Modulation of Intestinal and Systemic Inflammation by Liraglutide and Lactobacillus Plantarum Ameliorates Intestinal Dysfunction and Glucolipid Abnormalities in Diabetic Rats

Abstract Background: Enteric inflammation contributes todiabetic gastrointestinal dysfunction. Enteric dysbiosis induced by high fat diet (HFD) increases intestinal inflammation, perme-ability and absorption of bacterial lipopolysacharide (LPS). LPS promotes systemic inflammation. This results in devel-opment of diabetes. Enteric inflammation also impairs the gut-vagus nerve brain axis, responsible for insulin secretion by glucagon-like peptide-1 (GLP-1), resulting in resistance to GLP-1 agonists. GLP-1 receptors in intestinal immune cells modulate pro-inflammatory Cytokines. Probioticsenrich gut with beneficial bacteria, counteracting dysbiosis-induced inflammation. We investigated whether, modulation of intes-tinal and systemic inflammation by GLP-1 agonist liraglutide and/or lactobacillus plantarum (LP) probiotic, might ameliorate the intestinal dysfunction and glucose/lipid abnormalities indiabetic rats. Aim of Study: The aim of this study was to study the effect of Lactobacillus Plantarum alone and in combination with liraglutide to ameliorate intestinal dysfunction and glucolipid abnormalities in diabetic rats. Material and Methods: Rats were divided into: Chow fed (control, liraglutide and LP) and HFD/streptozotocin groups (control, liraglutide, LP, liraglutide/LP). Effects of4-week treatment on glucose and lipid abnormalities, intestinal per-meability and visceral hypersensitivity induced by HFD/ streptozotocinwere determined. Changes ininterleukin (IL)- 6, total antioxidant capacity, LPS and neuronal nitric oxide synthase (n NOS) were investigated. Results: HFD/streptozotocin-induced changes in glucose and lipid metabolism, intestinal permeability and visceral hypersensitivity were improved by liraglutide and LP. The drugs reduced intestinal and systemic inflammation, oxidative stress, plasma LPS and plasma/colonic IL-6. LPincreasedco-lonic nNOS and enhanced anti-diabetic and intestinal effects of liraglutide. Conclusion: Modulation of intestinal and systemic inflam-mation by liraglutide, especially when combined with probi-otics, reduces diabetic metabolic and gastrointestinal dysfunc-tion and represents a unique antidiabetic mechanism for GLP-1 agonists, besides their insulinotropic effect.
Significance statement: Modulation of intestinal and systemic inflammation by liraglutide, especially when com-bined with probiotics, reduces diabetic metabolic and gas-trointestinal dysfunction and represents a unique antidiabetic mechanism for GLP-1 agonists, besides their insulinotropic effect.