AbstractWestern diet consumption is associated with inflammation, cardiometabolic disease, and mortality in humans, while Mediterranean diet consumption confers protective effects. One likely pathway for this association is through environmentally induced changes in monocyte function, yet the underlying mechanisms remain elusive. We conducted the first randomized, long-term diet manipulation in a non-human primate model to determine whether Western- or Mediterranean-like diets alter monocyte polarization and health. Monocyte gene expression profiles differed markedly between the two diet groups, with significant differences in over 40% of expressed genes. The Western diet induced a more proinflammatory monocyte phenotype overall and upregulated specific monocyte polarization genes. Diet also disrupted the coexpression of numerous gene pairs, including small RNAs and transcription factors associated with metabolism and adiposity in humans. Diet altered affiliative and anxiety-associated behaviors and mediation analysis showed that the diet-altered behaviors contributed significantly (∼50% of the effect of diet on gene expression) to 25% of the differentially expressed genes, suggesting that diet effects on central mechanisms also modulate monocyte gene expression. Together, these results identify both behavioral and molecular mechanisms underlying the health benefits of a Mediterranean diet regimen.Significance StatementSome of our largest public health burdens are driven by dietary changes associated with industrialization, but we still know very little about the molecular mechanisms underlying this link. Characteristic “Western diets” have been associated with increased risk for diseases related to chronic inflammation, while Mediterranean diets have anti-inflammatory benefits. Here, we identify causal effects of diet on inflammatory gene expression where consumption of the Mediterranean diet reduced inflammatory gene expression in monocytes. Additionally, our diet manipulation induced behavioral changes associated with anxiety and social integration, where Mediterranean-fed animals exhibited more positive affiliative behaviors and reduced anxiety. These behaviors were associated with 25% of the diet-affected genes, suggesting an important behavioral route through which diet can impact immune function.
Inflammatory gene expression profiles in Crohn's disease and ulcerative colitis: A comparative analysis using a reverse transcriptase multiplex ligation-dependent probe amplification protocol
