Gut microbiota and immune crosstalk in metabolic disease

Rémy Burcelin

doi:10.1016/j.molmet.2016.05.016

Abstract

BackgroundGut microbiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gut microbiota characterizes patients with obesity, type 2 diabetes, and hepatic steatosis, the mechanisms causal to the disease could be related to the translocation of microbiota from the gut to the tissues, inducing inflammation. The mechanisms regulating such a process are based on the crosstalk between the gut microbiota and the host immune system. The hologenome theory of evolution supports this concept and implies that therapeutic strategies aiming to control glycemia should take into account both the gut microbiota and the host immune system. Scope of reviewThis review discusses the latest evidence regarding the bidirectional impact of the gut microbiota on host immune system crosstalk for the control of metabolic disease, hyperglycemia, and obesity. To avoid redundancies with the literature, we will focus our attention on the intestinal immune system, identifying evidence for the generation of novel therapeutic strategies, which could be based on the control of the translocation of gut bacteria to tissues. Such novel strategies should hamper the role played by gut microbiota dysbiosis on the development of metabolic inflammation. Major conclusionsRecent evidence in rodents allows us to conclude that an impaired intestinal immune system characterizes and could be causal in the development of metabolic disease. The fine understanding of the molecular mechanisms should allow for the development of a first line of treatment for metabolic disease and its co-morbidities.This article is part of a special issue on microbiota.

Highlights

The hologenome theory of evolution proposes that natural selection acts not on the individual organism but on the “holobiont”, which consists of the host organism together with its microbiome
To design treatments for chronic, metabolic impairments, one should consider the molecular underpinnings of both the impaired microbiome and the impaired immune system The causal role of gut microbiota on metabolic diseases has been shown in rodents through microbiota transfer experiments [1] and in humans [2] demonstrating that the microbiota from a healthy donor could improve the body weight and glycemia of an obese and diabetic receiver, respectively
In HFD-induced metabolic disease we demonstrated the protective role of NOD2 in the control of glycemia and insulin resistance [18,82] and the deleterious role of NOD1 in favoring the translocation of bacteria [18]

Summary

INTRODUCTION

The hologenome theory of evolution proposes that natural selection acts not on the individual organism but on the “holobiont”, which consists of the host organism together with its microbiome (its genes and metabolites). Specificity, swiftness, and a memory to the dysbiotic microbiome This crosstalk could be the first concept integrating the impact of the environment (social, nutritional, chemical, and behavioral) with the genetic of the host to explain the diversity and the development of metabolic disease in light of the definition of the holobiont. It will aim to promote the concept that the development and treatment of metabolic disease should take into consideration that the holobiont, including the microbiome and immune system as the master regulatory mechanism, is a complex organism adapted to the environment. The threshold of a given molecular mechanism of the microbiome to host crosstalk, classifying individuals in a state of health or of metabolic disease, should always be considered for a specific homogeneous group of individuals in a specific environment. Classifying biomarkers and tailoring medicine/nutrition strategies should be based on an understanding of the adaptation of the holobiont e the host, its immune system, and its microbiome

METABOLIC DISEASE

Findings

CONCLUSION