Dataset Information

The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition.

ABSTRACT: Given the trillions of microbes that inhabit the mammalian intestines, the host immune system must constantly maintain a balance between tolerance to commensals and immunity against pathogens to avoid unnecessary immune responses against otherwise harmless bacteria. Misregulated responses can lead to inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. The mechanisms by which the immune system maintains this critical balance remain largely undefined. Here, we demonstrate that the short-chain fatty acid n-butyrate, which is secreted in high amounts by commensal bacteria, can modulate the function of intestinal macrophages, the most abundant immune cell type in the lamina propria. Treatment of macrophages with n-butyrate led to the down-regulation of lipopolysaccharide-induced proinflammatory mediators, including nitric oxide, IL-6, and IL-12, but did not affect levels of TNF-? or MCP-1. These effects were independent of toll-like receptor signaling and activation of G-protein-coupled receptors, two pathways that could be affected by short-chain fatty acids. In this study, we provide several lines of evidence that suggest that these effects are due to the inhibition of histone deacetylases by n-butyrate. These findings elucidate a pathway in which the host may maintain tolerance to intestinal microbiota by rendering lamina propria macrophages hyporesponsive to commensal bacteria through the down-regulation of proinflammatory effectors.

SUBMITTER: Chang PV

PROVIDER: S-EPMC3926023 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition.

Chang Pamela V PV Hao Liming L Offermanns Stefan S Medzhitov Ruslan R

Proceedings of the National Academy of Sciences of the United States of America 20140103 6

Given the trillions of microbes that inhabit the mammalian intestines, the host immune system must constantly maintain a balance between tolerance to commensals and immunity against pathogens to avoid unnecessary immune responses against otherwise harmless bacteria. Misregulated responses can lead to inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. The mechanisms by which the immune system maintains this critical balance remain largely undefined. Here, we demonstrate th ...[more]

PMID: 24390544

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Project description:This study investigated the effects of dietary sodium butyrate (SB) supplementation, provided as a specially coated product, on growth performance, intestinal development, morphological structure and function in broilers. In total, 720 one-day-old Arbor Acres male broilers were randomly allocated into six treatment groups with six replicates each and then fed basal diets (control) supplemented with 0, 200, 400, 800 or 1000 mg/kg of SB or with antibiotics (100 mg/kg aureomycin and 20 mg/kg colistin sulfate). The growth trial lasted for 42 days. No differences (P>0.05) in growth performance were detected between groups during the grower period (1-21 d) or over the total (1-42 d) trial period, whereas the addition of SB improved the intestinal structure by stimulating (P<0.05) goblet cells on jejunal and ileal villi accompanied by a trend towards increased (Pdiets<0.10) ileal villus height. In addition, more inerratic leaf-shaped villi and mucus secretion and significantly fewer erosions were demonstrated by scanning electron microscopy. Apart from decreased (P<0.05) malondialdehyde (MDA) in the ileal mucosa at 21 d of age, supplemental SB at higher doses (800 mg/kg) led to greater (P<0.05) total antioxidant capacity and depressed (P<0.05) MDA concentrations in the jejunal mucosa. Birds fed with 400 mg/kg and 800 mg/kg SB had higher (P<0.05) acetic acid concentrations at 42 d and higher butyric acid at 21 d in the jejunum chyme. Morever, chicks fed SB diet were found to have higher concentrations of butyric acid (P<0.05) in the ileal chyme. SB additions at 400 mg/kg displayed higher Firmicutes and Proteobacteria levels, while a higher (P<0.05) relative abundance of Bacteroidetes was observed at 800 mg/kg. Furthermore, we found a striking decrease in Enterobacteriaceae and increases in Lachnospiraceae and Rikenellaceae in the cecal lumen of birds fed 800 mg/kg SB as well as a higher proportion of Ruminococcaceae and a noticeable reduction (P<0.05) of Lactobacillaceae in birds treated with 400 mg/kg SB. Taken together, our results support the importance of SB in improving the intestinal development, morphological structure and biological functions of broilers through modulation of the microbial community, which seems to be optimized for gut health at higher doses (800 mg/kg) of SB.

Dataset Information

The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition.

Publications

The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition.

Similar Datasets

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