Dataset Information

Butyrate is anti-inflammatory at low and pro-inflammatory at high concentrations

ABSTRACT: Butyrate is a four-carbon short-chain fatty acid produced from microbial fermentation of dietary fibers present at high millimolar concentrations in the colonic lumen.However, in an intact epithelium, macrophages residing in the lamina propria areexposed to only sub-millimolar butyrate concentrations. Current studies show antiinflammatoryproperties of butyrate and suggest that it might have therapeuticapplications in inflammatory bowel disease and colonic cancer. We now show that theeffect of butyrate on human macrophages is strongly concentration dependent. At lowconcentrations (0.1–1 mM), butyrate suppresses LPS-induced production ofproinflammatory cytokines potentially through a combination PPAR-γ signaling andincreased histone acetylation. At high concentrations (10 mM), butyrate promotesproduction of inflammatory cytokines in a mechanism that involves G protein-coupledreceptor GPR109A, the lipid transporter CD36, and the kinase SRC. We propose thatbutyrate is a crucial signaling molecule for intestinal integrity, since intestinaldisruption exposes macrophages to high butyrate concentrations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE272870 | GEO | 2026/06/04

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Background and Aims: Many inflammatory diseases are associated with microbial dysbiosis, which may considerably alter the production of short-chain fatty acids (SCFAs). SCFAs are produced in the large bowel through bacterial fermentation of dietary fiber and play an important role in maintaining gut homeostasis. SCFAs, particularly acetate and butyrate, show beneficial immunomodulatory effects contributing to the prevention of inflammatory and allergic reactions. Thus, reduced production of SCFAs may impact on the mucosal immune responses critical to fighting pathogens. This study aims to determine the influence of SCFAs on a murine model of colonic bacterial infection. Methods: In the present study, we used acetate- (HAMSA) or butyrate- (HAMSB) yielding diets to deliver high concentrations of individual SCFAs to the large bowel of mice infected with C. rodentium. We assessed the effects of these SCFAs on clinical burden and gut pathogenicity in correlation with changes in bacteria growth, fecal microbiota composition, function and changes in the immunological profile. Results: Here we show in vitro that acetate and butyrate directly inhibited growth of the attaching and effacing (A/E) pathogen C. rodentium in a bacteriostatic manner. This correlated with reduced expression of Tir, a gene responsible for bacterial adherence and pathogenicity. Interestingly, HAMSA-fed mice presented reduced clinical scores during C. rodentium infection associated with high concentrations of fecal acetate. This was linked with compositional and functional changes in the microbiota when examining 16s sequencing and proteomics analysis. The HAMSA mediated is protection involved increased expression IL-22 and Muc-2 in the colon and increased numbers of CD8αα+ TCRγδ T cells in the colonic epithelium. These effects were dependent on GPR43, a metabolite-sensing GPCR that binds acetate. Conclusions: We established a promising new approach to moderate bacterial gut infections by manipulating the gut microbiota and mucosal immune tolerance through diets that yield the SCFA acetate.

Dataset Information

Butyrate is anti-inflammatory at low and pro-inflammatory at high concentrations

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets