{"product_id":"understanding-bile-acid-malabsorption-a-complete-guide-to-causes-diagnosis-and-treatment-of-bile-acid-related-chronic-diarrhea","title":"Understanding Bile Acid Malabsorption: A Complete Guide to Causes, Diagnosis, and Treatment of Bile Acid–Related Chronic Diarrhea","description":"\u003cp\u003e\u003cstrong\u003eSummary:\u003c\/strong\u003e A 2024 systematic review published in the \u003cem\u003eEuropean Journal of Internal Medicine\u003c\/em\u003e shows that bile acid malabsorption (BAM) — a failure of the gut to reabsorb bile acids properly — is a common but seriously underdiagnosed cause of chronic diarrhea. Between 1 in 4 and 1 in 3 patients with unexplained chronic diarrhea turn out to have BAM, yet up to half wait more than five years for the correct diagnosis. Accurate tests exist, including the 75SeHCAT scan, the 48-hour fecal bile acid test, and blood levels of C4 and FGF19. But these tests are not widely available. So most doctors diagnose BAM by giving a bile acid sequestrant drug and watching for improvement. Beyond sequestrants, promising new treatments include FXR agonists, FGF19 analogues, GLP-1 receptor agonists, and approaches that modify the gut microbiome.\u003c\/p\u003e\n\n\u003ch1\u003eAdvances in the pathophysiology, diagnosis and management of chronic diarrhoea from bile acid malabsorption\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eBackground: Why Bile Acid Malabsorption Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#normal\"\u003eHow Bile Acids Normally Work\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#types\"\u003eThe Four Types of Bile Acid Malabsorption\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#methods\"\u003eHow the Researchers Reviewed the Evidence\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#prevalence\"\u003eHow Common Is BAM, and Who Is at Risk?\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#diagnosis\"\u003eDiagnosing BAM: What Tests Are Available\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#treatment\"\u003eTreatment Options for BAM\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#implications\"\u003eWhat This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations of the Evidence\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003ePractical Recommendations for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eBAM is a common, treatable cause of chronic diarrhea, found in roughly 25% to 35% of patients with unexplained chronic diarrhea in a US clinic population.\u003c\/li\u003e\n\u003cli\u003eUp to half of patients with BAM report symptoms lasting more than five years before receiving the correct diagnosis.\u003c\/li\u003e\n\u003cli\u003eThe 75SeHCAT scan is the most accurate test for BAM, but it is not widely available and requires a nuclear medicine department.\u003c\/li\u003e\n\u003cli\u003eAbout two-thirds of patients with unexplained diarrhea and confirmed BAM improved on bile acid sequestrant therapy, compared with one-third without BAM.\u003c\/li\u003e\n\u003cli\u003eEmerging treatments include FXR agonists, FGF19 analogues, GLP-1 receptor agonists, and approaches that modify the gut microbiome.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eBackground: Why Bile Acid Malabsorption Matters\u003c\/h2\u003e\n\n\u003cp\u003eBile acid malabsorption (BAM) means the gut does not reabsorb bile acids the way it should. Bile acids are detergent-like molecules the liver makes to digest fat. When too many of them reach the lower intestine, they trigger chronic diarrhea — a condition doctors sometimes call cholorrhea (bile-acid diarrhea).\u003c\/p\u003e\n\n\u003cp\u003eThis is not a minor nuisance condition. The symptoms can include an urgent need to pass stool, fecal incontinence (loss of bowel control), fatigue, dizziness, and a feeling of faintness. Together, these problems can lead to depression and a significantly reduced quality of life.\u003c\/p\u003e\n\n\u003cp\u003eThe review's authors make a blunt point: BAM is treatable, but it is missed far too often. A diagnostic delay is common, and up to one-half of patients with BAM report symptoms lasting more than five years before they receive the correct diagnosis. Timely and accurate identification of BAM is therefore \"a major unmet need\" in digestive medicine.\u003c\/p\u003e\n\n\u003ch2 id=\"normal\"\u003eHow Bile Acids Normally Work\u003c\/h2\u003e\n\n\u003cp\u003eTo understand what goes wrong in BAM, it helps to understand the normal bile acid cycle, known as the enterohepatic circulation (the loop between the liver and the intestine).\u003c\/p\u003e\n\n\u003ch3\u003eMaking and releasing bile acids\u003c\/h3\u003e\n\u003cul\u003e\n  \u003cli\u003eThe liver builds bile acids from cholesterol. The \"classical pathway\" uses the enzymes cholesterol 7α-hydroxylase (CYP7A1) and CYP8B1; the \"alternative pathway\" uses CYP27A1.\u003c\/li\u003e\n  \u003cli\u003eThe two primary bile acids are \u003cstrong\u003echolic acid (CA)\u003c\/strong\u003e and \u003cstrong\u003echenodeoxycholic acid (CDCA)\u003c\/strong\u003e.\u003c\/li\u003e\n  \u003cli\u003eThe liver attaches (conjugates) these acids to taurine or glycine using two enzymes: bile acid CoA synthase (BACS) and BA-CoA-amino acid N-acetyltransferase (BAAT).