Lipopolysaccharide as a biomarker of gut dysbiosis in diabetic Wistar rats – A pre-clinical experimental study

Objectives: The increasing trend of type 2 diabetes mellitus (T2DM) poses a global health concern. The features of T2DM include hyperglycaemia and dysfunctional insulin secretion or action levels. Recent research indicates that the gut microbiota profile gets modified in diabetes. This is followed by an incremental increase in serum lipopolysaccharide (LPS) levels, which is found to have a bearing on the pathology of diabetes. LPS is a constituent of the outer wall of bacteria, particularly the Gram-negative ones. Modified gut microorganisms may interfere with intestinal barrier integrity and function, as well as host metabolic and signalling pathways. The study aimed to assess the levels of LPS as a biomarker for gut dysbiosis in diabetic adult Wistar rats. Materials and Methods: This pre-clinical, experimental study was conducted at CEFTE within the premises of the Sri Ramachandra Institute of Higher Education and Research. Institutional animal ethics committee approval was obtained. Adult male Wistar rats, 12 in number, were grouped as healthy controls (six rats) and diabetic cases (six rats). Diabetes was brought about in the case group with a high-fat diet followed by a streptozotocin injection. Plasma glucose, total cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and LPS levels were analysed. Statistical significance was considered as P ≤ 0.05. Results: Research revealed that glucose, insulin, HOMA-IR, total cholesterol and triglyceride were found to be significantly increased in diabetic rats compared to healthy rats. In a comparison of diabetic rats with non-diabetic healthy rats, there was a statistically significant increase in LPS in diabetic rats. Conclusion: Elevated LPS levels in diabetic rats suggest increased gut permeability and systemic inflammation, contributing to insulin resistance and the progression of T2DM. The study could highlight that LPS may serve as a potential biomarker for gut dysbiosis in diabetes. Further research may help explore the various molecular pathways concerned with this type of association and the various targeted therapies in handling gut dysbiosis in diabetes.