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Pubmed-Ebastine for the treatment of irritable bowel syndrome: old drug, new tricks?

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Gut. 2024 Feb 1:gutjnl-2024-331927. doi: 10.1136/gutjnl-2024-331927. Online ahead of print.

There is increasing evidence that the pathophysiology of irritable bowel syndrome (IBS), once considered a functional gastrointestinal disorder and now reframed as a disorder of gut–brain interaction, has an organic basis. Some patients with IBS exhibit evidence of low-grade mucosal inflammation. One of the most well-replicated observations over the last 20 years has been reports of mast cell activation in IBS, with degranulation and a resulting increase in mucosal tryptase and histamine, as well as increased proximity of mast cells to visceral nerves, which correlate with abdominal pain severity and frequency. Colonic biopsy supernatants from patients with IBS are able to excite rat nociceptive visceral sensory nerves in vitro.

The cause of mast cell activation in this group of patients is unknown. However, evidence suggests this could relate to a break in oral tolerance to a dietary antigen, following either an acute enteric infection or a psychological stressor. In a mouse model infected with Citrobacter rodentium and exposed to a dietary antigen during the infection, an adaptive immune response to the same dietary antigen occurred during subsequent exposure. This was IgE-mediated, was gut-specific and led to diarrhoea, 

PMID:38302258 | DOI:10.1136/gutjnl-2024-331927

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