Bile acid malabsorption

Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt diarrhea or bile salt malabsorption. It can result from malabsorption secondary to gastrointestinal disease, or be a primary disorder, associated with excessive bile acid production. Treatment with bile acid sequestrants is often effective.

A persistent (chronic) history of diarrhea, with watery or mushy, unformed stools, (types 6 and 7 on the Bristol stool scale), sometimes with steatorrhea, increased frequency and urgency of defecation are common manifestations, often with fecal incontinence and other gastrointestinal symptoms such as abdominal swelling, bloating and abdominal pain.

People with this disorder often report impairments of mental health and well-being, including fatigue, dizziness, anxiety about leaving home (primarily due to fear of fecal incontinence), depression, one survey reports. It contributes in delays in diagnosis.

Bile acids (also called bile salts) are produced in the liver, secreted into the biliary system, stored in the gallbladder and are released after meals stimulated by cholecystokinin. They are important for the digestion and absorption of fats (lipids) in the small intestine. Usually over 95% of the bile acids are absorbed in the terminal ileum and are taken up by the liver and resecreted. This enterohepatic circulation of bile acids takes place four–six times in 24 hours and usually less than 0.5 g of bile acids enter the large intestine per 24 h. When larger amounts of bile acids enter the large intestine, they stimulate water secretion and intestinal motility in the colon, which causes symptoms of chronic diarrhea.

The ileum is very efficient at absorbing the glyco- and taurine-conjugated forms of the bile salts. The apical sodium-dependent bile salt transporter (ASBT, IBAT, gene symbol SLC10A2) is the first step in absorption at the brush-border membrane. The cytoplasmic ileal bile acid binding protein (IBABP, ILBP, gene symbol FABP6) and the basolateral heterodimer of OSTα and OSTβ transfer bile acids through and out of the cell where they eventually enter the portal vein. These bile acid transporters are all highly expressed in the ileum but not in the liver, jejunum or colon. When expression of these specialized transporters is reduced, the intestine is less efficient at bile acid reabsorption (Type 1 bile acid malabsorption). If intestinal motility is affected by gastro-intestinal surgery, or bile acids are deconjugated by small intestinal bacterial overgrowth, absorption is less efficient (Type 3 bile acid malabsorption). A very small proportion of the patients with no obvious disease (Type 2 bile acid malabsorption) may have mutations in ASBT, but this mutation is not more common in most patients and does not affect function.

Primary bile acid diarrhea (Type 2 bile acid "malabsorption") may be caused by an overproduction of bile acids. Several groups of workers have failed to show any defect in ileal bile acid absorption in these patients, and they have an enlarged bile acid pool, rather than the reduced pool expected with malabsorption. The synthesis of bile acids in the liver is negatively regulated by the ileal hormone fibroblast growth factor 19 (FGF19), and lower levels of this hormone result in overproduction of bile acids, which are more than the ileum can absorb.

A study found that patients suffering from bile acid diarrhea are characterized by a dysmetabolic and prediabetic-like profile, with higher postprandial concentrations of glucose, insulin and glucagon, compared with matched healthy controls. The underlying mechanisms are not fully understood. Furthermore, gut microbiome composition differs from that of people who do not suffer from bile acid diarrhea.

Several methods have been developed to identify the disorder but there are difficulties with all of them. Diagnosis of bile acid malabsorption is easily and reliably made by the SeHCAT test. This nuclear medicine test involves two scans a week apart and so measures multiple cycles of bile acid excretion and reabsorption. There is limited radiation exposure (0.3 mSv). Retention of SeHCAT at 7 days is normally above 15%; values less than 15%, 10% and 5% predict respectively mild, moderate and severe abnormal retention and an increasing likelihood of response to bile acid sequestrants. This test is not licensed in the USA, and is underutilized even where it is available. Older methods such as the ¹⁴C-glycocholic breath test are no longer in routine clinical use.