The Influence of Sleep and Diet on Human Peripheral Immunity and Chronic Health Conditions

Exposures that disrupt the immune system can affect human health. This study aimed to understand immune variability influenced by exposures from the perspectives of systems biology and multiomics. We recruited 1,001 healthy participants and collected 183 exposures, 1,332 immunophenotypes, whole blood transcriptome, and plasma metabolome. Through exposure-immune wide association analysis, we identified 81 significant signals, with sleep and diet emerging as dominant exposures affecting the immunity. Sleep and diet influence the proportions of innate immune cells and the expression levels of immune cell surface proteins such as CD85j and CD16, respectively. Notably, distinct from the increase in interleukin-1β secretion caused by short-term late sleep onset, long-term late sleep onset triggered chronic inflammation with more metabolic changes. On the basis of the intracorrelation structure of exposure data, composite exposures were constructed and were found to have additional effects on immunophenotypes. Bidirectional mediation analysis revealed that sleep effects on immunity are commonly linked to the transcriptome, whereas dietary influences on immunity are primarily associated with the metabolome. We quantified the mediation effects of exposures, omics, and immunophenotypes and further demonstrated that these effects reflect human immune health or chronic diseases. Our study drew a comprehensive map of "exposure-immunome-omics" and is expected to provide guidance for future health assessment and management.