Elucidating the Role of Pathogen Pattern Recognition Receptors and Inflammatory Mediators following Gut Microbiota alteration and in Diet induced Type 2 Diabetes

Abstract

Sugar rich diet induces inflammation and insulin resistance (IR) mainly newlinethrough gut microbiota alteration. Gut microflora dysbiosis increases lipopolysaccharide newline(LPS) and reduces the short chain fatty acids (SCFAs) levels to impair the insulin signaling newlinecascades by different molecular pathways, which progresses into IR. This study was designed newlineto investigate the effect of spectrum specific antibiotics and chitosan administration on gut newlinemicroflora mediated signaling pathways to prevent the diet induced diabetes. newlineMethods: Healthy male wistar rats were divided into non-diabetic group with a normal diet newline(CD), diabetic group with high sucrose diet (HSD) and three antibiotics and chitosan newlineadministrated groups along with HSD. The effect of their administration was studied at newlinephysiological, biochemical, inflammatory and molecular levels. Further, effect of altering the newlinetarget specific microbial population was studied in context with insulin sensitivity. newlineResults and Conclusion: After 12 weeks of the study, significant alterations in three major newlinegut dominant microbial phyla i.e Firmicutes, Bacteroides and Proteobacteria along with four newlinegenera i.e. Lactobacilli, Bifidobacteria, Escherichia and Clostridia were observed in all the newlineexperimental groups. Cefdinir administration in HSD had significantly reduced the fasting newlineglucose, serum triglycerides and cholesterol levels compared to HSD control. It had reduced newlinethe metabolic endotoxemia by decreasing the population of Gram negative phyla, i.e. newlineBacteroidetes and Proteobacteria in the gut. Reduced endotoxin levels had decreased the newlinemRNA expression of TLR4 and NLR1, which further downregulated the NF-and#954;B activity to newlinedecrease the expression of proinflammatory cytokines. Chitosan administration in HSD had newlineincreased the population of Lactobacilli and Bifidobacteria with a decrease in Escherichia newlineproving its prebiotic properties. Cefdinir and chitosan receiving animals had shown significant newlineincrease in the major SCFAs, such as butyrate and propionate level, while decrease