A Healthy Alternative Approach for Treating Diet Induced Diabetes Using Lactobacillus Probiotic Strain

Abstract

Background: Peripheral insulin resistance is characterized by Type 2 diabetes is the most common form of diabetes. Pathways like immune and inflammatory mechanisms, involve interaction between gut microbiota and metabolic syndrome. Trillions of microbes colonize in the mammalian host, which inhabit the gastro-intestinal tract in symbiotic relationship to their host. Different dietary habits strongly influence gut microbiota composition. The alterations in microbiota population, whether chronic or acute, are accompanied with alteration in the microbiome, their patterns and specific metabolic capabilities. Bacterial secreted products reach the circulating blood, and because of that the entire bacteria products can reach tissues where inflammation is stimulated. Diabetic complications are associated with the development of obesity, insulin resistance, altered fatty acid metabolism, composition of adipose tissue and liver, increased lipopolysaccharide and increase short chain fatty acid mainly due to alteration in gut microbiota. The dysbalance of the microbiota occurs during the metabolic disorder, the therapeutic approach of restoring the gut microbiota can be by applied by using probiotics. Probiotics are live microbes that, when fed in adequate amount, results in delaying effects on diabetes development. Probiotic Lactobacillus has shown beneficial metabolic effects on gut microflora. Aim: The present study was designed to understand the gut microbiota alteration following sugar rich diet and its effect on physiology and host gene expression and probiotic application for the restoration of altered physiology and gastrointestinal immunology. In this study, the effects of Lactobacillus isolates, as probiotic strain was evaluated on insulin resistance and the immuno-modulatory activity in high sucrose fed rats. Materials and Methods: The objective of the study was to screen the characterization of the probiotic Lactobacilli isolated from the fresh yogurt. Various physiological features of the candidate probiotic isolates were primarily investigated, including tolerance to bile salts, antimicrobial activity, antibiotic susceptibility and presence of β-galactosidase. Gut microbiota, host gene expression (TLR2/TLR4) and inflammation (NF-кB) associated with Dissertation Thesis 12 high sucrose were investigated after 60 days of diet feeding. The oral glucose tolerance, fasting blood glucose, total cholesterol, triglyceride, ALT and AST was measured. The TLR2, TLR4, NLR-1, NF-кB, leptin and adiponectin mRNA expression in different tissue were also investigated. Results: The levels of fasting glucose, liver injury markers (AST and ALT), serum total cholesterol and serum TC were significantly increased in HSD rats. However, after Lactobacillus administration, the elevation of these parameters was significant suppressed. Elevated mRNA expression of TLR4, NF-кB and NLR-1 were observed in sugar fed groups. Increased inflammation was confirmed by blood biochemical assay in sugar fed diet groups. The levels of plasma glucose, liver injury markers, lipid profile in serum and liver were significantly increased in high-sucrose-fed rats. However, after Lactobacillus administration, the elevation of these parameters was significantly suppressed. Gene expression analysis revealed that in liver, small intestine, colon and adipose, the Lactobacillus restored TLR2, TLR4, NLR1 and NF-кB mRNAs toward a normal physiological level of expression. Lactobacillus is an effective in reducing the severity of liver injury, goblet cell hyperplasia and IR, ameliorated hepatic steatosis associated with HSD intake suggesting its possible therapeutic clinical utilization. Conclusion: Probiotics have wide therapeutic application. This study provided evidences clarifying the effectiveness of probiotic Lactobacillus on reducing IR, hepatic steatosis and reducing TLR4, NF-кB expression in HSD rats, which suggested that Lactobacillus can be promising therapeutic mediator in treating type 2 diabetes. Key words: Type 2 diabetes, Insulin Resistance, Gut microbiota, Probiotic, Lactobacillus, Toll like receptors, NF-кB, Sugar rich diet.