\u003c\/li\u003e\n  \u003cli\u003eThe finished bile acids are pumped into bile by the bile salt export pump (BSEP). A separate transporter, MRP2, handles other substances such as bilirubin and glutathione.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe gallbladder stores and concentrates bile between meals. During fasting, roughly 20% of gallbladder contents empty at the end of phase II of the migrating myoelectric complex. The migrating myoelectric complex is a periodic wave of gut muscle activity. This emptying is under the control of the vagus nerve and the hormone motilin. After a meal, more than 50% empties because fat triggers release of the hormone cholecystokinin (CCK).\u003c\/p\u003e\n\n\u003cp\u003eIn healthy people, fasting blood levels of bile acids run about 0.2 to 0.7 µM (micromoles per liter). After each meal they rise to about 4 to 5 µM. This rhythm is tightly controlled.\u003c\/p\u003e\n\n\u003ch3\u003eThe feedback loop between gut and liver\u003c\/h3\u003e\n\n\u003cp\u003eWhen bile acids reach the terminal ileum (the last part of the small intestine), they switch on a receptor called the \u003cstrong\u003efarnesoid X receptor (FXR)\u003c\/strong\u003e. Working with a partner receptor called RXR, FXR increases production of a hormone-like protein called \u003cstrong\u003efibroblast growth factor 19 (FGF19)\u003c\/strong\u003e. In mice the equivalent protein is FGF15.\u003c\/p\u003e\n\n\u003cp\u003eFGF19 then travels through the bloodstream to the liver and gallbladder. In the gallbladder it binds to the FGFR4\/β-Klotho receptor and inhibits gallbladder contraction. In the liver, the same receptor activates JNK\/ERK signalling, which shuts down CYP7A1 and CYP8B1 and therefore reduces bile acid production. A second braking pathway, FXR–SHP, works alongside it.\u003c\/p\u003e\n\n\u003cp\u003eBile acids also act through a different receptor, \u003cstrong\u003eGPBAR-1\u003c\/strong\u003e (G-protein bile acid receptor 1). In the intestine this triggers release of peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2). These hormones influence glucose and insulin metabolism and appetite, and they act on GPBAR-1 receptors in brown fat (heat-generating fat tissue) and muscle. In gallbladder muscle, GPBAR-1 signalling raises cAMP and PKA, opens ATP-regulated potassium channels, and relaxes the muscle so the gallbladder can refill.\u003c\/p\u003e\n\n\u003ch3\u003eRecycling — and what happens when recycling fails\u003c\/h3\u003e\n\n\u003cp\u003eThe terminal ileum reabsorbs more than 95% of bile acids — roughly 19 out of every 20 molecules. Only about 5% are lost in stool each day (about 1 in 20). Reabsorbed bile acids travel back to the liver through the portal vein, completing a circuit that runs 4 to 12 times daily. About 10 to 50% of the reabsorbed bile acids spill over into the general circulation rather than staying in the loop.\u003c\/p\u003e\n\n\u003cp\u003eWhatever reaches the colon meets gut bacteria, which convert primary bile acids into secondary bile acids. Some of these are reabsorbed by passive diffusion. The kidney also contributes: it takes up bile acids through the apical sodium-dependent bile acid transporter (ASBT) in the proximal tubule, and filtration is regulated by MRP2, 3 and 4 transporters.\u003c\/p\u003e\n\n\u003cp\u003eWhen this system breaks down, too many bile acids collect in the lower gastrointestinal tract. The consequences are a chain reaction:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003eAbnormal transport of water and sodium in the bowel\u003c\/li\u003e\n  \u003cli\u003eDamage to the mucosal lining (the surface layer of the gut)\u003c\/li\u003e\n  \u003cli\u003eIncreased mucus secretion\u003c\/li\u003e\n  \u003cli\u003eFaster intestinal motility (quicker transit of stool)\u003c\/li\u003e\n  \u003cli\u003eGut dysbiosis (an imbalanced gut bacterial community)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"types\"\u003eThe Four Types of Bile Acid Malabsorption\u003c\/h2\u003e\n\n\u003cp\u003eDoctors divide BAM into four types based on what is causing it. Knowing the type guides treatment.\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eType 1 — ileal disease.\u003c\/strong\u003e Defective bile acid reabsorption because the terminal ileum is damaged or removed. This is frequently seen in Crohn's disease, both with and without surgical removal of the ileum, where reported rates range from 11% to 76%, and higher still in some reports. It also occurs after ileal resection for any reason and after radiation enteropathy (bowel injury from radiation therapy). It can show up as osmotic diarrhea (caused by substances pulling water into the bowel) or as true steatorrhea (fatty stool from fat malabsorption).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eType 2 — idiopathic (primary) BAM.\u003c\/strong\u003e Here no structural defect in absorption can be documented. It may appear as primary bile acid diarrhea or as the diarrhea-predominant form of irritable bowel syndrome (IBS-D). It is associated with reduced bacterial conversion of primary bile acids into secondary bile acids.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eType 3 — non-ileal conditions causing BAM.