Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feeding

doi:10.1016/j.patbio.2007.09.008

Pathologie Biologie

Volume 56, Issue 5, July 2008, Pages 305-309

https://doi.org/10.1016/j.patbio.2007.09.008 Get rights and content

Abstract

A recent growing number of evidences shows that the increased prevalence of obesity and type 2 diabetes cannot be solely attributed to changes in the human genome, nutritional habits, or reduction of physical activity in our daily lives. Gut microflora may play an even more important role in maintaining human health. Recent data suggests that gut microbiota affects host nutritional metabolism with consequences on energy storage. Several mechanisms are proposed, linking events occurring in the colon and the regulation of energy metabolism.

The present review discusses new findings that may explain how gut microbiota can be involved in the development of obesity and insulin resistance. Recently, studies have highlighted some key aspects of the mammalian host-gut microbial relationship. Gut microbiota could now be considered as a “microbial organ” localized within the host. Therefore, specific strategies aiming to regulate gut microbiota could be useful means to reduce the impact of high-fat feeding on the occurrence of metabolic diseases.

Résumé

Un nombre croissant d’évidences suggère que l’augmentation de la prévalence de l’obésité et du diabète de type 2 n’est pas seulement la conséquence de modifications génétiques, d’habitudes alimentaires ou de la sédentarité. La flore intestinale joue également un rôle prépondérant dans le maintien de la santé. À ce sujet, des données récentes suggèrent que la modulation de la flore intestinale pourrait affecter le métabolisme de l’hôte et par conséquent modifier le stockage énergétique. Plusieurs mécanismes expliquent le lien entre les événements se produisant dans la partie basse de l’intestin et le maintien de l’homéostasie énergétique. Cette revue discute des découvertes récentes permettant d’expliquer comment la flore intestinale serait impliquée dans le développement de l’obésité et de l’insulinorésistance. Plus récemment, de nouvelles études ont mis en évidence les aspects moléculaires faisant le lien entre l’hôte et la flore intestinale. Dès à présent, les bactéries de l’intestin peuvent être considérées comme un véritable « organe microbien » placé au sein de l’hôte et dont les caractéristiques qualitatives et quantitatives seraient des clés de régulation du métabolisme nutritionnel. Par conséquent, les stratégies spécifiques visant à modifier la composition de la flore intestinale pourraient constituer un des moyens à notre portée afin de réduire l’impact de l’alimentation sur l’apparition des maladies métaboliques.

Introduction

Obesity and type 2 diabetes are two metabolic diseases resulting from a combination in variable association of genetic and environmental factors [1]. These two metabolic diseases are characterised by a low grade inflammation associated with the development of insulin resistance [2], [3]. Whereas the impact of a point mutation, in a key mechanism, could lead to obesity and type 2 diabetes, the molecular events allowing environmental factors to provoke the same pathological consequences, are poorly understood.

Nowadays, the growing epidemic of obesity and type 2 diabetes prompts the scientific community to develop or identify new therapeutic targets. The excessive energy intakes, as well as the reduction of physical activity, are certainly two environmental factors classically associated with the development of metabolic diseases. Among these most common triggering events, a fat-enriched diet generates features of metabolic disorders leading to the diseases.

Over the last years, numerous attempts have been performed to determine the triggering factor which (1) would depend on fat feeding, (2) trigger a low grade inflammation and (3) behave over a long term period, to be part of the progressive disease. The aim of this review is to highlight how the modulation of gut microbiota affects the development of obesity and type 2 diabetes.

Section snippets

Gut microbiota and energy metabolism

The intestinal flora has been recently proposed as an environmental factor involved in the control of body weight and energy homeostasis [4], [5], [6], [7], [8], [9]. The human intestine contains a large variety of microorganisms, this community consists of at least 10¹⁴ bacterial cells and up to 500–1000 different species. As a whole this represents overall more than 100 times the human genome [10], [11], and is called the “metagenome”. Thus, the intestinal flora can be considered as an

Gut microbiota and inflammation

Obesity and type 2 diabetes are metabolic diseased characterized by a low grade inflammation [3]. In the models of high fat diet induced obesity, adipose depots express several inflammatory factors IL-1, TNF-α and IL-6 [24], [25]. These cytokines impaired insulin action and induce insulin resistance. For example, TNF-α phosphorylates serine residue substrate (IRS-1) from the insulin receptor leading its inactivation [26]. Recently, it has been proposed that nutritional fatty acids trigger

Conclusion

The demonstration of the role of gut microflora in maintaining human health led the scientific community to consider the means by which the gut microflora could be manipulated. Different and complementary mechanisms can be proposed to explain the metabolic shift towards energy storage. The first described mechanism consists in the role of the gut microbiota to increase the capacity to harvest energy from the diet. The second one consists in the role of the gut microbiota to modulate plasma LPS

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Biological ActualityRole of gut microflora in the development of obesity and insulin resistance following high-fat diet feedingRôle de la flore intestinale dans le développement de l’obésité et de l’insulinorésistance lors d’une alimentation hyperlipidique

Abstract

Résumé

Introduction

Section snippets

Gut microbiota and energy metabolism

Gut microbiota and inflammation

Conclusion

J Nutr

Adv Appl Microbiol

Clin Chim Acta

J Lipid Res

Drug Metab Pharmacokinet

Immunity

Mechanisms linking obesity to insulin resistance and type 2 diabetes

Nature

Inflammation and metabolic disorders

Nature

Inflammation, stress, and diabetes

J Clin Invest

Microbial ecology: human gut microbes associated with obesity

Nature

An obesity-associated gut microbiome with increased capacity for energy harvest

Nature

Mechanisms underlying the resistance to diet-induced obesity in germ-free mice

Proc Natl Acad Sci U S A

Host-bacterial mutualism in the human intestine

Science

The gut microbiota as an environmental factor that regulates fat storage

Proc Natl Acad Sci U S A

Obesity alters gut microbial ecology

Proc Natl Acad Sci U S A

Evolution of Symbiotic Bacteria in the Distal Human Intestine

PLoS Biol

Inaugural Article: Honor thy symbionts

Proc Natl Acad Sci U S A

Understanding and addressing the epidemic of obesity: an energy balance perspective

Endocr Rev

Oligofructose and long-chain inulin: influence on the gut microbial ecology of rats associated with a human faecal flora

Br J Nutr

Effects of inulin on faecal bifidobacteria in human subjects

Br J Nutr

Modulation of the human gut microflora towards improved health using prebiotics–assessment of efficacy

Curr Pharm Des

Biological Actuality
Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feedingRôle de la flore intestinale dans le développement de l’obésité et de l’insulinorésistance lors d’une alimentation hyperlipidique