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

Autor: Mercedes Davalos-Salas, Patrick G. Gavin, Yu Anne Yap, Jaclyn S. Pearson, Charles R. Mackay, Robert J. Moore, James L. Richards, Vik Ven Eng, Eliana Mariño, Julie M. Clarke, Trevor Lockett, Keiran H. McLeod, Emma E. Hamilton-Williams, Craig R. M. McKenzie
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Clinical & Translational Immunology
ISSN: 2050-0068
Popis: Objectives 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. Methods We tested whether a high acetate‐ or butyrate‐producing diet (HAMSA or HAMSB, respectively) condition Citrobacter rodentium infection in mice and assess its impact on host‐microbiota interactions. We analysed the adaptive and innate immune responses, changes in gut microbiome function, epithelial barrier function and the molecular mechanism via metabolite sensing G protein‐coupled receptor 43 (GPR43) and IL‐22 expression. Results HAMSA diet rectified the deficiency in acetate production and protected against enteric infection. Increased SCFAs affect the expression of pathogen virulence genes. HAMSA diet promoted compositional and functional changes in the gut microbiota during infection similar to healthy microbiota from non‐infected mice. Bacterial changes were evidenced by the production of proteins involved in acetate utilisation, starch and sugar degradation, amino acid biosynthesis, carbohydrate transport and metabolism. HAMSA diet also induced changes in host proteins critical in glycolysis, wound healing such as GPX1 and epithelial architecture such as EZR1 and PFN1. Dietary acetate assisted in rapid epithelial repair, as shown by increased colonic Muc‐2, Il‐22, and anti‐microbial peptides. We found that acetate increased numbers of colonic IL‐22 producing TCRαβ+CD8αβ+ and TCRγδ+CD8αα+ intraepithelial lymphocytes expressing GPR43. Conclusion HAMSA diet may be an effective therapeutic approach for fighting inflammation and enteric infections and offer a safe alternative that may impact on human health.
Specialised diets that produce high concentrations of acetate are a novel approach to protect against intestinal bacterial infections. We show that modified starches yielding short‐chain fatty acids delivered during gut infection mediate functional microbiota changes and intraepithelial lymphocyte expansion and activation via GPR43 central to aid in preserving epithelial barrier integrity and bacterial clearance.
Databáze: OpenAIRE
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