Bile acids: when bile causes diarrhoea

Healthy state

Every day the liver makes 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. from cholesterol, in humans mainly cholic acid and chenodeoxycholic acid. These are the primary bile acids. Before they enter the bile, the liver attaches them to the amino acids glycine or taurine. These conjugated bile acids work like washing-up liquid: they dissolve fats so that enzymes can break them down.

At the end of the small intestine, in the ileum Ileum The last section of the small intestine. It recovers bile acids, absorbs vitamin B12 and joins the colon via the ileocaecal valve. More in the chapter “Where the small intestine meets the colon: ileum, valve and caecum”, a transporter takes back about 95 per cent and sends them to the liver via the blood. This cycle runs several times a day. At the same time, the ileum uses the hormone FGF19 to tell the liver that there are enough bile acids. The liver then makes fewer.

The small remainder reaches the large intestine, where bacteria take over. Many species first remove the glycine or taurine with the enzyme bile salt hydrolase. Only a few, mainly certain oxygen-avoiding clostridia such as Clostridium scindens, then remove a hydroxyl group (7α-dehydroxylation). This produces the secondary bile acids: cholic acid becomes deoxycholic acid, and chenodeoxycholic acid becomes lithocholic acid.

That is why secondary bile acids predominate in healthy stool. This has advantages: they inhibit germs such as C. difficile Clostridioides difficile A bacterium that can spread after antibiotics and cause severe diarrhoea with its toxins. More in the chapter “After antibiotics: C. difficile and faecal transplants”, and lithocholic acid is so poorly soluble that most of it is excreted in bound form.

Bile is made in the liver and stored and thickened in the gallbladder. After a meal, especially one containing fat, the gallbladder contracts on the signal of the hormone CCK CCK (cholecystokinin) A hormone from the duodenum. It is released in response to fat and protein, makes the gallbladder contract and calls up digestive enzymes from the pancreas. More in the chapter “The digestive chain: how stomach acid, bile and pancreas set each other off” and releases bile in a burst into the duodenum. Without a gallbladder, bile flows continuously in small amounts. The body’s whole bile acid stock is small, only a few grams, but it circulates several times a day and is used again and again.

Bile acids are more than detergents, they are also messengers. Through receptors such as FXR in the ileum and TGR5 in the gut and other tissues, they signal how much fat has arrived and, among other things, stimulate release of the satiety hormone GLP-1 GLP-1 A hormone from the gut wall that controls insulin release after eating, slows the stomach and makes you feel full. Weight-loss injections mimic it. More in the chapter “GLP-1 from the gut: what bacteria do and what “natural Ozempic” cannot do”. They also keep bacterial growth in check in the upper gut, which is why disturbed bile flow is suspected of favouring small intestinal bacterial overgrowth Small intestinal bacterial overgrowth (SIBO) Too many bacteria in the small intestine, where normally few live. Bloating and diarrhoea are typical; it is usually diagnosed with a breath test. More in the chapter “When the small intestine is too densely colonised”. This part is less well established in humans than their role in fat digestion.

Disrupted state: causes and effects

If too many bile acids reach the large intestine, they stimulate the lining to release salt and therefore water, and they speed up gut movement. At high concentrations, the bile acids with two hydroxyl groups, chenodeoxycholic acid and deoxycholic acid, have the strongest effect. In a study in humans, cholic acid, by contrast, caused no water secretion. The result is watery, often urgent diarrhoea.

Experts distinguish three types. Type 1: the ileum has been operated on or is inflamed, for example in Crohn's disease, and no longer takes the bile acids back. Type 2: there is no identifiable cause. Here the FGF19 feedback is often too weak, so the liver makes too many bile acids. Type 3: the loss occurs with other conditions, for example after gallbladder removal, with coeliac disease Coeliac disease An autoimmune disease in which gluten damages the lining of the small intestine. It is diagnosed with a blood test and usually a biopsy while you are still eating gluten. More in the chapter “Lactose, fructose, gluten: making sense of intolerances”, small intestinal bacterial overgrowth or after radiotherapy.

According to reviews, bile acid loss is behind the symptoms in about a quarter to a third of people diagnosed with diarrhoea-predominant IBS Irritable bowel syndrome Recurring abdominal pain linked to bowel movements, without tests finding another cause. Today it is understood as a disorder of gut–brain interaction. More in the chapter “The gut-brain axis”, and severe loss in about one in ten.

The gut microbiota 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” also plays a role. In diarrhoea-predominant IBS, the stool contains more primary and fewer secondary bile acids, together with fewer bacteria from the Ruminococcaceae family, which can convert bile acids. The higher the share of primary bile acids, the softer and more frequent the stool. Whether the changed microbiota is a cause or a consequence of fast gut transit is still open.

Antibiotics can shift this balance strongly because they hit precisely the oxygen-avoiding converters. In one study, after vancomycin the stool contained almost only conjugated primary bile acids, and the secondary ones had dropped sharply. This favours C. difficile. Whether antibiotics also cause persistent bile acid diarrhoea in humans this way has barely been studied.

Important: “secondary” does not automatically mean harmless. At high levels, deoxycholic acid itself causes the strongest diarrhoea and, with a permanently very high-fat diet, is linked to damage to the gut lining and to colorectal cancer. What is healthy is not one particular type, but the balance between amount, reabsorption and conversion.

Diet also shifts the bile acid environment. In a small study of nine volunteers, even five days of an entirely animal-based, high-fat, high-protein diet changed the gut microbiota: bacteria that tolerate high bile concentrations (including Bilophila wadsworthia) increased, fibre-using species decreased. Fatty meals also send more bile into the gut. This does not mean fat itself is harmful. It shows that the amount and type of fat and fibre help decide how much bile acid and which type of converter reaches the large intestine.

Bile acid diarrhoea is often overlooked because it resembles IBS with diarrhoea: watery, often urgent stools, sometimes at night, often after fatty meals, plus bloating. Clues can be an earlier operation on the ileum or gallbladder, Crohn’s disease, coeliac disease, or diarrhoea that does not respond to the usual IBS treatments. Guidelines on chronic diarrhoea include checking for bile acid diarrhoea as standard, but access to the tests varies by country. A single bout of diarrhoea after a feast, by contrast, is normal and no cause for concern.