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.