Human immune responses to environmental changes - A dietary intervention study (ImmoDiet)

• Applicant: Lorenzo Bonaguro, Ph.D.
• Subject Area: Immunology ; Endocrinology, Diabetology, Metabolism
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 513977171

In the proposed study, Human immune responses to environmental changes - A dietary intervention study (ImmoDiet), we aim to bridge the gap in knowledge regarding the effects of dietary intervention on circulating immune cells in humans with an emphasis on individuals at risk to develop NCDs related to overweight, obesity and/or metabolic syndrome. Important research in murine models showed clear evidence for a strong dependency between diet and composition/fitness of the immune system. I, therefore, hypothesize that changes in diet, particularly from Western-style diets to Vegetarian or Nordic diets over a certain period of time will lead to reduced inflammatory tonus or a reduced low-grade chronic inflammation that can be determined by scRNAseq in circulating immune cells. In this respect, highly controlled longitudinal dietary intervention studies are an ideal setting to study the effects induced by dietary changes on the human immune system. Here, I intend to investigate the transcriptional changes at single cell level in peripheral blood in both homeostatic conditions and after ex vivo LPS challenge as a surrogate for immune cell activation. To address the hypothesis, together with colleagues of the department of nutritional and food science, I already conducted a cohort study of male individuals, overweight and with several risk factors for cardiovascular and neurodegenerative diseases and propose here to generate and analyse scRNAseq data. I postulate that the high-dimension, highresolution data derived from scRNAseq will give a picture of unprecedented resolution about the changes that occur within the immune system because of dietary changes. Despite the high dimensionality of the data, the complexity of the composition of each diet will make it difficult to directly build a relationship between single components and the impact on the immune system. I will therefore complement the information derived from the scRNAseq analysis with in vitro experiments where the most likely dietary components will be tested on PBMCs derived from the same participants in the dietary intervention study to link specific components to the observed phenotype. I am confident that this in depth analysis will open new avenues for tailored interventions in individuals at elevated risks for developing NCDs due to chronic low-grade inflammatory immune reactions induced by current dietary habits in our societies.

• DFG Programme: Research Grants