Feeding Docosahexaenoic Acid and Arachidonic Acid during Suckling and Weaning Contributes to Oral Tolerance Development by Beneficially Modulating the Intestinal Cytokine and Immunoglobulin Levels in an Allergy-Prone Brown Norway Rat Model.

BACKGROUND

Suckling and weaning arachidonic acid (ARA) + docosahexaenoic acid (DHA) supplementation promoted oral tolerance (OT) development in pups, however, the effect of it on the intestine to promote OT development remains unknown.

OBJECTIVE

We aimed to explore the impact of this supplementation on intestinal fatty acid composition, structure, and indicators that are supportive of OT development.

METHODS

Allergy-prone Brown Norway dams were randomly assigned to a control (0% ARA, 0% DHA) or ARA + DHA diet (0.45% ARA, 0.8% DHA) during suckling (0-3 wk). At weaning (3-8 wk), offspring were randomly assigned to a control (0% ARA, 0% DHA) or ARA + DHA diet (0.5% ARA, 0.5% DHA). At 3 wk, offspring in each group received an oral gavage of sucrose or ovalbumin (OVA) solution for five consecutive days. At 7 wk, all offspring received an intraperitoneal OVA injection. At 8 wk, offspring were terminated to evaluate jejunum morphology and measure mucosal food allergy-related secretory immunoglobulin A (sIgA) and cytokines, ileum phospholipid and triglyceride fatty acid compositions, and fecal calprotectin.

RESULTS

Weaning ARA + DHA resulted in a higher percentage of DHA in ileum phospholipids and triglycerides (both P < 0.001), without affecting the percentage of ARA. Despite no lasting effect of suckling ARA + DHA on the DHA content in ileum phospholipids, a programming effect was found on the allergy-related intestinal immune profile [higher concentrations of mucosal IL-2 (P = 0.049) and sIgA (P = 0.033)]. OVA treatment resulted in a lower concentration of mucosal IL-6 (P = 0.026) regardless of dietary interventions. Offspring fed ARA + DHA during suckling and/or weaning had a higher concentration of mucosal transforming growth factor-beta (TGF-β) after OVA treatment but this was not observed in offspring fed control diets during suckling and weaning (P = 0.04).

CONCLUSIONS

Early life dietary ARA + DHA supplementation to allergy-prone rats enhanced the DHA concentration in intestinal phospholipids (weaning period) and increased the mucosal sIgA, IL-2, and TGF-β levels (suckling and weaning period), indicating its ability to create a tolerogenic intestinal environment to support OT development.