Involvement of gut microbiota in association between GLP-1/GLP-1 receptor expression and gastrointestinal motility

Abstract

The microbiota in the gut is known to play a pivotal role in host physiology by interacting with the immune and neuroendocrine systems in gastrointestinal (GI) tissues. Glucagon-like peptide 1 (GLP-1), a gut hormone, is involved in metabolism as well as GI motility. We examined how gut microbiota affects the link between GLP-1/GLP-1 receptor (GLP-1R) expression and motility of the GI tract. Germ-free (GF) mice (6 wk old) were orally administered a fecal bacterial suspension prepared from specific pathogen-free (SPF) mice, and then after fecal transplantation (FT) GI tissues were obtained from the GF mice at various time points. The expression of GLP-1 and its receptor was examined by immunohistochemistry, and gastrointestinal transit time (GITT) was measured by administration of carmine red solution. GLP-1 was expressed in endocrine cells in the colonic mucosa, and GLP-1R was expressed in myenteric neural cells throughout the GI wall. GLP-1R-positive cells throughout the GI wall were significantly fewer in GF mice with FT than in GF mice without gut microbiota reconstitution. GITT was significantly shorter in GF mice with FT than in control GF mice without FT and correlated with the number of GLP-1R-positive cells throughout the GI wall. GITT was significantly longer in GF control mice than in SPF mice. When those mice were treated with GLP-1 agonist extendin4, GITT was significantly longer in the GF mice. The gut microbiota may accelerate or at least modify GI motility while suppressing GLP-1R expression in myenteric neural cells throughout the GI tract. The gut microbiota has been intensively studied, because it plays a pivotal role in various aspects of host physiology. On the other hand, glucagon-like peptide 1 (GLP-1) plays important roles in metabolism as well as gastrointestinal motility. In the present study, we have suggested that the gut microbiota accelerates gastrointestinal motility while suppressing the expression of GLP-1 receptor in myenteric neural cells throughout the gastrointestinal tract. We believe that this article is very timely and suggestive work.

Long-Lasting Effects of GSPE on Ileal GLP-1R Gene Expression Are Associated with a Hypomethylation of the GLP-1R Promoter in Female Wistar Rats

“…GLP-1 acts not only as an enteroendocrine hormone but also on the gastrointestinal tract, where it modulates gastric emptying and gut motility [29,32], thus also possibly contributing to weight loss [33]. These effects have also been attributed to GLP-1R expressed in the small intestine and colon in the myenteric neural cells [27] and smooth muscle [28]. We therefore decided to check whether a 10-day preventive treatment with GSPE was able to modulate GLP-1R in both the ileum and the colon and whether these long-lasting effects were partly modulated by epigenetics.…”

“…Moreover, possible changes in microbiota-derived products may also be responsible. Indeed, analysis of the effect of gut microbiota on GLP-1 activity revealed that gastrointestinal motility is accelerated while GLP-1R expression is suppressed in myenteric neural cells throughout the gastrointestinal tract [27]. Short chain fatty acids are also reported to induce changes in DNA methylation.…”

“…GLP-1R is expressed in the small intestine and colon, specifically in the myenteric neural cells [27] and smooth muscle cells [28]. Some effects of GLP-1, such as the modulation of gastric emptying and gastrointestinal motility, are thought to be mediated through interaction with intestinal GLP-1R [27][28][29]. However, no data are available regarding the effect of flavonoids on intestinal GLP-1R.…”

The role of the gut microbiota in the regulation of incretin effects

“…Час транзиту травним трактом був значно коротшим у мишей GF з відновленою мікробіотою, ніж у контрольних мишей GF, і корелював із кількістю GLP-1R-позитивних клітин у всій стінці травного тракту. Результати засвідчили, що мікробіота кишечнику може прискорити або принаймні змінити моторику травного тракту, пригнічуючи експресію рецепторів ГПП-1 у нервових клітинах ендотелію по всьому травному тракту [48].…”

Diabetes-induced mechanophysiological changes in the small intestine and colon

“…On other hand, it has been demonstrated that GLP-1 is progressively up-regulated in pancreatic islets during type 2 DM development[193]. More recently, the link between GLP-1/GLP-1 receptor (GLP-1R) expression and GI motility mediated by GM has been investigated[194]. They found that the expression of GLP-1R in myenteric neural cells in the GI tract was suppressed and the GI transit time became shorter in Germ-free (GF) mice after transplantation of GM.…”