\u003c\/strong\u003e Other diseases or surgeries disrupt bile acid handling without direct ileal damage. Examples include post-cholecystectomy diarrhea, which occurs after gallbladder removal. Examples include post-vagotomy diarrhea, which occurs after vagus nerve surgery. Examples include chronic pancreatitis with impaired bicarbonate secretion. Examples include celiac disease with villous atrophy, which is flattening of the intestinal absorptive surface. Examples include impaired gallbladder and small bowel motility. In some cases, prevalence is comparable to healthy people.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eType 4 — excessive bile acid synthesis without primary malabsorption.\u003c\/strong\u003e The liver simply makes too many bile acids. This occurs mainly in hypertriglyceridemia (high blood triglycerides) and during diabetes treatment with metformin. It is also seen in metabolic dysfunction-associated steatotic liver disease (MASLD, formerly called fatty liver disease) and in people with obesity.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eGenetic contributors to Type 2 BAM\u003c\/h3\u003e\n\n\u003cp\u003eGenetics matter, but only rarely cause the problem on their own. Identified genetic variants explain roughly 1% of primary BAM cases. Key findings include:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003eThe rs3808607 T\u0026gt;G polymorphism in the promoter region of CYP7A1 is associated with a higher ratio of 7α-hydroxy-4-cholesten-3-one (C4) to cholesterol in patients who develop bile acid diarrhea after ileal resection surgery. People carrying the TT (AA) genotype appear to have about a twofold increase in bile acid synthesis.\u003c\/li\u003e\n  \u003cli\u003eHeterozygotes for the rs8192877 A\u0026gt;G variant (people carrying one copy) show about double the fecal primary bile acids compared with AA homozygotes, and GG homozygotes show even higher levels. This variant also relates to colorectal adenoma (polyp) risk.\u003c\/li\u003e\n  \u003cli\u003eOther variants may alter the ASBT transporter, reduce FGF19 production, or blunt the liver's ability to shut down bile acid synthesis.\u003c\/li\u003e\n  \u003cli\u003eMutations affecting the FGF19\/FGFR4-β-Klotho\/ERK1\/2\/CYP7A1 axis can disrupt the feedback brake. Notably, impaired release of ileal FGF19 occurs in IBS-D patients who respond to cholestyramine, suggesting that excess liver bile acid production can indeed result from broken FGF19 signalling.\u003c\/li\u003e\n  \u003cli\u003eThe GPBAR-1 SNP rs11554825 has a minor allele frequency of 41%. This SNP was correlated with symptoms in a study. The study compared scintigraphically assessed small bowel and colonic transit in 230 healthy controls and 414 patients with functional gastrointestinal disorders. Of those patients, 84 had alternating IBS, 157 had constipation-predominant IBS, and 173 had diarrhea-predominant IBS.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe authors note that the role of gut microbiota in type 2 BAM still requires further study.\u003c\/p\u003e\n\n\u003ch3\u003eType 3 in focus: after gallbladder removal\u003c\/h3\u003e\n\n\u003cp\u003eCholecystectomy (gallbladder removal) is a common trigger. Without a gallbladder, bile drips more continuously and is less concentrated. People who have had their gallbladder removed show about double the recycling of the bile acid pool through the intestine. This accelerated recycling is tied to a twofold increase in liver bile acid synthesis and higher bile acid and cholesterol secretion into bile.\u003c\/p\u003e\n\n\u003cp\u003eEven so, the bile acid pool stays constant and fat is digested and absorbed normally. The problem is exposure: gut bacteria now meet more primary bile acids, converting them into secondary bile acids — mainly deoxycholic acid (DCA). The pool becomes enriched in more hydrophobic (water-repelling), less hydrophilic bile acids, which can disrupt cell membranes and cause cell lysis (cell breakdown). After surgery, cholic acid synthesis dips slightly, but the pathway CA → 7α-dehydroxylation → DCA increases, delivering more DCA back to the liver and suppressing cholic acid production. This profile does not change in the long term.\u003c\/p\u003e\n\n\u003cp\u003eThe reported incidence of diarrhea after cholecystectomy varies widely — from 2% to 50% — depending on the population studied, the study design, and how diarrhea was defined. It usually resolves or improves over weeks to months — about 1 in 50 to 1 in 2 patients depending on the group studied. Some authors report BAM in 68% to 86% of cholecystectomy patients. But a larger analysis of 25 studies found that only 9.1% of patients with diarrhea after cholecystectomy had BAM. Two-thirds of those patients were diagnosed with BAM.\u003c\/p\u003e\n\n\u003ch3\u003eType 3 in focus: microscopic colitis and other causes\u003c\/h3\u003e\n\n\u003cp\u003eIn microscopic colitis, BAM results from villous atrophy, inflammation, and collagen deposition in the ileum. A 75SeHCAT retention below 10% was found in about 44% of patients with collagenous colitis and chronic diarrhea — nearly 1 in 2. Almost 80% of those patients responded to bile acid sequestrant therapy, which suggests treating all patients with microscopic colitis even if their 75SeHCAT test is negative.\u003c\/p\u003e\n\n\u003cp\u003eType 4 causes deserve attention too. About 20% of patients taking metformin (1 in 5) had accelerated bowel transit times. Patients with obesity and hypertriglyceridemia can also show increased bile acid synthesis and idiopathic BAM.