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Acetate yielding diet protects mice from C. rodentium infection

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Feces

SUBMITTER: patrick gavin

LAB HEAD: Eliana Marino

PROVIDER: PXD008149 | Pride | 2022-02-15

REPOSITORIES: Pride

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An acetate-yielding diet imprints an immune and anti-microbial programme against enteric infection.

Yap Yu Anne YA McLeod Keiran H KH McKenzie Craig I CI Gavin Patrick G PG Davalos-Salas Mercedes M Richards James L JL Moore Robert J RJ Lockett Trevor J TJ Clarke Julie M JM Eng Vik Ven VV Pearson Jaclyn S JS Hamilton-Williams Emma E EE Mackay Charles R CR Mariño Eliana E

Clinical & translational immunology 20210115 1

<h4>Objectives</h4>During gastrointestinal infection, dysbiosis can result in decreased production of microbially derived short-chain fatty acids (SCFAs). In response to the presence of intestinal pathogens, we examined whether an engineered acetate- or butyrate-releasing diet can rectify the deficiency of SCFAs and lead to the resolution of enteric infection.<h4>Methods</h4>We tested whether a high acetate- or butyrate-producing diet (HAMSA or HAMSB, respectively) condition <i>Citrobacter</i> < ...[more]

PMID: 33489123

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