Bile acid malabsorption
Bile acid diarrhea / Bile acid malabsorption | |
---|---|
Other names | Bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt diarrhea, bile salt malabsorption |
Bile acid sequestrants | |
Prognosis | Good with treatment |
Frequency | 1 in 100 of population |
Deaths | Non-fatal |
Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic
Signs and symptoms
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.[2][3][1][4]
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.[1] It contributes in delays in diagnosis.[1]
Pathogenesis
Enterohepatic circulation of bile salts
Intestinal absorption of bile acids
The
Overproduction of bile acids
Primary bile acid diarrhea (Type 2 bile acid "malabsorption") may be caused by an overproduction of bile acids.[5][9] 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.[10] 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.[9]
Dysmetabolism and gut microbiome
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.[11] The underlying mechanisms are not fully understood. Furthermore, gut microbiome composition differs from that of people who do not suffer from bile acid diarrhea.[12][13][14]
Diagnosis
Several methods have been developed to identify the disorder but there are difficulties with all of them.
Measurement of 7α-Hydroxy-4-cholesten-3-one, (C4), a bile acid precursor, in serum, shows the increased bile acid synthesis found in bile acid malabsorption.[19] This test is an alternative diagnostic means when available. Fasting blood FGF19 values may have value in the recognition of the disease and prediction of response.[20]
The various biomarkers give similar diagnostic yields of around 25% in patients with functional bowel disorders with diarrhea.[21] In countries such as the US, where SeHCAT is not available, fecal bile acids and C4 are available to make the diagnosis.[21]
Classification
Bile acid malabsorption was first recognized in patients with ileal disease.[22] When other causes were recognized, and an idiopathic, primary form described,[23] a classification into three types was proposed:[24]
- Type 1: Bile acid malabsorption, secondary to ileal resection, or ileal inflammation (e.g. in Crohn's disease)
- Type 2: Idiopathic bile acid malabsorption, Primary bile acid diarrhea
- Type 3: Secondary to various celiac disease, chronic pancreatitis, etc.
Treatment
A proof of concept study of the farnesoid X receptor agonist obeticholic acid has shown clinical and biochemical benefit.[29]
As of March 15, 2016, Novartis Pharmaceuticals is conducting a phase II clinical study involving a farnesoid X receptor agonist named LJN452.[30]
A study from 2022, inspired by clinical cases [31] showed superiority in favour of the GLP-1 receptor agonist Liraglutide compared with Colesevelam in reducing stool frequency in patients suffering from bile acid diarrhoea, suggesting Liraglutide as a new, safe and more effective treatment compared with the commonly known treatment modalities.[32]
Epidemiology
Bile acid malabsorption is common in Crohn's disease but not always recognized. Most people with previous ileal resection and chronic diarrhea will have abnormal SeHCAT tests and can benefit from bile acid sequestrants.[4]
People with primary bile acid diarrhea are frequently misdiagnosed as having irritable bowel syndrome.[17] When SeHCAT testing is performed, the diagnosis of primary bile acid diarrhea is commonly made. In a review of 18 studies of the use of SeHCAT testing in diarrhea-predominant irritable bowel syndrome patients, 32% of 1223 people had a SeHCAT 7-day retention of less than 10%, and 80% of these reported a response to cholestyramine, a bile acid sequestrant.[16]
A study from 2023 investigating the epidemiology of bile acid diarrhea in Denmark, found that people suffering from bile acid diarrhea seemed to have more co-morbidities, lower levels of income and education and more health care contacts compared with matches not suffering from bile acid diarrhea.[33]
Estimates of the population prevalence suggest that 1% of the adult population could have primary bile acid diarrhea (Type 2 bile acid malabsorption).[16]
References
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