Immunogenomic and behavioral consequences of diet and social stress in nonhuman primates (Macaca fascicularis)

Abstract

Aspects of the modern human environment, such as diet and the social environment, are highly variable and are associated with increased morbidity and mortality. One common dietary pattern, the Western diet, is associated with increased markers of inflammation, while the Mediterranean diet, another common human dietary pattern, is linked to anti-inflammatory markers. Similarly, two key aspects of the social environment, social status and social integration, have immunomodulary consequences across taxa. Proinflammatory polarization in the peripheral immune system, therefore, presents a mechanism that may link environmental stress of both sources to suboptimal health. To test this hypothesis, we conducted the first whole diet manipulation to compare Western vs Mediterranean diet patterns in a randomized preclinical trial design. This dissertation describes molecular and behavioral consequences of this dietary manipulation and the social environment, as well as the interaction of the two sources of environmental stress. The first study (Chapter 2) utilizes RNA sequencing data to characterize gene expression in circulating monocytes and establishes genome-wide effects of diet that support the monocyte polarization hypothesis. Furthermore, we found evidence of multiple putative gene regulatory mechanisms, including a strong behavioral response to diet. The second study detailed here (Chapter 3) is an in-depth exploration of the behavioral response to diet. We showed an immediate and persistent behavioral phenotype in which Mediterranean diet-fed monkeys showed reduced isolation and anxiety in a social status-dependent manner. Chapter 4 relates an epigenetic analysis exploring DNA methylation in circulating monocytes. While limited in scope, these data suggested both dietary and social impacts on DNA methylation. When taken together, these studies support the protective role of the Mediterranean diet in immune and behavioral health, a finding with potentially important translational consequences.Chapters 2 and 4 both contained large data files as result tables, which are contained in a data table submitted as supplementary material to this dissertation. Each sheet of the Microsoft Excel document corresponds to a different supplementary table referenced in this dissertation.