: people who take a medication usually also have a disease, and both change the gut.