MD/PhD 3 (2018 - 2020) - Regulatory properties of bacterial metabolites on the B cell compartment in allergic diseases

The gut microbiome is increasingly recognized as a major contributor to the regulation of the innate and adaptive immune system. Alongside bacterial antigens the signaling through bacterial metabolites is considered the principal regulatory pathway. Key metabolites, such as Butyric acid (BA), which is produced by commensal gut microbiota in high concentrations (~20-120mM), have been shown to promote regulatory T cells and inhibit proinflammatory cytokine secretion by innate immune cells. Despite their crucial role in mediating defense against pathogens and autoimmunity, modulation of B cell maturation and function by bacterial metabolites has not been investigated sufficiently. Preliminary in vitro experiments show promising effects of butyric acid (BA) on B cell differentiation, possibly to B-regulatory cells. Here, we aim to examine the effects of short-chain fatty acids (incl. BA) and other key metabolites on B cell differentiation, Immunoglobulin-class switching and immunometabolism in a model of allergy.