DIYUFOOD

From diet to a healthy immune system: understanding biological food paths to oppose metabolic syndromes and infectious diseases

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Abstract

A healthy, balanced diet plays a crucial role in maintaining metabolic health and supporting the immune system. Obesity has been linked to various metabolic syndromes, such as dyslipidemia, hyperglycemia, and fatty liver. The presence of hyperglycemia and lipid accumulation can stimulate lipid oxidation, resulting in the overproduction of cytokines, hyperactivation of the complement system, and activation of the coagulation system. These immune responses can serve as triggers for severe infections, including COVID-19, and other infectious diseases. In our current project, known as the DIYUFOOD project, we aim to leverage extensive multi-omics and clinical data collected from four population-based cohort studies conducted in Israel, the Netherlands, the UK, and China. These studies encompass diverse ethnic backgrounds, dietary patterns, and socioeconomic statuses. By employing mediation analysis in observational studies and Mendelian randomization (MR) analysis, which uses genetic variants as instrumental variables for causal inference, we seek to unravel the causal pathways involved.

Initially, we will explore the potential associations between dietary patterns and immune response, as well as identify potential metabolic mediators that can explain the observed connections between diet and immune response. This analysis will be conducted in the four observational studies. Next, we will investigate the mediating roles of gut microbial composition in the associations between dietary patterns and immune response. Once specific species of microorganisms are identified in this second step, we will further examine the roles of circulating metabolites in mediating the associations between gut microbial composition and immune response. It is important to note that the gut microbiota produces an incredibly diverse range of metabolites. Finally, for all the associations observed from step 1 to step 3, including those between metabolic syndromes, gut-microbiota derived metabolites, and immune response, we will utilize MR studies to further validate the causal relationships. Moreover, we will expand our analysis to explore the associations between metabolic syndromes, gut microbiota-derived metabolites, and the severity of COVID-19 as well as long-COVID. This will be accomplished through the utilization of multivariable MR analysis, which takes into account multiple variables simultaneously.

The biological "food path" from dietary intake to immune response and subsequent disease outcomes is highly complex. Our project aims to provide a deeper understanding of the underlying causal pathways, as this knowledge is essential for developing effective food solutions to mitigate disease risks.