Chronic Diarrhea: Causes and Which Tests to Do Step by Step

Chronic diarrhea is usually defined as loose or watery stools lasting longer than four weeks. The word 'diarrhea' itself is used in different ways: for one person it means frequent bowel movements, for another loose consistency (type 6-7 on the Bristol scale), for yet another an urgent need to go. For diagnosis all of these matter, as do stool volume, the presence of mucus, blood or fat (fatty stools that are hard to flush), the time of day (nocturnal diarrhea is an alarm feature) and any accompanying pain.

A practical review from American Family Physician (Burgers et al., 2020) proposes dividing it into three types that help choose tests: watery diarrhea (secretory, osmotic or functional), fatty diarrhea (from impaired digestion or absorption) and inflammatory diarrhea. Secretory watery diarrhea can result from, among other things, bile acid malabsorption, microscopic colitis, endocrine disorders and some postsurgical states; osmotic diarrhea from carbohydrate malabsorption syndromes and laxative abuse; fatty diarrhea from celiac disease, giardiasis and exocrine pancreatic insufficiency; and inflammatory diarrhea from inflammatory bowel diseases, Clostridioides difficile infection and colorectal cancer. Some diseases cause more than one type of diarrhea.

The JAMA review adds a valuable hint about the location of the source. Chronic diarrhea from the small intestine (celiac disease, SIBO) is usually associated with large-volume stools, weight loss and sometimes fatty stools, whereas diarrhea from the colon (bile acids, microscopic colitis) is associated with frequent, small stools, urgency and excess mucus. This is not a rule without exceptions, but it helps narrow the causes from a well-taken history alone.

A key observation follows from this description: irritable bowel syndrome and functional diarrhea are diagnoses of exclusion. The question remains how often other, treatable diseases hide under their label. The answer comes from the meta-analysis by Poon et al. (2022), covering patients meeting IBS criteria in secondary care. The pooled frequency of bile acid diarrhea there was 41% (7 studies, 597 people), of microscopic colitis 3% (17 studies, 5,068 people), of exocrine pancreatic insufficiency 4.6% (2 studies, 478 people), and of SIBO and lactose or fructose malabsorption on breath testing from about 19% to over 50%, depending on the test. The authors sum up that a significant proportion of patients diagnosed with IBS have an organic condition that may explain the symptoms, and failing to exclude them denies patients effective treatment. It must be remembered, though, that these are data from secondary centres and that breath tests have limited specificity, as we write in the article on breath tests.

Bile acids are secreted with bile into the small intestine and are mostly reabsorbed in the terminal ileum. When absorption is impaired (after resection or disease of the ileum or, more often, in the so-called idiopathic form), excess bile acids reach the colon, stimulate the secretion of water and electrolytes and bowel movements, and cause watery diarrhea, often with urgency. The mechanism of the idiopathic form includes reduced synthesis of FGF-19 in the ileum, which inhibits hepatic bile acid production, or genetic variants of proteins involved in this feedback (Camilleri and Nurko, 2022).

The scale of the problem is large. In a meta-analysis of six studies covering 908 people with IBS-D (Slattery et al., 2015), the frequency of bile acid malabsorption, defined as SeHCAT retention below 10% at 7 days, ranged from 16.9% to 35.3%, and pooled 28.1% (95% CI 22.6-34.0%). Camilleri and Nurko write of about 20% of adolescents and 30% of adults with chronic non-bloody diarrhea, often attributed to IBS. It is therefore worth thinking of especially with watery diarrhea with urgency, after cholecystectomy or bowel surgery, and also when standard IBS treatment does not help.

The gold standard for diagnosis is the SeHCAT test with a radiolabelled bile acid analogue, but it is expensive, involves radiation exposure and has limited availability. Alternatives are blood levels of 7α-hydroxy-4-cholesten-3-one (C4) and FGF-19, and measurement of bile acids in stool (Hughes et al., 2021; Camilleri and Nurko, 2022). In clinical practice a therapeutic trial of bile acid sequestrants is also often used. Its effectiveness is supported by studies: in the randomized, double-blind SINBAD trial (Borup et al., 2023), 168 patients received colesevelam or placebo for 12 days; remission was reached by 64% of those on colesevelam vs 16% on placebo among people diagnosed by C4 (adjusted OR 9.1) and by 59% vs 13% when diagnosed by SeHCAT (OR 11.1). A meta-analysis of six trials (182 participants; Dilmaghani et al., 2025) showed significant improvement in stool consistency and frequency (RR 1.50 and 2.80 respectively), with good tolerability and moderate certainty of evidence.

