Highly Branched Neo-Fructans (Agavins) Attenuate Metabolic Endotoxemia and Low-Grade Inflammation in Association with Gut Microbiota Modulation on High-Fat Diet-Fed Mice.

Alicia Huazano-García,Argel Gastelum-Arellanez,Lino Sánchez-Segura,Mercedes G López,María Blanca Silva-Adame,Juan Vázquez-Martínez

doi:10.3390/foods9121792

Abstract

Highly branched neo-fructans (agavins) are natural prebiotics found in Agave plants, with a large capacity to mitigate the development of obesity and metabolic syndrome. Here, we investigated the impact of agavins intake on gut microbiota modulation and their metabolites as well as their effect on metabolic endotoxemia and low-grade inflammation in mice fed high-fat diet. Mice were fed with a standard diet (ST) and high-fat diet (HF) alone or plus an agavins supplement (HF+A) for ten weeks. Gut microbiota composition, fecal metabolite profiles, lipopolysaccharides (LPS), pro-inflammatory cytokines, and systemic effects were analyzed. Agavins intake induced substantial changes in gut microbiota composition, enriching Bacteroides, Parabacteroides, Prevotella, Allobaculum, and Akkermansia genus (LDA > 3.0). l-leucine, l-valine, uracil, thymine, and some fatty acids were identified as possible biomarkers for this prebiotic supplement. As novel findings, agavins supplementation significantly decreased LPS and pro-inflammatory (IL-1α, IL-1β, and TNF-α; p < 0.05) cytokines levels in portal vein. In addition, lipid droplets content in the liver and adipocytes size also decreased with agavins consumption. In conclusion, agavins supplementation mitigate metabolic endotoxemia and low-grade inflammation in association with gut microbiota regulation and their metabolic products, thus inducing beneficial responses on metabolic disorders in high-fat diet-fed mice.

Highlights

The incidence of obesity worldwide has increased drastically in the last decade reaching pandemic proportions and significantly contributing to reducing the life quality of people
Since the intake of high-fat diets is associated with reduced bacterial diversity in the cecal microbiota [33]; in addition, prebiotics supplements usually promote the growth of specific bacterial taxa [34,35]
Agavins supplementation induced substantial changes in the gut microbiota composition as well as in the microbial metabolite profiles, which strongly suggests a switch of microbial metabolism toward the utilization of indigestible carbohydrates; these new data could be consumption could be a very good dietary strategy to prevent or mitigate some problems associated with the metabolic syndrome derived from high-fat diet consumption [15,16,17]

Summary

Introduction

The incidence of obesity worldwide has increased drastically in the last decade reaching pandemic proportions and significantly contributing to reducing the life quality of people. Environmental factors, such as high-fat diet consumption and a sedentary lifestyle are the main causes of this dramatic obesity increment [1]. In several mice studies it has been reported that high-fat diet consumption end up in gut dysbiosis (alterations in gut microbiota composition), commonly defined by an increase of Firmicutes and decrease of Bacteroidetes [4]; this gut dysbiosis leads to lipopolysaccharide (LPS, important constituent of the outer membrane of Gram-negative bacteria) release to the bloodstream, due to increase intestinal permeability, this process has been referred to as metabolic endotoxemia and related to the development of low-grade inflammation [5,6]

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Conclusion