Using Short Chain Fatty Acids (SCFAs) as a Novel Treatment Stretegy For Type II Diabetes

Abstract

INTRODUCTION: There are different type of short chain fatty acids (SCFAs) but Acetate, Butyrate and propionate are most abundant in the GI tract. SCFAs are microbial product of gut microbiota from the unabsorbed and undigested carbohydrate in large bowl by anaerobic digestion. In a control group the ratio of the most abundant SCFAs i.e., Acetate: Propionate: Butyrate is 60:20:20 in large intestine. In the previous study from our lab, diet induced diabetic group of animals showed alteration in their gut microflora and ratio of their microbial products, i. e. SCFAs. HYPOTHESIS: Following diet induce diabetes in mice there is an alteration in their SCFAs. Can administration of these SCFAs individually restore the balance and other altered parameters? OBJECTIVE The project was aimed to investigate the anti-diabetic role of SCFAs and to understand the gut microflora alteration following treatment with different SCFAs and its receptor. DESIGN: The male mice were divided into two different groups: control group (control diet) and Diabetic or High Sugar Diet fed group. Following 120 days of oral dietary uptake and after confirmation based on oral glucose tolerance test assay (OGTT), diabetes was conformed in HSD group. HSD group was further divided in to four sub group. First HSD sub group served as HSD animal were sacrificed and blood, fecal and all tissue were collected and processed for serum biochemistry, fecal microfloral quantification and tissue gene expression analysis respectively. The remaining three groups were treated with Acetate, Propionate and Butyrate individually. After 30 days of treatment all animals were sacrificed and blood, fecal and tissue was collected and used for all the parameters same as that after HSD group. RESULT: HSD group have significantly increased all biochemical parameter such as SGOT, SGPT, FFAs, cholesterol and triglyceride level have been observed. Altered expression of TLRs indicate the gut microflora alteration. Glucose and fructose metabolism alteration also proved by altered SREBP, CHREBP and LXR. Rather then group of treatment significantly altered all biochemical parameters such as SGOT, SGPT, FFAs, and cholesterol and triglyceride level have been observed individually. There are altered gene expression observed in all treatment group. CONCLUSION: Propionate play crucial role in restoration of gut microbiota has been proved by TLRs expression. Higher Insulin sensitivity is observed in butyrate and propionate rather than acetate and HSD group. It conclude that propionate and acetate have more significant effect rather than butyrate in diabetes.