Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?

Abstract

As interest in the gut microbiome has grown in recent years, attention has turned to the impact of our diet on our brain. The benefits of a high fiber diet in the colon have been well documented in epidemiological studies, but its potential impact on the brain has largely been understudied. Here, we will review evidence that butyrate, a short-chain fatty acid (SCFA) produced by bacterial fermentation of fiber in the colon, can improve brain health. Butyrate has been extensively studied as a histone deacetylase (HDAC) inhibitor but also functions as a ligand for a subset of G protein-coupled receptors and as an energy metabolite. These diverse modes of action make it well suited for solving the wide array of imbalances frequently encountered in neurological disorders. In this review, we will integrate evidence from the disparate fields of gastroenterology and neuroscience to hypothesize that the metabolism of a high fiber diet in the gut can alter gene expression in the brain to prevent neurodegeneration and promote regeneration.

Keywords: Butyrate; Gut microbiome; Gut-brain axis; High fiber diet; Neuroepigenetics.

Figure 1

Schematic representation of the carbohydrate fermentation pathways that lead to butyrate production in the large intestine. The final enzymes involved in the formation of butyrate are: a. Butyryl CoA:acetate CoA transferase b. Phosphotransbutyrylase/butyrate kinase. Adapted from Pryde et al. 2002 [7].

Figure 2

The proposed mechanisms for the neuroprotective effects of butyrate and the diseases which may benefit from butyrate treatment or a high fiber diet.