Products Cited in Publications Worldwide Impact of gut metabolites and antibiotics on immune responses

Impact of gut metabolites and antibiotics on immune responses

Krimitza, Elisavet

Abstract

Gut microbiota –the assembly of commensal intestinal microorganisms - impacts the host immune system in several ways. Antibiotics -widely used therapeutic agents- are able to modulate the survival and the growth of gut bacteria, as well as the metabolites they produce. Some gut bacteria are already known to affect the T cell development and differentiation. This research thesis investigates the impact that certain antibiotics and metabolites (short chain fatty acids) could have on antigen presentation and T cell activation. Through series of assays evaluating the antigen presentation to CD8+ T cells, this thesis has shown that different metabolites have distinct effects, some are able to boost and others to inhibit the immune responses. We suggest that different metabolites may act through distinct signaling and cytokine transduction pathways. Factors like the concentrations, the timing and the duration of exposure of the APCs to those treatments, together with the type of the metabolite, might hold a role in the activation of different pathways as well. Among the metabolites we tested, propionate was shown to have inhibitory effects on antigen presentation, and the mechanism behind this is probably related to the antigen processing, through upregulation of the IFNα gene. Butyrate might be regulating the expression of the MHC II gene. Antibiotics were found to have no direct impact on T cell activation in vitro or in vivo. Even though the complexity of the gut microbiota impact on the immune system still needs further studies, we overall suggest that fine regulation of the gut metabolites can largely affect the clinical outcomes of multiple therapies.

Keywords

gut microbiome ; immune system ; metabolites ; antigen presentation ; T cell activation

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