Supplementation with Sodium Butyrate Modulates the Composition of the Gut Microbiota and Ameliorates High-Fat Diet-Induced Obesity in Mice

Abstract

Short-chain fatty acids (SCFAs) have been reported to ameliorate obesity. However, the underlying mechanisms require further investigation. The aim of this study was to determine the role of butyrate, an SCFA, in the regulation of obesity, low-grade chronic inflammation, and alterations of microbiota composition in mice. Male C57BL/6J mice, 4-5 wk of age, were divided into 3 groups (n=8 mice/group): low-fat diet (LFD; 10% energy from fat), high-fat diet (HFD; 45% energy from fat), or high-fat diet plus sodium butyrate (HSB). HSB mice received sodium butyrate at a concentration of 0.1 M in drinking water for 12 wk. Measures of inflammation, obesity, and intestinal integrity were assessed. Serum lipopolysaccharide (LPS) concentrations were measured in the 3 groups. Fecal samples were collected for gut microbiota analysis. In HFD mice, body weight gain and hepatic triglyceride (TG), serum interleukin-6 (IL-6), and serum tumor necrosis factor (TNF)-α levels were 1-4 times higher than those in LFD mice (P<0.05); they were 34-42% lower in HSB mice compared with HFD mice (P<0.05). The HFD group had 28%-48% lower mRNA expression of both Tjp1 and Ocln in the ileum and colon compared with levels in LFD or HSB mice (P<0.05), whereas there was no difference in expression levels between LFD and HSB mice. Furthermore, in HSB mice, serum LPS concentration was 53% lower compared with that in HFD mice but still 23% higher than that in LFD mice (P<0.05). Results from principal component analysis showed that HSB and LFD mice had a similar gut microbiota structure, which was significantly different from that in HFD mice (P<0.05). Sodium butyrate administration beneficially changed HFD-induced gut microbiota composition and improved intestinal barrier, leading to lower serum LPS concentrations. These changes may correspond with improvements in obesity-related lipid accumulation and low-grade chronic inflammation.