Good news!
"However, around one person in every 100 is affected by a condition known as bile acid diarrhoea (also known as bile acid malabsorption), whereby the bile acid is not properly re-absorbed and makes its way into the large intestine (colon). It can trigger urgent and watery diarrhoea, and patients can risk episodes of incontinence.
Bile acid diarrhoea can be difficult to diagnose as there are currently no routine clinical blood tests. Many individuals are given a diagnosis of irritable bowel syndrome (IBS), an umbrella term for a range of conditions. As many as one in 20 people is thought to have IBS, of which an estimated one in three patients with diarrhoea as their main symptom have undiagnosed bile acid diarrhoea.
Studies in mice have previously suggested that the gut hormone known as Insulin-Like Peptide 5 (INSL5) – present in cells at the far end of the colon and rectum – may play a role in chronic diarrhoea. INSL5 is released by these cells when irritated by bile acid.
Researchers ... have been exploring whether this hormone might also underlie chronic diarrhoea in humans. This has been possible thanks to a new antibody test ... which allows them to measure tiny amounts of INSL5.
A study ... looking at ways to trigger release of the gut hormone GLP-1 – the hormone upon which weight-loss drugs are based – previously found that giving a bile acid enema to healthy volunteers triggered release of GLP-1, but had the unintended consequence of causing diarrhoea. When the ... team analysed samples from this study, they found that the bile acid enema caused levels of INSL5 to shoot up temporarily – and the higher the INSL5 levels, the faster the volunteers needed to use the toilet. This confirmed that INSL5 is likely to play a role in chronic cases of diarrhoea.
When the team analysed samples ... which include samples from patients with bile acid diarrhoea, they found that while levels of INSL5 were almost undetectable in healthy volunteers, they were much higher in patients with bile acid diarrhoea. In addition, the higher the INSL5 level, the more watery their stool samples. ..."
From the abstract:
"Background
Insulin-like peptide 5 (INSL5) is an enteroendocrine hormone expressed in distal colonic ‘L cells’. Bile acid receptor agonists are known to stimulate INSL5 secretion in primary cell culture, and administration of an INSL5 analogue in animals promotes colonic motility.
Objective
This study used a new immunoassay to measure INSL5 in human blood samples, enabling assessment of whether rectal bile acids stimulate INSL5 release in humans and whether INSL5 levels are altered in patients with chronic diarrhoea.
Design
Serum/plasma samples from previously performed studies were used, including healthy volunteers (n=7) who received a rectal enema of taurocholic acid (TCA); fasting and post prandial samples from healthy volunteers (n=10); patients with bile acid diarrhoea (BAD) (n=19) or irritable bowel syndrome with diarrhoea (IBS-D) (n=8); and patients with IBS-D (n=64) treated with ondansetron or placebo.
Results
Rectal TCA but not a control enema promptly elevated plasma INSL5, with the increase in INSL5 correlating negatively with time to, and positively with desire to, defecate post enema.
Healthy volunteers had low INSL5 levels (<100 pg/mL), with no change following a mixed meal.
Patients with BAD had elevated INSL5 levels, with average stool consistency being positively correlated with serum INSL5 (p<0.001). In people with IBS-D, INSL5 was elevated (>100 pg/mL) in 42%, and this subgroup showed greater improvements in stool consistency with ondansetron therapy (p<0.05).
Conclusion
The study highlights that rectal bile acids stimulate INSL5 secretion in humans, and that INSL5 levels are associated with a colonic pro-motility response and pathophysiology of chronic diarrhoea."
No comments:
Post a Comment