Abstract

The “Western diet” is characterized by increased intake of saturated and omega-6 (n−6) fatty acids with a relative reduction in omega-3 (n−3) consumption. These fatty acids can directly and indirectly modulate the gut microbiome, resulting in altered host immunity. Omega-3 fatty acids can also directly modulate immunity through alterations in the phospholipid membranes of immune cells, inhibition of n−6 induced inflammation, down-regulation of inflammatory transcription factors, and by serving as pre-cursors to anti-inflammatory lipid mediators such as resolvins and protectins. We have previously shown that consumption by breeder mice of diets high in saturated and n−6 fatty acids have inflammatory and immune-modulating effects on offspring that are at least partially driven by vertical transmission of altered gut microbiota. To determine if parental diets high in n−3 fatty acids could also affect offspring microbiome and immunity, we fed breeding mice an n−3-rich diet with 40% calories from fat and measured immune outcomes in their offspring. We found offspring from mice fed diets high in n−3 had altered gut microbiomes and modestly enhanced anti-inflammatory IL-10 from both colonic and splenic tissue. Omega-3 pups were protected during peanut oral allergy challenge with small but measurable alterations in peanut-related serologies. However, n−3 pups displayed a tendency toward worsened responses during E. coli sepsis and had significantly worse outcomes during Staphylococcus aureus skin infection. Our results indicate excess parental n−3 fatty acid intake alters microbiome and immune response in offspring.

Highlights

  • The modern ‘Western diet’, characterized by increased intake of saturated dietary fat and refined sugar, is correlated with inflammatory and immune-mediated diseases [1]

  • Compared to offspring of mice fed a standard diet, we show that offspring of mice fed a high n23 polyunsaturated fatty acids (PUFA) diet had an altered microbiome and decreased inflammatory responses in models of allergy and infection

  • In our previously published study, pups from breeders fed the Western diet had dramatic shifts in their gut microbiome compared to pups from mice fed a standard low fat diet [13]

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Summary

Introduction

The modern ‘Western diet’, characterized by increased intake of saturated dietary fat and refined sugar, is correlated with inflammatory and immune-mediated diseases [1]. PUFA influence the inflammatory response, with n26 PUFA generally associated with pro-inflammatory effects [3,4] and n23 PUFA generally associated with antiinflammatory effects [3,4,5]. This raises the possibility of dietary supplementation with n23 PUFA, such as in fish oil, as an effective treatment for inflammatory diseases [3,4,6,7]. There is evidence that n23 PUFA are important during development, and that maternal intake during pregnancy protects against the development of allergic and inflammatory disease in infants and children [2] and improves pregnancy outcomes [8]

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