\u003c\/p\u003e\n\n\u003ch2 id=\"methods\"\u003eHow the Researchers Reviewed the Evidence\u003c\/h2\u003e\n\n\u003cp\u003eThe authors ran a systematic literature search in PubMed for studies on BAM published from 1965 to May 19, 2024. The search combined keywords and medical subject headings (MeSH) related to BAM:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\"bile acid malabsorption,\" \"bile acid diarrhoea,\" \"bile salt malabsorption,\" \"bile salt diarrhoea,\" or \"BAM\"\u003c\/li\u003e\n  \u003cli\u003eCombined with \"diarrhoea,\" \"chronic diarrhoea,\" or \"malabsorptive diarrhoea\"\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eStudies were included if they (1) focused on BAM and its association with bile-acid-induced diarrhea, and (2) provided original data. Reviews, editorials, and letters were excluded unless they contained relevant data. The researchers also checked the reference lists of selected articles to find cited studies that might have been missed in the initial search.\u003c\/p\u003e\n\n\u003ch2 id=\"prevalence\"\u003eHow Common Is BAM, and Who Is at Risk?\u003c\/h2\u003e\n\n\u003cp\u003eBAM is common in people with unexplained chronic diarrhea — and the numbers vary widely depending on who is tested and how.\u003c\/p\u003e\n\n\u003cp\u003eIn a US population study of patients referred to a gastroenterology outpatient clinic, the prevalence of chronic diarrhea was about 1%. Among those with unexplained chronic diarrhea, BAM was found in roughly 25% to 35% — between 1 in 4 and 1 in 3 patients. About 30% of patients treated for diarrhea-predominant irritable bowel syndrome (IBS-D) — nearly 1 in 3 — have idiopathic BAM.\u003c\/p\u003e\n\n\u003cp\u003eRisk is higher in specific groups. These groups include people who have had ileal resection. They include people with terminal ileal disease, such as Crohn's disease or radiation-induced injury. They include people with diseases affecting gut motility or absorption, such as celiac disease. They include people whose bile acid delivery to the small intestine is disturbed, most notably after cholecystectomy. BAM may also contribute to post-vagotomy diarrhea, since these patients show higher fecal bile acid excretion.\u003c\/p\u003e\n\n\u003cp\u003eA Danish study conducted between 2003 and 2021 identified 5,264 people with BAM based on the 75SeHCAT test. The BAM group was compared with age- and sex-matched controls from the general population. Those in the BAM group had more other medical conditions. They used more healthcare services. They had lower levels of education and income.\u003c\/p\u003e\n\n\u003ch3\u003ePrevalence by type\u003c\/h3\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eType 1:\u003c\/strong\u003e In patients with chronic watery diarrhea, 75SeHCAT testing found BAM in 34% (about 1 in 3).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eType 2:\u003c\/strong\u003e Prevalence is estimated in only a few studies and appears as low as 1% of new cases of chronic diarrhea and 3% of all chronic diarrhea cases — suggesting widespread underdiagnosis. Yet 51% of patients with unexplained diarrhea who underwent 48-hour fecal bile acid testing had BAM. About two-thirds of them improved with bile acid sequestrant therapy, compared with only one-third when BAM was absent. In patients with chronic diarrhea tested by 75SeHCAT, BAM was detected in 38% of cases, with type 2 accounting for 28%. Other reports found BAM by 75SeHCAT in 50% of patients, with one-third having IBS-D.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eType 3:\u003c\/strong\u003e In patients with chronic watery diarrhea, 75SeHCAT found BAM in 28%.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eA systematic review estimated the population prevalence of BAM at more than 1% and reported that about 30% of patients with chronic diarrhea had been tested by 75SeHCAT. In 15 prospective studies of patients with IBS-D-like symptoms, the prevalence of BAM by 75SeHCAT was 10% overall — moderate BAM in 32% and mild BAM in 26% of those tested. Response rates to cholestyramine (a bile acid sequestrant) were 96% in severe BAM and 70% in mild BAM.\u003c\/p\u003e\n\n\u003cp\u003eAbout one-fourth of IBS-D or functional diarrhea patients test positive for bile acid diarrhea. BAM is also linked to post-infectious diarrhea. Of patients with a history of acute gastroenteritis, 55% had a positive 75SeHCAT test. Of patients with post-infectious diarrhea, 18% had BAM that responded to cholestyramine.\u003c\/p\u003e\n\n\u003cp\u003eBile acid levels differ across IBS subtypes. Patients with IBS-D who secrete more bile acids showed high fecal levels of primary unconjugated bile acids. These patients also showed high serum C4, especially at higher body size. Levels were lower in IBS with constipation (IBS-C) and in healthy volunteers. This supports a role for bile acids in IBS itself and points to serum C4 and fecal primary and secondary unconjugated bile acids as potential biomarkers.\u003c\/p\u003e\n\n\u003ch2 id=\"diagnosis\"\u003eDiagnosing BAM: What Tests Are Available\u003c\/h2\u003e\n\n\u003cp\u003eBAM is frequently underdiagnosed, and early diagnosis matters because it prevents unnecessary tests and improves quality of life. Every available test has limitations, but each can identify patients who will benefit most from treatment. Because of limited availability and cost, these tests are rarely used in combination.