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

Abstract

New Findings What is the topic of this review?Pathophysiological changes linked to irritable bowel syndrome (IBS) include stress and immune activation, changes in gastrointestinal microbial and bile acid profiles and sensitization of extrinsic and intrinsic gut neurons. This review explores the potential role for L‐cells in these pathophysiological changes. What advances does it highlight?L‐cells, which secrete glucagon‐like peptide‐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 that 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 bi‐directional 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 in a different manner 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. Glucagon‐like peptide‐1 can also interact with the hypothalamic–pituitary–adrenal stress axis and the 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 might be important in the manifestation of IBS symptoms. This review assesses the current knowledge about the role of GLP‐1 in IBS pathophysiology and its potential role as a signal transducer in the microbiome–gut–brain signalling axis.

The trace aminergic system: a gender-sensitive therapeutic target for IBS?

“…For example, in contrast to the over secretion of gastrin linked to TA, TAAR1 activation by a selective small molecule agonist was associated with elevated plasma levels of peptide tyrosine tyrosine (PYY) and glucagon-like peptide-1 (GLP-1) [ 186 ], which may be protective, as decreased levels of secreted PYY and GLP-1 from L-cells are implicated in IBS pathogenesis and symptomology [ 70 , 167 ]. Similarly, in terms of modulation of leukocyte responses specifically, TAAR1 is differentially expressed in several leukocyte populations, such as PMN, B and T lymphocytes, monocytes, and natural killer cells [ 8 , 56 , 160 , 214 ], thus TAAR1 activation may regulate leukocyte differentiation and activation.…”

PI 3‐kinase‐ and ERK‐MAPK‐dependent mechanisms underlie Glucagon‐Like Peptide‐1‐mediated activation of Sprague Dawley colonic myenteric neurons

“…Acting in its capacity as an incretin hormone, GLP‐1 regulates glucose homeostasis. However, GLP‐1 also exerts regulatory effects on the gastrointestinal (GI) tract, inhibiting motility, gastric emptying, and the migrating motor complex; actions that have been reported both in both healthy controls and in patients with irritable bowel syndrome (IBS) . A common, functional GI disorder, IBS is characterized by abdominal pain, bloating, diarrhea, and/or constipation.…”

“…However, GLP-1 also exerts regulatory effects on the gastrointestinal (GI) tract, inhibiting motility, gastric emptying, and the migrating motor complex; actions that have been reported both in both healthy controls and in patients with irritable bowel syndrome (IBS). [2][3][4][5] A common, functional GI disorder, 6 IBS is characterized by abdominal pain, bloating, diarrhea, and/or constipation. Administration of a GLP-1 mimetic to female patients with IBS showed efficacy in reducing spasmodic and visceral pain symptoms.…”

Role of tryptophan-metabolizing microbiota in mice diarrhea caused by Folium sennae extracts

“…genetic) and extrinsic (e.g. diet and gut microbiota) factors [16,17]. Thus, considering the effect of Folium sennae on the multiple systems of an organism, there are reasons to believe that the changes of intestinal microbiota and microbial metabolites may be a way of pharmacological mechanism of diarrhea induced by Folium sennae.…”