Abstract

Unbalanced dietary habits and gut dysmotility are causative factors in metabolic and functional gut disorders, including obesity, diabetes, and constipation. Reduction in luminal butyrate synthesis is known to be associated with gut dysbioses, and studies have suggested that restoring butyrate formation in the colon may improve gut health. In contrast, shifts in different types of gut microbiota may inhibit luminal butyrate synthesis, requiring different treatments to restore colonic bacterial butyrate synthesis. We investigated the influence of high-fat diets (HFD) and low-fiber diets (LFD), and loperamide (LPM) administration, on key bacteria and genes involved in reduction of butyrate synthesis in mice. MiSeq-based microbiota analysis and HiSeq-based differential gene analysis indicated that different types of bacteria and genes were involved in butyrate metabolism in each treatment. Dietary modulation depleted butyrate kinase and phosphate butyryl transferase by decreasing members of the Bacteroidales and Parabacteroides. The HFD also depleted genes involved in succinate synthesis by decreasing Lactobacillus. The LFD and LPM treatments depleted genes involved in crotonoyl-CoA synthesis by decreasing Roseburia and Oscilllibacter. Taken together, our results suggest that different types of bacteria and genes were involved in gut dysbiosis, and that selected treatments may be needed depending on the cause of gut dysfunction.

Highlights

  • Butyrate is a bioactive compound that inhibits histone deacetylase (HDAC)

  • We investigated the bacteria and genes involved in butyrate synthesis using a mouse model of gut dysbiosis

  • 1 show that high-fat diets (HFD), low-fiber diets (LFD), and amount amount of mucinof inmucin goblet in cells cells

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Summary

Introduction

Butyrate is a bioactive compound that inhibits histone deacetylase (HDAC). Inhibition of HDAC has been studied in mammalian cells, and inhibits proliferation, induction of differentiation, and induction/repression of gene expression. Inhibition of HDAC activity affects the expression of only ~2% of mammalian genes [1]. Butyrate is known to activate G-protein-coupled receptors (GPCR), by which it regulates diverse body functions. Butyrate has antitumor activity by activating GPR43 [2]. Recent gut microbiome studies have revealed that butyrate serves as an energy source to gut epithelial cells. Donohoe et al [3] reported that gut microbiota influences the

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