\u003c\/p\u003e\n\n\u003ch3\u003e1. Empiric trial of bile acid sequestrants\u003c\/h3\u003e\n\n\u003cp\u003eThis is the practical first step. Empiric diagnosis of BAM is based mainly on the clinical response to bile acid sequestrants. This approach is recommended in patients with unexplained chronic diarrhea when specific tests are not available. No studies have compared the accuracy of empiric treatment against specific testing.\u003c\/p\u003e\n\n\u003cp\u003eThe most important limitation is poor patient compliance — patients may not tolerate the medication. False-negative results can occur partly because bile acid sequestrants taste unpleasant.\u003c\/p\u003e\n\n\u003ch3\u003e2. The 75SeHCAT test\u003c\/h3\u003e\n\n\u003cp\u003eThis is the most accurate test for identifying both the presence and the severity of BAM. It works by measuring how much bile acid remains in the abdomen seven days after the patient swallows it. The test uses a synthetic conjugated bile acid (homotaurocholic acid) labelled with the isotope selenium-75.\u003c\/p\u003e\n\n\u003cp\u003eHow it is done:\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003ePatients must avoid bile acid sequestrant medication for a few days before the test.\u003c\/li\u003e\n  \u003cli\u003eThey fast for four hours before swallowing the 75SeHCAT capsule.\u003c\/li\u003e\n  \u003cli\u003eA gamma camera takes the first scan within three hours of ingestion.\u003c\/li\u003e\n  \u003cli\u003eA second scan is taken after seven days, which makes the result less dependent on day-to-day diet.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eLow retention of 75SeHCAT signals fecal bile acid loss. Results are graded by how much radioactive selenium is retained:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSevere BAM:\u003c\/strong\u003e less than 5% retained\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eModerate BAM:\u003c\/strong\u003e 5% to 10% retained\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMild BAM:\u003c\/strong\u003e 10% to 15% retained\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eIn a systematic review of 43 studies enrolling 1,223 IBS patients, 10% had retention below 5%, 27% had retention below 10%, and 13% had retention below 15%.\u003c\/p\u003e\n\n\u003cp\u003eRadiation exposure is limited. The 75SeHCAT activity is small (370 KBq), the radiation dose is 0.26 mSv, and the total absorbed radiation is 0.3 Gy\/kBq. Despite its high accuracy, 75SeHCAT is not widely available and is inaccessible to most clinicians. It requires a nuclear medicine department with trained personnel and is time-consuming for the patient. These limits can lead to missed diagnoses, diagnostic delay, or unnecessary radiological and endoscopic examinations.\u003c\/p\u003e\n\n\u003ch3\u003e3. Fecal bile acid test\u003c\/h3\u003e\n\n\u003cp\u003eDirectly measuring the bile acids that reach the colon and leave in stool is an alternative when 75SeHCAT is unavailable. The protocol requires a four-day diet containing 100 g of fat, followed by a 48-hour stool collection to measure total and individual fecal bile acids.\u003c\/p\u003e\n\n\u003cp\u003eDiagnostic cut-offs:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003eTotal fecal bile acids above 2,337 µmol per 48 hours, \u003cstrong\u003eor\u003c\/strong\u003e a fraction of primary bile acids (CDCA and CA) exceeding 10% of the total\u003c\/li\u003e\n  \u003cli\u003eAn alternative recommended cut-off: total fecal bile acids above 1,000 µmol per 48 hours plus a fraction of primary bile acids exceeding 4%\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eStool frequency and consistency correlate with concentrations of primary fecal bile acids. The test is simple and safe, but both patients and healthcare workers may find it time-consuming and inconvenient. Measuring individual bile acid species is mainly reserved for research; for clinical purposes, simply measuring total fecal bile acids is considered satisfactory.\u003c\/p\u003e\n\n\u003cp\u003eReported accuracy: fecal bile acid content has 45% sensitivity and 63% specificity for detecting a 75SeHCAT result below 15% when measuring primary bile acids above 10%. It is advisable to combine the measurement of total fecal bile acid content with the percentage of primary bile acids.\u003c\/p\u003e\n\n\u003ch3\u003e4. Fasting serum C4\u003c\/h3\u003e\n\n\u003cp\u003eC4 (7α-hydroxy-4-cholesten-3-one) is the precursor of liver bile acid synthesis, so fasting serum C4 directly measures how active that pathway is. Levels above 48.9 ng\/mL can indicate BAM. The C4 and FGF19 measurements have been validated against 75SeHCAT.\u003c\/p\u003e\n\n\u003cp\u003eBecause C4 naturally fluctuates during the day, blood must be sampled before 9 a.m. False-positive or false-negative results are possible in patients with cholestatic chronic liver disease, which is liver disease with blocked bile flow. False-positive or false-negative results are also possible in patients with hypertriglyceridemia. They are also possible in people taking statins. All of these can interfere with bile acid synthesis. C4 levels can also shift with factors affecting circadian rhythm. Because of these confounders, combination testing is suggested, such as fecal bile acids plus C4 levels.