Intestinal microbiota mediates the beneficial effects of n-3 polyunsaturated fatty acids during dietary obesity,

Jérôme Bellenger,Michel Narce,Quentin Escoula,Sandrine Bellenger,Pierre Weill,Amina Bourragat

doi:10.1051/ocl/2021006

Abstract

Obesity, now considered as a real worldwide epidemic affecting more than 650 million people, is complex and mainly associated with excessive energy intake and changes in eating habits favoring the consumption of diets rich in saturated fat and sugar. This multifactorial pathology is linked to chronic low grade systemic inflammation. Indeed, a high fat diet (HFD) leads to intestinal microbiota dysbiosis increasing gut permeability (partly attributed to a downregulation of genes encoding tight junction proteins) leading to an increase in bacterial lipopolysaccharides (LPS) levels so-called metabolic endotoxemia. Studies have shown that n-3 polyunsaturated fatty acids (PUFAs) are involved in the prevention of obesity and insulin resistance partly through synthesis of lipid mediators. While studies suggest that n-3 PUFAs are able to modulate the gut microbiota, others show no effect of n-3 treatments on intestinal homeostasis. In the present work, we showed that when fed a hypercaloric and obsogenic diet, compared with wild-type (WT) mice, fat-1 mice (with constitutive production of n-3 PUFAs) resist to dietary obesity and associated metabolic disorders, maintain an effective gut barrier function and exhibit greater phylogenic diversity. Moreover, fecal microbiota transplantation from fat-1 to WT mice reversed body weight gain, normalized glucose tolerance and intestinal permeability in association with prevention of alteration of the colon mucus layer. We can conclude that the n-3 PUFA-mediated alterations of gut microbiota contribute to the prevention of metabolic syndrome in fat-1 mice and may represent a promising strategy to prevent metabolic disease and preserve a lean phenotype.

Highlights

Nowadays, overweight and obesity is a major public health problem in both industrialised and major developing countries
A study has evidenced opposite effects of n-6 and n-3 polyunsaturated fatty acids (PUFAs) on metabolic endotoxemia, depending on the hostmicrobiota relationship (Kaliannan et al, 2015). These studies, focusing on these issues, confirm that a link exists between the dietary FA content and their impact on gut microbiota. These results reveal that the modulation of the gut barrier function by n-3 PUFA still remains poorly understood and that the means by which these fatty acids are able to fight against the increase of gut permeability, observed in a context of dietary obesity, still requires further studies
Microbiota is known to be a major player in intestinal and energy homeostasis (Backhed et al, 2004), we studied its involvement in the preventive effects of n-3 LCPUFA in fat-1 mice during obesity and associated alteration

Summary

Introduction

Overweight and obesity (a complex pathology associated with numerous metabolic disorders) is a major public health problem in both industrialised and major developing countries. It has been observed in mice that the infusion of LPS for 4 weeks mimics the inflammatory metabolic effects induced by consumption of a high-fat and high-calorie diet (Cani et al, 2007) Numerous studies, both in human and animal, have shown that dietary n-3 PUFA are able to participate in the prevention of obesity and insulin resistance notably through the production of pro-resolving lipid mediators (White and Marette, 2014). We have shown that the transfer of fat-1 microbiota protects wild-type mice against weight gain and metabolic and intestinal alterations elicited by 18 weeks of highfat high-calorie diet (Bidu et al, 2018) These microbiota transfer experiments led us to demonstrate the preventive effects of intestinal microbiota modulated by n-3 LCPUFA in dietinduced obesity and associated metabolic disorders (Fig. 1)

N-3 PUFA and colonic mucus

Findings

Conclusion