Effects of separate and concurrent Lactobicillus plantarum and inulin supplementation on levels of interlukin-17, interlukin-6, glial cell line-derived neurotrophic factor and Glial fibrillary acidic protein in colon and frontal cortex of male rats with type 2 diabetes

Abstract

Purpose: Type 2 diabetes mellitus (T2DM) induces gut microbial impairment and neurological disorders. The role of the gut-brain axis in the management of many diseases including T2DM has been the focus of many research activities in the recent years. However, a wide knowledge gap exists about the probiotic and/or prebiotic effects on the function of glia cells. Hence, the present study was aimed to examine the effects of separate and concurrent L.plantarum and inulin supplementation, on glia cells function in enteric and central nervous system with an inflammatory insight in T2DM. Methods: The present study was conducted on 30 Wistar rats in 5 groups: Diabetic sham group (DSh), Diabetes + L.plantarum (DL), Diabetes + Inulin (DI), Diabetes + L.plantarum + inulin (DLI), and Healthy Control (HC). After four weeks of high-fat diet, STZ was injected at 35 mg/kg to induce diabetes. Rats were treated with 107 CFU Lactobacillus (L.) Plantarum and inulin (5% of daily food weight, solved in drinking water) or their combination (Synbiotic) for eight weeks. Then, the rats were sacrificed and the colon, amygdala. and prefrontal cortex (PFC) were studied. Results: T2DM led to increased levels of glial cell line-derived neurotrophic factor (GDNF), Glial fibrillary acidic protein (GFAP), and inflammatory factors (IL-17, IL-6, and TLR-2) in the PFC (P=0.067, P<0.001, P<0.001, P=0.007, P=0.003, respectively), amygdala, and colon (P<0.001). But 8-week supplementation with inulin reduced the levels of IL-6 in the amygdala (P= 0.041) and colon (P=0.031) as well as IL-17 in the colon (P=0.047). The supplementation with L.plantarum resulted in decreased levels of IL-17 (P=0.007, P=0.040, P=0.029) and IL-6 (P=0.006, P=0.013, P=0.006) in the amygdala, PFC, and colon. Co-administration with L.plantarum and inulin resulted in reduced levels of IL-17 (P=0.002, P=0.008, P=0.006) and IL-6 (P<0.001, P=0.012, P<0.001) in the amygdala, PFC, and colon, respectively. Also, decreased levels of TRL-2 in the amygdala (P=0.029) and colon (P= 0.007) was observed in this group. In addition L.plantarum administration reduced the levels of GFAP (P= 0.014) and GDNF (P= 0.033) in the amygdala. Reduction of GFAP (P= 0.008, P= 0.004) and GDNF (P=0.036, P=0.004) levels in the amygdala and colon as well as GFAP in the PFC (P=0.027) was noticed, followed by synbiotic supplementation. There was a strong correlation of the neural and inflammatory parameters with metabolic parameters. Conclusion: According to the results, separate and concurrent L.plantarum and inulin supplementation ameliorates inflammatory state in the colon and brain. The supplementation can also improve the function of glial cells in the peripheral and central nervous system. Our findings demonstrated an innovative approach to the beneficial effects of probiotic and/or prebiotic in neuroinflammation and neurological performance, focusing on possible role of glial cells in the gut-brain axis.