Protective effects of Bacillus probiotics against high-fat diet-induced metabolic disorders in mice.

Bobae Kim,Yosep Ji,Haryung Park,Chang-Kee Hyun,Min-Seok Kim,Jeonghyeon Kwon,Wilhelm Holzapfel,Marcia B Aguila

doi:10.1371/journal.pone.0210120

Abstract

Recently, modulation of gut microbiota by probiotics treatment has been emerged as a promising strategy for treatment of metabolic disorders. Apart from lactic acid bacteria, Bacillus species (Bacillus spp.) have also been paid attention as potential probiotics, but nevertheless, the molecular mechanisms for their protective effect against metabolic dysfunction remain to be elucidated. In this study, we demonstrate that a probiotic mixture composed of 5 different Bacillus spp. protects mice from high-fat diet (HFD)-induced obesity, insulin resistance and non-alcoholic fatty liver disease (NAFLD). Probiotic Bacillus treatment substantially attenuated body weight gain and enhanced glucose tolerance by sensitizing insulin action in skeletal muscle and epididymal adipose tissue (EAT) of HFD-fed mice. Bacillus-treated HFD-fed mice also exhibited significantly suppressed chronic inflammation in the liver, EAT and skeletal muscle, which was observed to be associated with reduced HFD-induced intestinal permeability and enhanced adiponectin production. Additionally, Bacillus treatment significantly reversed HFD-induced hepatic steatosis. In Bacillus-treated mice, hepatic expression of lipid oxidative genes was significantly increased, and lipid accumulation in subcutaneous and mesenteric adipose tissues were significantly decreased, commensurate with down-regulated expression of genes involved in lipid uptake and lipogenesis. Although, in Bacillus-treated mice, significant alterations in gut microbiota composition was not observed, the enhanced expression of tight junction-associated proteins showed a possibility of improving gut barrier function by Bacillus treatment. Our findings provide possible explanations how Bacillus probiotics protect diet-induced obese mice against metabolic disorders, identifying the treatment of probiotic Bacillus as a potential therapeutic approach.

Highlights

Overnutrition triggers excessive ectopic lipid accumulation, increases low-grade chronic inflammation and suppresses insulin signaling pathway, leading to the development of metabolic diseases such as obesity, insulin resistance, dyslipidemia and non-alcoholic fatty liver disease (NAFLD) [1]
We have previously reported that treatment of diet-induced obese (DIO) mice with a longterm fermented soybean paste (LFSP) improves non-alcoholic fatty liver disease (NAFLD) and insulin resistance, which was found to be exerted by its high bacterial content, especially Bacillus strains [12]
Mice on a high-fat diet (HFD) treated with Bacillus had significantly lower body weight gain when compared to their control (HF+PBS) mice (p < 0.05) (Fig 1A), while VSL#3-treated (HF+VSL#3) mice did not show any change in weight gain

Summary

Introduction

Overnutrition triggers excessive ectopic lipid accumulation, increases low-grade chronic inflammation and suppresses insulin signaling pathway, leading to the development of metabolic diseases such as obesity, insulin resistance, dyslipidemia and non-alcoholic fatty liver disease (NAFLD) [1]. Accumulating evidence indicate that the imbalanced gut microbiota, interacting with inflammation and lipid metabolic dysregulation, plays a key role in the development of metabolic disorders [2]. From this perspective, probiotic modulation of gut microbiota has gained their reputation as a novel approach for the prevention and treatment of immune-mediated metabolic diseases [3]. Probiotics Bacillus species being used include B. subtilis, B. cereus, B. licheniformis, B. pumilus, B. clausii, B. coagulans, B. sonorensis [6,7]. Several studies have demonstrated that Bacillus species have various probiotic activities including maintenance of intestinal homeostasis, competitive exclusion of pathogens and modulation of host immune system [8]. Probiotic Bacillus strains have been shown to possess the ability of ameliorating gut microbiota dysbiosis and inflammation [6]

Methods

Results

Conclusion