Diet Determines the Gut Microflora Diversity and Health Status

Abstract

Summary: Type 2 diabetes mellitus is a common health issue affecting millions of people worldwide. T2DM is a multi-factorial disease. It is known that gut microflora plays major role in progression T2DM. The collective human gut microflora is composed of over 35000 bacterial species. The alteration of gut microbiota due to different types of diet leads to prediseased or diseased onset by influencing the immune system and metabolic pathways. The main objective of this study was to alter the gut microbiota by administering different dis ease-induced three diets in mice (Insulin resistance, Diabetes mellitus & obesity) and to study the effect of gut microflora on, physiological parameters, various biochemical gut microbiota and its signaling pathway. Three types of different diets (High sugar diet, High fat diet and High sugar & fat diet) were given in order to check the alteration of gut microbiota. The HSD diet contained 65% fructose: sucrose; HFD diet consisted of 40% dalda while HSD+HFD diet consisted of 35% dalda and 35% sucrose: fructose. Biochemical parameters, fecal sample analysis, tissue gene expression, histopathological analysis were conducted at regular time interval & at the end of study. Results of OGTT confirmed the diabetic condition of animals & autopsy were performed of these animals. Significant increase in various biochemical parameters such as TG, glucose & cholesterol levels were seen in three treatment groups than that of control group. Increase in white adipose tissue justified weight gain in C57BL6 mice in three treatment groups when compared with control group. In histopathological analysis, damage due to inflammation was observed in liver of three treatment groups as compared to control group. Liver ChREBP, lipogenic transcription factor, increased in HSD and MIX groups along with increased TG levels in serum. Accumulation of TG elevates free fatty acid level leading to low grade inflammation by activating NF-kB and release of pro-inflammatory cytokines. Elevated Free fatty acid inhibits insulin mediated suppression of glycogenolysis, hence increasing hepatic glucose production. TNF-α, the inflammatory cytokine is up regulated while IL-10, the anti-inflammatory cytokine is down regulated in HSD, HFD and mix groups 40 | P a g e might lead to insulin resistance. Expression of PPAR-α is maximum in HFD group as it regulates the oxidative degradation of fatty acids. Expression of LXR correlates with the inhibition of gluconeogenesis in liver which is observed to be lower in HSD and higher in MIX diet. Gut microbiota alteration in HSD, HFD and MIX diet could induce inflammation and insulin resistance leading to hyperglycemia [Everard et al., 2013]. Shift in Gut microflora was observed at 90th day whereas significant change in biochemical parameters were observed at 120th day. After the microbial analysis and checking all the biochemical parameters, we conclude that gut microflora alteration leads to pre-diseased onset.