\u003c\/p\u003e\n\n\u003ch3\u003e5. Fasting serum FGF19\u003c\/h3\u003e\n\n\u003cp\u003eFGF19 works in the opposite direction from C4. Low FGF19 levels mean less inhibition of the conversion of cholesterol to bile acids, while BAM diagnosis relies on decreased FGF19 and elevated C4 together. Serum FGF19 can serve as an index of ileal bile acid reabsorption. When measured in patients with chronic diarrhea, the cut-off for diagnosing BAM is a fasting FGF19 below 60 pg\/mL. Like C4, the sample should be taken in the morning while fasting.\u003c\/p\u003e\n\n\u003ch3\u003e6. Emerging diagnostic tests\u003c\/h3\u003e\n\n\u003cp\u003eNewer approaches need more validation, including machine learning techniques. Several experimental tests are in development:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003eMolecular imaging techniques to analyze how different bile acids bind to the GPBAR-1 and FXR receptors\u003c\/li\u003e\n  \u003cli\u003eSerum lipidome profiles (the pattern of fats in the blood) to distinguish people with BAM\u003c\/li\u003e\n  \u003cli\u003eDetection of microbial metabolites called volatile organic compounds (VOCs), which may mark gut dysbiosis in BAM compared with healthy people\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eVOC testing is appealing and promising, but it requires complex experimental procedures, standardization, and data analysis. The current scarcity of reliable, widely available tests is an unmet need. This is especially true when a bile acid sequestrant trial is not enough to confirm the diagnosis. It is also true when a bile acid sequestrant trial is not enough to justify using newer therapeutic agents.\u003c\/p\u003e\n\n\u003ch2 id=\"treatment\"\u003eTreatment Options for BAM\u003c\/h2\u003e\n\n\u003cp\u003eTreatment must address the underlying condition when the cause is known. When the cause is unknown, current approaches start with dietary modification and bile acid sequestrants, with newer drug classes emerging.\u003c\/p\u003e\n\n\u003ch3\u003eBile acid sequestrant therapy (BAST)\u003c\/h3\u003e\n\n\u003cp\u003eBile acid sequestrants bind bile acids in the gut so they cannot irritate the colon. This was an Italian retrospective study of chronic diarrhea in 136 patients with ileal disease, cholecystectomy, or post-prandial diarrhea. BAM was confirmed in 28.1% of cases. Patients improved after six months of treatment with cholestyramine.\u003c\/p\u003e\n\n\u003cp\u003eTreatment does more than reduce stool frequency. BAST also improves scores on the \"Role limitation due to physical health\" dimension. BAST also improves scores on the overall mental component summary of the 36-Item Short Form Survey (SF-36), a standard quality-of-life questionnaire. And notably, the review reports that about two-thirds of patients with unexplained diarrhea and confirmed BAM improved on sequestrant therapy, compared with only one-third of those without BAM.\u003c\/p\u003e\n\n\u003ch3\u003eEmerging drug treatments\u003c\/h3\u003e\n\n\u003cp\u003eBeyond bile acid sequestrants, the review highlights several therapeutic approaches now being explored. These target the specific molecular pathways that control bile acid production and recycling:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eFXR agonists\u003c\/strong\u003e — drugs that activate the farnesoid X receptor, mimicking the body's natural signal to reduce bile acid production\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eFGF19 analogues\u003c\/strong\u003e — laboratory-made versions of the hormone that tells the liver to slow bile acid synthesis\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eGLP-1 receptor agonists\u003c\/strong\u003e — drugs that mimic the gut hormone glucagon-like peptide 1\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMicrobiota modulation\u003c\/strong\u003e — treatments aimed at changing the gut bacterial community\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe authors argue that these novel agents can only make their way into routine care if BAM stops being treated as a \"diagnosis of exclusion\". A \"diagnosis of exclusion\" is a label given only after everything else has been ruled out. Ignoring BAM as a specific condition will continue to drive up healthcare costs and reduce patients' quality of life.\u003c\/p\u003e\n\n\u003ch2 id=\"implications\"\u003eWhat This Means for Patients\u003c\/h2\u003e\n\n\u003cp\u003eIf you have chronic diarrhea that has never been explained, BAM should be on your doctor's list. Between 1 in 4 and 1 in 3 people with unexplained chronic diarrhea have it, and roughly 1 in 3 people treated for IBS-D have the idiopathic form.\u003c\/p\u003e\n\n\u003cp\u003eThe condition is treatable. Bile acid sequestrants helped about two-thirds of patients with confirmed BAM in the studies reviewed, and they improve quality-of-life scores as well as stool symptoms. When BAM is absent, only about one-third of patients improve on the same therapy — which is why an accurate diagnosis matters.\u003c\/p\u003e\n\n\u003cp\u003eCertain situations raise the odds. Ask about BAM testing if you have had ileal surgery or radiation to the abdomen. Ask about BAM testing if you have Crohn's disease or celiac disease. Ask about BAM testing if you have had your gallbladder removed and developed diarrhea afterward. Ask about BAM testing if you take metformin and have developed loose stools. About 1 in 5 people on metformin show accelerated bowel transit.