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Microbiota configuration dictates nutritional immune optimization [16s rRNA-seq]

ABSTRACT: Mild or transient dietary restriction (DR) improves many aspects of health and aging. Emerging evidence from us and others has demonstrated that DR also optimizes the development and quality of immune responses. However, the factors and mechanisms involved remain to be elucidated. Here, we demonstrate that DR-induced optimization of immunological memory requires co-operation between memory T cells, the intestinal microbiota, and myeloid cells. Our data indicate that DR enhances the ability of memory T cells to recruit and activate myeloid cells in the context of a secondary infection. Concomitantly, DR promotes expansion of the commensal Bifidobacteria within the large intestine, which supplies the short-chain fatty acid acetate to myeloid cells. Acetate conditioning of the myeloid compartment during DR enhances their capacity to kill pathogens. Enhanced host protection during DR is abolished when Bifidobacteria expansion is prevented, indicating that microbiota configuration and function critically dictates immune responsiveness to this dietary intervention. Altogether, DR induces both memory T cells and the gut microbiota to produce essential, distinct factors that converge on myeloid cells to promote optimal pathogen control. These findings reveal how nutritional cues promote adaptation and co-operation between multiple immune cells and the gut microbiota, which synergize to optimize immunity and protect the collective metaorganism.

ORGANISM(S): feces metagenome

PROVIDER: GSE242696 | GEO | 2023/12/13

REPOSITORIES: GEO

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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.

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Microbiota configuration dictates nutritional immune optimization [16s rRNA-seq]

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