Abstract

The beneficial effect of short-chain fatty acids (SCFAs) on host health has been well recognized based on the booming knowledge from gut microbiome research. The role of SCFA in influencing psychological function is highlighted in recent years but has not been fully elucidated. In this study, the SCFA-acylated starches were used to accomplish a sizeable intestine-targeted release of the SCFAs, and the neurobehavioral, immunological, and microbial effects were further investigated. Acetylated-, butylated-, and isobutylated-starch could attenuate the depression-like behaviors and excessive corticosterone production in chronically stressed mice. Butylated- starch significantly reduced the colonic permeability via increasing the tight junction proteins (including ZO-1, Claudin, and Occludin) gene expression and reduced the level of the inflammatory cytokines (including IL-1β and IL-6). The butylated starch’s neurological and immunological benefits may be derived from the gut microbiome modifications, including normalizing the abundance of certain beneficial microbes (Odoribacter and Oscillibacter) and metabolomic pathways (Tryptophan synthesis and Inositol degradation). The present findings further validate the brain-beneficial effect of butyrate and offer novel guidance for developing novel food or dietary supplements for improving mental health.

Highlights

  • Short-chain fatty acids (SCFAs) are the primary products of gut microbial fermentation from the undigested dietary fibers [1]

  • The stressed mice showed a significantly reduced time spent in the center zone of the open field, but no SCFA-acylated starch reversed this abnormality (Figure S1)

  • The hyperactivity of the hypothalamuspituitary-adrenal axis was observed in the stressed mice, as reflected by the significantly increased serum corticosterone level (P=0.002; Figure 1E)

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Summary

Introduction

Short-chain fatty acids (SCFAs) are the primary products of gut microbial fermentation from the undigested dietary fibers [1]. Propionate, and butyrate (or isobutyrate) are the three major SCFAs [2]. The regular communication between SCFAs and hosts participates in multiple physiological processes, including nutrients metabolism and immune system function [3]. These SCFAs have been demonstrated to affect the host through multiple mechanisms: (a) SCFAs are Butylated Starch, Brain, and Immunity energy sources for gastrointestinal mucosal cells. Butyrate is the primary energy source for colonocytes [4]. (c) SCFAs could act as the histone deacetylases (HDACs) and normalize the gene expression involving cell proliferation and anti-inflammatory process [6] The activation of GPR43 and GPR41 via SCFAs promotes the secretion of various hormones involving blood glucose maintenance, such as glucagon-like peptide-1 (GLP-1) and peptide tyrosine (PYY) [5, 6]. (c) SCFAs could act as the histone deacetylases (HDACs) and normalize the gene expression involving cell proliferation and anti-inflammatory process [6]

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