Endocrine regulation of gut function – a role for glucagon‐like peptide‐1 in the pathophysiology of irritable bowel syndrome

New Findings

Pathophysiological changes linked to Irritable Bowel Syndrome (IBS) include stress and immune activation, changes in gastrointestinal microbial and bile acids profiles and sensitisation of extrinsic and intrinsic gut neurons. This review explores the potential role for L‐cells in these pathophysiological changes. L‐cells, which secrete glucagon‐like peptide‐1 (GLP‐1) in response to nutrients, microbial factors, bile acids and short‐chain fatty acids, may sense IBS‐related changes in the luminal environment. Glucagon‐like peptide 1 can act as a hormone, a paracrine factor or a neuromodulatory factor and through its actions on central or peripheral neurons, may play a role in gastrointestinal dysfunction.

Abstract

The prevalent and debilitating functional bowel disorder Irritable Bowel Syndrome (IBS), is characterized by symptoms which include abdominal pain, bloating, diarrhoea and/or constipation. The heterogeneity of IBS underscores a complex multifactorial pathophysiology, which is not completely understood, but involves dysfunction of the bidirectional signalling axis between the brain and the gut. This axis incorporates efferent and afferent branches of the autonomic nervous system, circulating endocrine hormones and immune factors, local paracrine and neurocrine factors and microbial metabolites. L‐cells, which are electrically excitable biosensors embedded in the gastrointestinal epithelium, secrete glucagon‐like peptide‐1 (GLP‐1) in response to nutrients in the small intestine. However, they appear to function differently more distally in the gastrointestinal tract, where they are activated by luminal factors including short‐chain fatty acids, bile acids and microbial metabolic products, all of which are altered in IBS patients. GLP‐1 can also interact with the hypothalamic‐pituitary‐adrenal stress axis and immune system, both of which are activated in IBS. Given that a GLP‐1 mimetic has been found to alleviate acute pain symptoms in IBS patients, GLP‐1 may be important in the manifestation of IBS symptoms. This review assessed the current knowledge on the role of GLP‐1 in IBS pathophysiology and its potential role as a signal transducer in the microbiome–gut‐brain signalling axis.

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