Abstract
Abstract Mechanisms underlying modern increases in prevalence of human inflammatory diseases remain unclear. The hygiene hypothesis postulates that decreased microbial exposure has, at least in part, driven this immune dysregulation. However, dietary fatty acids may also influence immunity, partially through modulation of host responses to microbes. To test the hypothesis that parental dietary fat consumption during gestation and lactation influences offspring immunity, we compared pups of mice fed either a Western diet fatty acid profile or a standard low fat diet. We found that pups from Western diet breeders were not obese or diabetic, but still had worse outcomes in models of infection, autoimmunity, and allergic sensitization. They had heightened colonic inflammatory responses, with increased circulating bacterial lipopolysaccharide (LPS) and muted systemic LPS responsiveness. These deleterious impacts of the Western diet were associated with alterations of the offspring gut microbiome. These results indicate that parental fat consumption can leave a “lard legacy” impacting offspring immunity.
Published Version
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