Insights Into the Role of the Microbiome in Obesity and Type 2 Diabetes

Annick V. Hartstra; Kristien E.C. Bouter; Fredrik Bäckhed; Max Nieuwdorp

Disclosures

Diabetes Care. 2015;38(1):159-165. 

In This Article

Abstract and Introduction

Abstract

The worldwide prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise at an alarming pace. Recently the potential role of the gut microbiome in these metabolic disorders has been identified. Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome seems to be more efficient in harvesting energy from the diet. Lean male donor fecal microbiota transplantation (FMT) in males with metabolic syndrome resulted in a significant improvement in insulin sensitivity in conjunction with an increased intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains. Such differences in gut microbiota composition might function as early diagnostic markers for the development of T2DM in high-risk patients. Products of intestinal microbes such as butyrate may induce beneficial metabolic effects through enhancement of mitochondrial activity, prevention of metabolic endotoxemia, and activation of intestinal gluconeogenesis via different routes of gene expression and hormone regulation. Future research should focus on whether bacterial products (like butyrate) have the same effects as the intestinal bacteria that produce it, in order to ultimately pave the way for more successful interventions for obesity and T2DM. The rapid development of the currently available techniques, including use of fecal transplantations, has already shown promising results, so there is hope for novel therapies based on the microbiota in the future.

Introduction

The rising prevalence of type 2 diabetes mellitus (T2DM) continues to be a growing concern worldwide. From 1980 to 2008 the number of people diagnosed with diabetes, of which 90% type 2, has increased from 153 (123–182) million to 347 (314–382) million.[1] The proportional increase in prevalence of obesity (between 1980 and 2008, this has nearly doubled to more than half a billion people in the world) shows weight gain and changes in dietary habits to be the main contributing factors to this alarming trend. The resulting metabolic disorders like dyslipidemia and insulin resistance, both part of the metabolic syndrome, are a major risk factor for associated diseases such as cardiovascular pathology, nonalcoholic fatty liver disease, and different types of cancer.[2,3] The main cause for the obesity and diabetes epidemic has been attributed to economic and lifestyle changes in the last decades, including the decrease in physical activity combined with a growing availability of food high in calories. However, it appears to be extremely difficult for people to voluntarily change their lifestyle drastically in order to lose weight. In this respect, evidence of a powerful regulating biological system resisting these cognitive signals in order to maintain body weight in a relatively strict range is substantial and growing.[4] For this reason, obesity is now considered a disease, rather than a willful choice, which calls for further insight into the pathophysiological pathways, as this could lead to sorely needed novel therapeutic targets.

A recently discovered partaker in this process is the intestinal microbiome.[2] The microbiome refers to the >1014 bacteria that reside in the human intestine, comprising a bulk of genetic material larger than the human genome.[5] Recently our knowledge of the microbiome in relation to the function of the human (small) intestine (Fig. 1)[6] has increased immensely due to the development of new analytical methods such as high-throughput metagenomic sequencing.[7] This has enabled researchers to identify possible effects of the microbiome on human metabolism, including its potential role in metabolic disorders like obesity and T2DM. In this review, we aim to provide deeper insight of relevance to clinicians by discussing several topics in a "bench to bedside" approach within this emerging field.

Figure 1.

Differential functions of small and large intestine in relation to microbial density.6 In the proximal part of the small intestine (where only few intestinal bacterial strains reside), important metabolic functions take place such as uptake of dietary glucose, lipids, and proteins. More distally in the colon (where the majority of intestinal bacterial strains reside), water is absorbed from feces and SCFAs are produced via fermentation.

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