Evaluating the Immunological Environment of Liver and its Metabolic Shift following Gut microbiota Alteration in Diet Induced Type 2 Diabetes

Abstract

Gut microflora alteration in type 2 diabetes condition is a healthy approach to cure. Type 2 diabetes (T2D) is multi-dysfunctional disorder involves metabolic and immunological disorders which is now well known that linked to altered gut microflora. The spread of microbiota over GI track is different and each region has specific micro-environment and output. It is a well-known fact that due to high energy diet gram-negative population increases, consequently LPS in serum also increases which lead to systemic inflammation. With the pilot study done using Gram-negative, Gram-positive and broad-spectrum antibiotic same was observed. So, further experiments were done using cefdinir, a Gram-negative antibiotic. To understand the major source of LPS and the role of the microbiota of the SI and colon region, formulation of cefdinir was prepared using pH specific polymer which gives target specific release of cefdinir. Rats were fed 65% carbohydrate-rich diet along with Gram-negative antibiotic and its formulation to check its preventive efficacy and it was found that due to the effect of the antibiotic, growth of Gram-negative microflora was prevented and thus it delayed/ prevented animals to become diabetic. In another study done with mice, which were also fed with 65% carbohydrate-rich diet and given antibiotic as treatment strategies i.e., antibiotic and its formulations were given after the diabetic progression in animals. Here we found that the effect of antibiotic here is killing of Gram-negative and thus reduced pathogenesis of T2D and increased insulin sensitivity in the liver. T cell phenotyping in the liver revealed that the nature of inflammation in the liver is different from spleen and mesenteric lymph node during T2D. Microflora alteration in colon successively alters liver Th17/Treg ratio and also helps in regulating metabolism. Here, we conclude that colonic bacteria are the important bacteria and location to target to overcome T2D pathogenesis and improve insulin sensitivity. They can be tar