Lipopolysaccharide accelerates peristalsis by stimulating glucagon‐like peptide‐1 release from L cells in the rat proximal colon

Upon epithelial barrier dysfunction, lipopolysaccharide (LPS) stimulates glucagon‐like peptide‐1 (GLP‐1) secretion from enteroendocrine L cells by activating Toll‐like receptor 4 (TLR4). Because GLP‐1 accelerates peristalsis in the proximal colon, the present study aimed to explore whether LPS facilitates colonic peristalsis by stimulating L cell‐derived GLP‐1 release. In isolated segments of rat proximal colon that were serosally perfused with physiological salt solution and luminally perfused with 0.9% saline, peristaltic wall motion was video recorded and converted into spatio‐temporal maps. Fluorescence immunohistochemistry was also carried out. Intraluminal administration of LPS (100 or 1 µg mL−1 but not 100 ng mL−1) increased the frequency of oro‐aboral propagating peristaltic contractions. The LPS‐induced acceleration of colonic peristalsis was blocked by TAK‐242 (the TLR4 antagonist), exendin‐3 (the GLP‐1 receptor antagonist) or BIBN4096 (the calcitonin gene‐related peptide receptor antagonist). GLP‐1‐positive epithelial cells co‐expressed TLR4 immunoreactivity. In aspirin‐pretreated preparations where epithelial barrier function had been impaired, a lower dose of LPS (100 ng mL−1) became capable of accelerating peristalsis. By contrast, luminally applied dimethyl sulphoxide, a reactive oxygen species scavenger that protects epithelial integrity, attenuated the prokinetic effects of a higher dose of LPS (100 µg mL−1). In colonic segments of a stress rat model leading to a leaky gut, LPS induced more pronounced prokinetic effects. Colonic L cells may well sense luminal LPS via TLR4 triggering the release of GLP‐1 that stimulates calcitonin gene‐related peptide‐containing neurons. The resultant acceleration of peristalsis would facilitate excretion of Gram‐negative bacteria from the intestine, and thus L cells may have a protective role against intestinal bacterial infections. Key points Colonic epithelial cells form a barrier against bacterial invasion but also may contribute more actively to the exclusion of luminal pathogen by stimulating colonic motility. Luminal lipopolysaccharide (LPS) accelerated colonic peristalsis by stimulating calcitonin gene‐related peptide‐containing neurons. The prokinetic effect of LPS was mediated by the secretion of glucagon‐like peptide‐1 from enteroendocrine L cells in which Toll‐like receptor 4 was expressed. The LPS‐mediated acceleration of peristalsis depended on epithelial barrier integrity. L cells have a defe