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

J Nutr. 2019 May 1;149(5):747-754. doi: 10.1093/jn/nxy324.


Background: Short-chain fatty acids (SCFAs) have been reported to ameliorate obesity. However, the underlying mechanisms require further investigation.

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: butyrate; gut microbiota; inflammation; lipopolysaccharide; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butyric Acid / pharmacology
  • Butyric Acid / therapeutic use*
  • Colon / drug effects
  • Colon / metabolism
  • Colon / microbiology
  • Diet, High-Fat*
  • Dietary Fats / adverse effects
  • Dietary Fats / blood
  • Dietary Supplements*
  • Dysbiosis / etiology
  • Dysbiosis / prevention & control
  • Gastrointestinal Microbiome / drug effects*
  • Ileum / drug effects
  • Ileum / metabolism
  • Inflammation / blood
  • Inflammation / etiology
  • Inflammation / prevention & control
  • Interleukin-6 / blood
  • Intestines / drug effects*
  • Intestines / microbiology
  • Lipids / blood
  • Lipopolysaccharides / blood
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice, Inbred C57BL
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Obesity / microbiology
  • Obesity / pathology
  • Occludin / metabolism
  • Triglycerides / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • Weight Gain / drug effects
  • Zonula Occludens-1 Protein / metabolism


  • Dietary Fats
  • Interleukin-6
  • Lipids
  • Lipopolysaccharides
  • Occludin
  • Ocln protein, mouse
  • Tjp1 protein, mouse
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Zonula Occludens-1 Protein
  • Butyric Acid