Bile acid malabsorption

Source: Wikipedia, the free encyclopedia.
Bile acid diarrhea / Bile acid malabsorption
Other namesBile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt diarrhea, bile salt malabsorption
Bile acid sequestrants
PrognosisGood with treatment
Frequency1 in 100 of population
DeathsNon-fatal

Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic

bile acid sequestrants
is often effective. It is recognised as a disability in the United Kingdom under the Equality Act 2010

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

colon, which causes symptoms of chronic diarrhea.[5]

Intestinal absorption of bile acids

The

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,[7] but this mutation is not more common in most patients and does not affect function.[8]

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.

bile acid sequestrants.[16] This test is not licensed in the USA, and is underutilized even where it is available.[17][18]
Older methods such as the 14C-glycocholic breath test are no longer in routine clinical use.[citation needed]

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

Cholestyramine and colestipol, both in powder form, have been used for many years. Unfortunately, many patients find them difficult to tolerate; although the diarrhea may improve, other symptoms such as abdominal pain and bloating may worsen. Colesevelam is a tablet and some patients tolerate this more easily.[26][27][28]

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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  27. ^ NICE (29 October 2013). "Bile acid malabsorption: colesevelam". Retrieved 17 August 2014.
  28. PMID 24953836
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  29. S2CID 44661338
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  30. ^ "To Assess Safety, Tolerability and Efficacy of LJN452 in Patients With Primary Bile Acid Diarrhea. - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 9 April 2018.
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  32. S2CID 250941078
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  33. PMID 38089008
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External links

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