The gut microbiota: a key regulator of metabolic diseases

Abstract

The prevalence of obesity and type 2 diabetes, two closely linked metabolic disorders, is increasing worldwide. Over the past decade, the connection between these disorders and the microbiota of the gut has become a major focus of biomedical research, with recent studies demonstrating the fundamental role of intestinal microbiota in the regulation and pathogenesis of metabolic disorders. Because of the complexity of the microbiota community, however, the underlying molecular mechanisms by which the gut microbiota is associated with metabolic disorders remain poorly understood. In this review, we summarize recent studies that investigate the role of the microbiota in both human subjects and animal models of disease and discuss relevant therapeutic targets for future research. [BMB Reports 2016; 49(10): 536-541].

Fig. 1.. Interactions between the gut microbiota and host metabolism. The gut microbiota can be influenced by a number of external factors, including host background, diet type, and medical treatments. Imbalance of the intestinal microbiota can lead to severe metabolic disorders (e.g., obesity) by altering host insulin sensitivity or energy homeostasis.

Fig. 2.. Proposed mechanism for modulation of host insulin sensitivity by Bacteroides acidifaciens (BA). The selected commensal bacterium (i.e., BA) causes intestinal epithelial cells to secrete lower amounts of dipeptidyl peptidase-4 (DPP-4) in the gut and increased levels of glucagon-like peptide-1 (GLP-1), which may contribute to glucose homeostasis. At the same time, increased levels of bile acids (i.e., cholate and taurine) may contribute to GLP-1 activation in the intestine and to peroxisome proliferator-activated receptor α (PPARα) activation through TGR5 in adipose tissues, ultimately resulting in fat oxidation and improved insulin sensitivity.