\u003c\/p\u003e\n\n\u003cp\u003eWatch for the red flags the review highlights as quality-of-life threats: urgency, fecal incontinence, fatigue, dizziness, and fainting feelings. These are not \"just diarrhea\" — they are the symptoms that drive depression and lost work and social time in this condition.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations of the Evidence\u003c\/h2\u003e\n\n\u003cp\u003eThe reviewers are candid about gaps in the evidence. Several key limitations stand out.\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003eNo diagnostic standardization exists for BAM, which the authors say \"may account for poor recognition and delayed management.\"\u003c\/li\u003e\n  \u003cli\u003eNo studies have compared the accuracy of empiric treatment with bile acid sequestrants against specific diagnostic testing.\u003c\/li\u003e\n  \u003cli\u003eThe most accurate test, 75SeHCAT, is unavailable to most clinicians. It requires a nuclear medicine department and trained staff, and it is time-consuming for patients.\u003c\/li\u003e\n  \u003cli\u003eFecal bile acid testing is valid but inconvenient for patients and staff, limiting real-world use.\u003c\/li\u003e\n  \u003cli\u003eC4 and FGF19 measurements can be distorted by cholestatic liver disease, hypertriglyceridemia, statin use, and circadian rhythm factors.\u003c\/li\u003e\n  \u003cli\u003eGenetic variants explain only about 1% of primary BAM cases, and the role of gut microbiota in type 2 BAM needs more research.\u003c\/li\u003e\n  \u003cli\u003eEmerging tests such as molecular imaging, serum lipidomics, and volatile organic compound detection still require validation, standardization, and better data analysis.\u003c\/li\u003e\n  \u003cli\u003eThe incidence of diarrhea after cholecystectomy ranges so widely (2% to 50%) that comparisons across studies are difficult.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eFinally, poor compliance with bile acid sequestrants is a real barrier. The medications are unpleasant to take, and that can produce false-negative results when the diagnosis rests on a treatment trial.\u003c\/p\u003e\n\n\u003ch2 id=\"recommendations\"\u003ePractical Recommendations for Patients\u003c\/h2\u003e\n\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eKeep a symptom record.\u003c\/strong\u003e Note stool frequency, urgency, incontinence episodes, fatigue, and dizziness. Correlating these with diet and stress helps your doctor judge whether BAM is likely.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk specifically about BAM testing.\u003c\/strong\u003e If you have chronic diarrhea that has not been explained, ask whether bile acid malabsorption is on the differential diagnosis. Name it — underdiagnosis is the core problem this review describes.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk whether testing is available locally.\u003c\/strong\u003e If 75SeHCAT is not accessible, alternatives include a 48-hour fecal bile acid test and fasting blood tests for C4 and FGF19.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePrepare correctly for testing.\u003c\/strong\u003e Stop bile acid sequestrants a few days before a 75SeHCAT test, fast for four hours beforehand, and have C4 or FGF19 blood drawn in the morning before 9 a.m. while fasting. For a fecal bile acid test, follow the four-day, 100 g fat diet and complete the full 48-hour stool collection.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTake a sequestrant trial seriously.\u003c\/strong\u003e If your doctor prescribes a bile acid sequestrant as a diagnostic trial, stick with it long enough to judge the response. Report side effects or difficulty taking it. Poor palatability can cause a false-negative result.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDo not accept a five-year delay.\u003c\/strong\u003e Up to half of patients wait more than five years for a BAM diagnosis. If testing is negative but symptoms persist, discuss combination testing or referral to a gastroenterologist with an interest in bile acid disorders.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about newer options.\u003c\/strong\u003e If sequestrants do not work or are poorly tolerated, ask about FXR agonists, FGF19 analogues, GLP-1 receptor agonists, and microbiome-directed approaches.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTreat the whole picture.\u003c\/strong\u003e Because BAM affects mood and daily functioning, ask about quality-of-life assessment alongside stool symptoms.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat is bile acid malabsorption (BAM)?\u003c\/h3\u003e\n\u003cp\u003eBAM means the gut does not reabsorb bile acids properly. Bile acids are detergent-like molecules the liver makes to digest fat. When too many reach the lower intestine, they trigger chronic diarrhea, sometimes called cholorrhea. Symptoms can include urgency, fecal incontinence, fatigue, dizziness, and faintness, and together these can lead to depression and reduced quality of life.\u003c\/p\u003e\n\u003ch3\u003eHow common is BAM in people with unexplained chronic diarrhea?