Microscopic colitis is a chronic inflammatory disease of the colon that causes chronic watery diarrhea, sometimes with abdominal pain, nocturnal diarrhea, urgency and fecal incontinence. Its diagnosis rests on histological examination of multiple biopsies from the colonic mucosa, which on endoscopy often looks normal or nearly normal. Two main histological forms are distinguished: collagenous and lymphocytic colitis (Miehlke et al., 2019). According to the JAMA review, microscopic colitis affects 13% of patients with chronic diarrhea in whom random biopsies were taken, although in a meta-analysis of people meeting IBS criteria its frequency was estimated at 3%.

Treatment is effective. In a meta-analysis of nine randomized trials (Sebastian et al., 2019), budesonide increased the chance of clinical response both at induction (OR 7.34; 95% CI 4.08-13.19) and in maintenance treatment (OR 8.35), as well as histological response, but relapses after stopping the drug were frequent (over 50%). This explains why one must not assume a 'clean' colonoscopy closes the matter: with unexplained chronic watery diarrhea the doctor should order random biopsies rather than stopping at a report of 'no abnormalities'.

Step one is history and examination: duration, character of stools (watery, fatty, with mucus or blood), time of day, accompanying pain, weight loss, medicines and supplements, recent travel and antibiotics, operations (cholecystectomy, bowel resections), chronic diseases, family history of celiac disease, inflammatory bowel disease or colorectal cancer. Common drug-related causes include certain medicines and supplements (magnesium preparations, metformin, sweeteners such as sorbitol), so reviewing the medication list is often the cheapest 'test'.

Step two is basic tests. According to the AFP review (Burgers et al., 2020), a complete blood count, CRP, anti-tTG IgA antibodies with total IgA and a basic metabolic panel are useful; they allow detection of celiac disease or inflammatory bowel disease and assessment of hydration, electrolytes and anemia. The JAMA review additionally recommends fecal calprotectin. We describe the interpretation of blood count and CRP in the knowledge base, and of calprotectin in a separate text. Deficiencies of iron, ferritin or vitamin B12 may point to malabsorption.

Step three is tests directed at the type of diarrhea. With fatty diarrhea, exocrine pancreatic function is checked (according to the 2023 AGA update, fecal elastase is the most appropriate initial test, but it must be measured in a semi-solid or solid stool, because watery stool can lower the result, and a value below 100 µg/g provides good evidence of pancreatic insufficiency) and giardiasis is excluded; with watery diarrhea, bile acid malabsorption (SeHCAT, C4, fecal bile acids or a therapeutic trial), carbohydrate intolerances (lactose, fructose) and, in selected patients, SIBO are considered; with inflammatory diarrhea, calprotectin and tests for infections, including Clostridioides difficile after antibiotics. If hyperthyroidism or other hormonal disease is suspected, TSH and other tests are added.

Step four is endoscopy. Colonoscopy with random biopsies is indicated with alarm features, with raised calprotectin or when no cause has been found despite well-chosen tests, and gastroscopy with duodenal biopsies when celiac disease or malabsorption is suspected. The British Society of Gastroenterology guidelines of 2018 (Arasaradnam et al.) and the American AGA guideline on laboratory evaluation of functional diarrhea and IBS-D (Smalley et al., 2019) organise this algorithm and are worth consulting.

On the other hand, not every chronic diarrhea requires the full set of tests. In a younger person with a typical picture and no alarm features, a few simple tests (celiac disease, calprotectin, blood count, CRP) may be enough, and further investigation is a matter of response to treatment and the doctor's decision.

Diarrhea lasting longer than 4 weeks always deserves a medical consultation. It needs urgent assessment when accompanied by: blood in the stool or black stools, unintentional weight loss, nocturnal diarrhea that wakes you from sleep, fatty or floating stools, anemia or iron deficiency, fever, dehydration (dizziness, scanty urine), severe abdominal pain, age 45 or older with new symptoms, or a family history of colorectal cancer, inflammatory bowel disease or celiac disease. In such cases colonoscopy is the standard, often together with gastroscopy.

Chronic diarrhea is rarely life-threatening, but it often goes untreated because it is filed under 'irritable bowel'. The data show that a few simple tests at the start and a careful pass through the treatable possible causes (celiac disease, bile acids, microscopic colitis, pancreatic insufficiency) give a real chance of improved quality of life. At the same time the work-up should be proportionate: in a person without alarm features there is no need to do everything at once, only in a logical order.