Feeding a Maternal Diet Enriched in Docosahexaenoic Acid to Lactating Dams Improves the Ex Vivo Tolerance Response to Egg Protein in Suckled Pups

Abstract

An important T cell mediated process that occurs early in life is the development of oral tolerance (OT). Food allergies are believed to be the result of a failure to develop OT to a dietary antigen. The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA) while containing adequate amounts of arachidonic acid (AA) during the suckling period on the development of the immune system and OT in offspring.Sprague‐Dawley dams were randomized to one of the two nutritionally adequate experimental diets 24–48h prior to parturition: control diet (N=12, 0.4% AA and 0% DHA of total fatty acids) or high DHA diet (N=8, 0.4% AA and 0.9% DHA of total fatty acids). Diets were fed to dams ad libitum throughout the suckling period (21 days) and matched for macronutrient, micronutrient and fatty acid content differing only in the composition of omega‐3. At 14‐days pups from each dam were randomly assigned to a mucosal OT challenge for 5 days: placebo (sucrose) or ovalbumin (OVA). At 3 weeks, pups were euthanized and immune cell phenotypes and cytokine production by mitogen‐ (Concanavalin A (ConA), lipopolysaccharide (LPS)) or OVA‐stimulated splenocytes were measured by direct immunofluorescence assay and ELISA, respectively.Feeding dams a high DHA diet increased the proportion of DHA and AA found in breast milk vs. the control diet (both P<0.01). Regardless of the OT challenge, feeding a high DHA diet led to a higher production of interferon‐γ by splenocytes stimulated with ConA and a higher production of interleukin (IL)‐6, IL‐10 and tumor necrosis factor‐α after LPS stimulation (all P<0.05). OVA‐stimulated splenocytes from suckled pups fed the high DHA diet produced significantly more IL‐10 and less transforming growth factor‐β compared to the control diet (both P<0.02), suggestive of better OT. The OT challenge with OVA resulted in a lower production of IL‐6 by LPS‐stimulated splenocytes and led to a higher proportion of cytotoxic T cells expressing CD28 and total cells expressing CD27 (all P<0.02) compared to non‐tolerized pups.Our results suggest that feeding a maternal diet enriched in DHA during the suckling period improves the ability of splenocytes to respond ex vivo to mitogens and the tolerance response to a dietary antigen. Irrespective of the suckling diet, pups who had been orally tolerized to OVA had a lower response to a bacterial antigen despite the presence of more activated T cells and memory immune cells.Support or Funding InformationSupported from the Natural Sciences and Engineering Research Council of Canada. CR holds a scholarship from Canadian Institutes for Health Research and Fonds de recherche en santé du Québec.