Butyrate upregulates endogenous host defense peptides to enhance disease resistance in piglets via histone deacetylase inhibition

Abstract

Butyrate has been used to treat different inflammatory disease with positive outcomes, the mechanisms by which butyrate exerts its anti-inflammatory effects remain largely undefined. Here we proposed a new mechanism that butyrate manipulate endogenous host defense peptides (HDPs) which contributes to the elimination of Escherichia coli O157:H7, and thus affects the alleviation of inflammation. An experiment in piglets treated with butyrate (0.2% of diets) 2 days before E. coli O157:H7 challenge was designed to investigate porcine HDP expression, inflammation and E. coli O157:H7 load in feces. The mechanisms underlying butyrate-induced HDP gene expression and the antibacterial activity and bacterial clearance of macrophage 3D4/2 cells in vitro were examined. Butyrate treatment (i) alleviated the clinical symptoms of E. coli O157:H7-induced hemolytic uremic syndrome (HUS) and the severity of intestinal inflammation; (ii) reduced the E. coli O157:H7 load in feces; (iii) significantly upregulated multiple, but not all, HDPs in vitro and in vivo via histone deacetylase (HDAC) inhibition; and (iv) enhanced the antibacterial activity and bacterial clearance of 3D4/2 cells. Our findings indicate that butyrate enhances disease resistance, promotes the clearance of E. coli O157:H7, and alleviates the clinical symptoms of HUS and inflammation, partially, by affecting HDP expression via HDAC inhibition.

Inside Out: HIV, the Gut Microbiome, and the Mucosal Immune System

“…Most interventions studied to date, in several different disease settings, have focused on either directly repopulating the gut with beneficial commensals (probiotics or direct fecal transplant) or encouraging the growth of beneficial commensals with intake of substrate for their growth (prebiotics). Other interventions involve repletion of important biomolecules such as introducing intracolonic butyrate to ameliorate autoimmune disease (118) or active infection (in piglets) (119). Furthermore, still other preclinical study interventions are investigating directed exercise regimens to alter the gut microbiota for health benefit (123).…”

“…Butyrate not only nourishes colonocytes but also stimulates production of mucin, enhancing gut mucosal barrier integrity. Xiong et al (119) showed in 2016 that butyrate directly upregulated host defense peptides in piglet gut epithelial cells and helped ameliorate the pathogenic consequences of E. coli 0157:H7 infection. Additionally, butyrate reportedly regulates and expands the colonic Treg population, promoting an antiinflammatory phenotype (120,121).…”

The Control of Intestinal Inflammation: A Major Objective in the Research of Probiotic Strains as Alternatives to Antibiotic Growth Promoters in Poultry

“…It has been observed that IL-18, also induced by the presence of SCFAs, has a reparative and maintenance effect on the epithelial barrier [45]. Moreover, SCFAs are capable of recruiting Treg cells (increase in tolerance) and inducing the expression of host defense peptides (HDP) via histone deacetylase inhibition, enhancing the antibacterial activity and bacterial clearance of macrophages [46,47].…”

Dietary ALoe vera gel and Microbiota Interactions: Influence of Butyrate and Insulin Sensitivity

“…HDAC3 activity/ HDAC3 mRNA levels positively correlated to pro-inflammation, poor glycemic control, and insulin resistance. Xiong H group [22] proposed a new mechanism that butyrate manipulates endogenous host defense peptide (HDP) which contributes to the elimination of Escherichia coli O157:H7, and thus affects the alleviation of inflammation. The findings indicate that butyrate enhances disease resistance, promotes the clearance of E.coli O157:H7, and alleviates the clinical symptoms of E.coli O157:H7-induced hemolytic uremic syndrome and inflammation, partially, by affecting host defense peptide expression via HDAC inhibition.…”