Bacteroides uniformis CECT 7771 alleviates inflammation within the gut-adipose tissue axis involving TLR5 signaling in obese mice

Emanuel Fabersani,Kevin Portune,Sergio Montserrat-De La Paz,Marina Romaní-Pérez,Inmaculada López-Almela,Yolanda Sanz,Alfonso Benítez-Páez,Isabel Campillo

doi:10.1038/s41598-021-90888-y

Emanuel Fabersani, Kevin Portune + Show 6 more

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https://doi.org/10.1038/s41598-021-90888-y

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Abstract

This study investigated the immune mechanisms whereby administration of Bacteroides uniformis CECT 7771 reduces metabolic dysfunction in obesity. C57BL/6 adult male mice were fed a standard diet or a Western diet high in fat and fructose, supplemented or not with B. uniformis CECT 7771 for 14 weeks. B. uniformis CECT 7771 reduced body weight gain, plasma cholesterol, triglyceride, glucose, and leptin levels; and improved oral glucose tolerance in obese mice. Moreover, B. uniformis CECT 7771 modulated the gut microbiota and immune alterations associated with obesity, increasing Tregs and reducing B cells, total macrophages and the M1/M2 ratio in both the gut and epididymal adipose tissue (EAT) of obese mice. B. uniformis CECT 7771 also increased the concentration of the anti-inflammatory cytokine IL-10 in the gut, EAT and peripheral blood, and protective cytokines TSLP and IL-33, involved in Treg induction and type 2 innate lymphoid cells activation, in the EAT. It also restored the obesity–reduced TLR5 expression in the ileum and EAT. The findings indicate that the administration of a human intestinal bacterium with immunoregulatory properties on the intestinal mucosa helps reverse the immuno-metabolic dysfunction caused by a Western diet acting over the gut-adipose tissue axis.

Highlights

Obesity has become a major global health challenge due to its increasing prevalence
The oral administration of B. uniformis CECT 7771 significantly reduced body weight gain approximately by 20% (p < 0.001) at the end of the intervention in the HFHFD-fed mice, but did not modify body weight gain in the standard diet (SD)-fed mice (Fig. 1A). Consistent with these findings, visceral adipose tissue (VAT), epididymal adipose tissue (EAT) and mesenteric adipose tissue (MAT) weights were significantly lower in obese mice fed B. uniformis (HFHFD + B group) (40%; p < 0.001, 44%, p < 0.001, and 28%, p = 0.005, respectively) than in obese mice fed placebo (HFHFD group) (Fig. 1C–E)
The administration of B. uniformis CECT 7771 to HFHF-fed mice (HFHFD + B group) significantly reduced plasma cholesterol (26%, p = 0.043), triglycerides (40%, p < 0.001), glucose (27%, p = 0.026), and leptin (48%, p = 0.019) concentrations compared to obese mice fed placebo (HFHFD group) (Fig. 2A–E, G)

Summary

Introduction

Obesity has become a major global health challenge due to its increasing prevalence. In 2016, more than 1.9 billion adults (39%) 18 years and older were overweight and of these over 650 million (13%) were obese, according to the W HO1. Specific mechanisms whereby interactions between unhealthy diets and the gut microbiota contribute to metabolic inflammation include reduction in host intestinal antimicrobial peptide production, over-activation of innate immunity leading to pro-inflammatory cytokine production, and disruption of the gut barrier facilitating translocation of microbial products (e.g. LPS)[8,11,13]. This study aimed to progress in the understanding of the cellular and molecular mechanisms mediating the beneficial effects of B. uniformis CECT 7771 in the metabolic phenotype of diet-induced obese mice To this end, we have investigated the effects of the oral administration of this bacterial strain on immune cell populations and inflammatory mediators that may contribute to metabolic inflammation during obesity in the gut, peripheral blood and the adipose tissue. The possible molecular mechanisms mediating the effects related to TLR signaling and the microbiota configuration have been investigated in depth

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