Effect of exercise and butyrate supplementation on microbiota composition and lipid metabolism

Abstract

The composition and activity of the gut microbiota depend on the host genome, nutrition, and lifestyle. Exercise and sodium butyrate (NaB) exert metabolic benefits in both mice and humans. However, the underlying mechanisms have not been fully elucidated. This study aimed to examine the effect of exercise training and dietary supplementation of butyrate on the composition of gut microbiota and whether the altered gut microbiota can stimulate differential production of short-chain fatty acids (SCFAs), which promote the expression of SESN2 and CRTC2 to improve metabolic health and protect against obesity. C57BL/6J mice were used to study the effect of exercise and high-fat diet (HFD) with or without NaB on gut microbiota. Bacterial communities were assayed in fecal samples using pyrosequencing of 16S rRNA gene amplicons. Western blot was performed using relevant antibodies to detect the protein expressions in liver and HepG2 cell extracts. Exercise and butyrate administration significantly reversed metabolic dysfunctions induced by HFD (P < 0.05). The number of Firmicutes and the proportion of Firmicutes to Bacteroidetes order were predominant in all HFD groups (P = 0.001). Exercise and butyrate supplementation significantly inhibited the relative abundance of lipopolysaccharide-producing phyla (P = 0.001). SESN2 and CRTC2 expression in the liver of mice were significantly increased after exercise (P < 0.05) and/or supplementation of butyrate (P < 0.05). Exercise enhances butyrate-producing fecal bacteria and increases butyrate production and consequently improves lipid metabolism through the butyrate-SESN2/CRTC2 pathway. Excess butyrate may reduce the proportion of probiotics and reverse the metabolic effects.

The Impact of Microbiome and Microbiota-Derived Sodium Butyrate on Drosophila Transcriptome and Metabolome Revealed by Multi-Omics Analysis

“…The negative correlation between these two types of bacteria and antimicrobial peptide genes IM2 , IM3, and DptA ( Figure 7 A) could also support the effect of sodium butyrate on Acetobacter and Lactobacillus . The metabolites composition in our study showed that sodium butyrate supplement can dramatically cause lipid accumulation ( Figure 6 ); this is also consistent with the previous report that sodium butyrate can regulate lipid metabolism [ 25 , 26 ]. Our work can serve as launching points for future work, and additional investigations are warranted to understand the effects of sodium butyrate on host metabolism, including the specific functions of differentially expressed genes in Drosophila .…”

Association between physical activity and changes in intestinal microbiota composition: A systematic review

“…It is still unclear whether an active lifestyle, a healthy diet, or a combination of both can influence intestinal microbiota towards a healthy state. Animal models have allowed researchers to develop physiological and biochemical protocols [28][29][30][31][32][33][34][35][36][37][38] to explore the functional effects of exercise on the microbiome [37,39,40], and cross-sectional and longitudinal studies have tried to describe the effects of physical activity on the microbiome composition of active versus non-active adult humans. The heterogeneity of methodological approaches and the lack of standardized criteria for active/non-active people is one of the largest challenges in this research field.…”

Role and mechanism of action of butyrate in atherosclerotic diseases: a review

“…Previous studies have shown that butyrate can affect the expression of nine genes in the cholesterol biosynthesis pathway, which affect human metabolism by acting in concert with each other (Alvaro et al 2008). Exercise can reduce fat and prevent obesity, in which butyrate regulates the Sestrin2 (SESN2) / cAMP-Regulated Transcriptional Co-activator 2 (CRTC2) pathway (Yu et al 2019). Furthermore, in apolipoprotein E-deficient mice, butyrate down-regulates cholesterol and delays the development of AS, which mainly manifests as a reduced lesion area of AS (Chen et al 2018;Hoving et al 2018).…”