\u003c\/h3\u003e\n\u003cp\u003eIn a US population study of patients referred to a gastroenterology outpatient clinic, BAM was found in roughly 25% to 35% of those with unexplained chronic diarrhea — between 1 in 4 and 1 in 3. About 30% of patients treated for diarrhea-predominant irritable bowel syndrome (IBS-D) have idiopathic BAM.\u003c\/p\u003e\n\u003ch3\u003eWho is at higher risk of BAM?\u003c\/h3\u003e\n\u003cp\u003eRisk is higher in people who have had ileal resection. Risk is higher in people with terminal ileal disease such as Crohn's disease or radiation-induced injury. Risk is higher in people with diseases affecting gut motility or absorption such as celiac disease. Risk is higher in people whose bile acid delivery to the small intestine is disturbed, most notably after gallbladder removal. About 1 in 5 people on metformin show accelerated bowel transit.\u003c\/p\u003e\n\u003ch3\u003eWhat tests are available for diagnosing BAM?\u003c\/h3\u003e\n\u003cp\u003eTests include an empiric trial of bile acid sequestrants, the 75SeHCAT scan, a 48-hour fecal bile acid test, and fasting blood tests for C4 and FGF19. The 75SeHCAT scan is the most accurate for identifying presence and severity, but it is not widely available. C4 and FGF19 can be distorted by liver disease, hypertriglyceridemia, statins, and circadian rhythm.\u003c\/p\u003e\n\u003ch3\u003eWhat does a 75SeHCAT result mean?\u003c\/h3\u003e\n\u003cp\u003eThe 75SeHCAT test measures how much bile acid remains in the abdomen seven days after swallowing a capsule. Results are graded by retention: severe BAM is less than 5% retained, moderate BAM is 5% to 10%, and mild BAM is 10% to 15%. Low retention signals fecal bile acid loss. The test requires avoiding bile acid sequestrants for a few days beforehand.\u003c\/p\u003e\n\u003ch3\u003eWhat treatments are available for BAM?\u003c\/h3\u003e\n\u003cp\u003eTreatment starts with dietary modification and bile acid sequestrants, which bind bile acids in the gut. In the studies reviewed, about two-thirds of patients with unexplained diarrhea and confirmed BAM improved on sequestrant therapy, compared with only one-third of those without BAM. Emerging options include FXR agonists, FGF19 analogues, GLP-1 receptor agonists, and microbiota modulation.\u003c\/p\u003e\n\u003ch3\u003eHow should I prepare for BAM testing?\u003c\/h3\u003e\n\u003cp\u003eFor a 75SeHCAT test, stop bile acid sequestrants a few days before. Fast for four hours beforehand. Expect a first scan within three hours and a second after seven days. For C4 or FGF19 blood tests, have blood drawn in the morning before 9 a.m. while fasting. For a fecal bile acid test, follow a four-day, 100 g fat diet and complete the full 48-hour stool collection.\u003c\/p\u003e\n\u003ch3\u003eI have had unexplained chronic diarrhea for years and my doctor says it is IBS. When should I seek a second opinion about bile acid malabsorption?\u003c\/h3\u003e\n\u003cp\u003eSeek a second opinion if chronic diarrhea has never been explained. Between 1 in 4 and 1 in 3 people with unexplained chronic diarrhea have bile acid malabsorption. Up to half of patients wait more than five years for the correct diagnosis. Ask specifically whether BAM is on the differential. Ask whether testing such as the 75SeHCAT scan, a 48-hour fecal bile acid test, or fasting C4 and FGF19 blood tests is available. A second opinion can confirm the diagnosis and clarify treatment options. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Advances in the pathophysiology, diagnosis and management of chronic diarrhoea from bile acid malabsorption\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Agostino Di Ciaula, Mohamad Khalil, Gyorgy Baffy, and Piero Portincasa\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthor affiliations:\u003c\/strong\u003e Clinica Medica \"A. Murri,\" Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari \"Aldo Moro,\" Medical School, Bari, Italy; Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; and Section of Gastroenterology, Department of Medicine, VA Boston Healthcare System, Boston, MA, USA.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication details:\u003c\/strong\u003e \u003cem\u003eEuropean Journal of Internal Medicine\u003c\/em\u003e, volume 128 (2024), pages 10–19. Invited Review Article. Received 25 April 2024; revised 4 July 2024; accepted 5 July 2024; available online 27 July 2024. DOI: 10.1016\/j.ejim.2024.07.008. Published as an open-access article under a CC BY license on behalf of the European Federation of Internal Medicine.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eNote:\u003c\/strong\u003e This patient-friendly article is based on peer-reviewed research. It summarizes a systematic review of published studies and is intended for educational purposes. It is not a substitute for personalized medical advice. Discuss any changes to your care with your own physician.\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47541988360348,"sku":null,"price":0.0,"currency_code":"KRW","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0599\/5449\/5644\/files\/ddn-medical-article-understanding-bile-acid-malabsorption-a-complete-guide-to-causes-diagnosis-and-treatment-of-bile-acid-related-chronic-di-hero.png?v=1790162339","url":"https:\/\/diagnosticdetectives.kr\/products\/understanding-bile-acid-malabsorption-a-complete-guide-to-causes-diagnosis-and-treatment-of-bile-acid-related-chronic-diarrhea","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}