Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus

Abstract

Obesity and its associated disorders are a major public health concern. Although obesity has been mainly related with perturbations of the balance between food intake and energy expenditure, other factors must nevertheless be considered. Recent insight suggests that an altered composition and diversity of gut microbiota could play an important role in the development of metabolic disorders. This review discusses research aimed at understanding the role of gut microbiota in the pathogenesis of obesity and type 2 diabetes mellitus (TDM2). The establishment of gut microbiota is dependent on the type of birth. With effect from this point, gut microbiota remain quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understand these changes is important to predict diseases and develop therapies. A new theory suggests that gut microbiota contribute to the regulation of energy homeostasis, provoking the development of an impairment in energy homeostasis and causing metabolic diseases, such as insulin resistance or TDM2. The metabolic endotoxemia, modifications in the secretion of incretins and butyrate production might explain the influence of the microbiota in these diseases.

Keywords: LPS; SCFA; gut microbiota; inflammation; obesity; type 2 diabetes mellitus.

FIGURE 1

The action of gut microbiota is needed to digest some polysaccharides. Gut microbiota converts polysaccharides into monosac-charides and short-chain fatty acids (SCFA). These SCFAs are able to bind and activate two G-protein-coupled receptors (GPR41 and GPR43) of the gut epithelial cells. The activation of these receptors induces peptide YY. Starch digestion is an example of this process: H₂is produced, and its increase inhibits starch digestion, moment at which other bacterial groups work and transform the H₂ into methane.

FIGURE 2

Pathways via which intestinal microbiota can alter human metabolism producing obesity and insulin resistance. (1) Chronic bacterial translocation due to increased intestinal permeability that can drive a systemic inflammation leading to macrophage influx into visceral adipose tissue, activation of hepatic Kupffer cells and insulin resistance. (2) Short-chain fatty acids normalize intestinal permeability and alter de novo lipogenesis and gluconeogenesis via reduction of free fatty acid production by visceral adipose tissue.