Holistic perspective of the role of gut microbes in diabetes mellitus and its management

Abstract

The gut microbiota (GM) plays a role in the development and progression of type 1 and type 2 diabetes mellitus (DM) and its complications. Gut dysbiosis contributes to the pathogenesis of DM. The GM has been shown to influence the efficacy of different antidiabetic medications. Intake of gut biotics, like prebiotics, probiotics and synbiotics, can improve the glucose control as well as the metabolic profile associated with DM. There is some preliminary evidence that it might even help with the cardiovascular, ophthalmic, nervous, and renal complications of DM and even contribute to the prevention of DM. More large-scale research studies are needed before wide spread use of gut biotics in clinical practice as an adjuvant therapy to the current management of DM.

Keywords: Antidiabetic drugs; Diabetes mellitus; Microbial dysbiosis; Prebiotics; Probiotics; Synbiotics.

Figure 1

The role of gut dysbiosis in diabetes mellitus. The ingestion of a diet rich in carbohydrates and fats along with certain xenobiotics can lead to a disruption of the gut microbiome (dysbiosis). Under normal conditions, the gut bacteria produce metabolic products such as short chain fatty acids (SCFA) (Hexagons) that act locally and have a positive benefit on metabolism. Under conditions of dysbiosis there can be a disruption to the enteroendocrine cells and lead to gut permeability. This can lead to an increase in these metabolic products as well as bacterial translocation to the bloodstream, leading to endotoxemia resulting in metabolic dysfunction and insulin resistance contributing to type 2 diabetes. Gut dysbiosis also results in altered production of SCFA and release of lipopolysaccharides (LPS) (Triangles) and an increase production of other metabolites such as imidazole propionate and bacteria derived amino acids. These metabolites can act directly to affect insulin resistance. Excess SCFA and LPS can act on hepatic, skeletal, adipose, and pancreatic cells leading to metabolic dysfunction, altered inflammation and immune response which can influence insulin resistance. These factors can contribute to the development of type 1 and type 2 diabetes. SCFA: Short chain fatty acids; EEC: Enteroendocrine cells; LPS: Lipopolysaccharides; BCAA: Bacteria derived amino acids; IMP: Imidazole propionate; GM: Gut microbiota.