Abstract
Background: Dietary long chain polyunsaturated fatty acids (LCPUFA) such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) play an important role in the development of the infant immune system. The role of LCPUFA in the T helper type 2 (Th2) biased immune system is unknown. We aimed to understand the effect of feeding LCPUFA during suckling and post-weaning on immune system development in Th2 bias Brown Norway rat offspring.Methods: Brown Norway dams were randomly assigned to nutritionally adequate maternal diet throughout the suckling period (0–3 weeks), namely, control diet (0% ARA, 0% DHA; n= 8) or ARA + DHA (0.45% ARA, 0.8% DHA; n = 10). At 3 weeks, offspring from each maternal diet group were randomized to either a control (0% ARA, 0% DHA; n = 19) or ARA+DHA post-weaning (0.5% ARA, 0.5% DHA; n = 18) diet. At 8 weeks, offspring were killed, and tissues were collected for immune cell function and fatty acid composition analyses.Results: ARA + DHA maternal diet resulted in higher (p < 0.05) DHA composition in breast milk (4×) without changing ARA levels. This resulted in more mature adaptive immune cells in spleen [T regulatory (Treg) cells and B cells], mesenteric lymph nodes (MLN, lower CD45RA+), and Peyer's patches (PP; higher IgG+, B cells) in the ARA+DHA group offspring at 8 weeks. ARA+DHA post-weaning diet (3–8 weeks) resulted in 2 × higher DHA in splenocyte phospholipids compared to control. This also resulted in higher Th1 cytokines, ~50% higher TNF-α and IFNγ, by PMAi stimulated splenocytes ex vivo, with no differences in Th2 cytokines (IL-4, IL-13, and IL-10) compared to controls.Conclusion: Feeding dams a diet higher in DHA during the suckling period resulted in adaptive immune cell maturation in offspring at 8 weeks. Providing ARA and DHA during the post-weaning period in a Th2 biased Brown Norway offspring model may support Th1 biased immune response development, which could be associated with a lower risk of developing atopic diseases.
Highlights
Docosahexaenoic acid (DHA), an omega-3 (n−3/ω-3) long chain polyunsaturated fatty acid (LCPUFA), and arachidonic acid (ARA), an n−6 LCPUFA are essential fatty acids needed for infant neural and vision development [1, 2]
This resulted in more mature adaptive immune cells in spleen [T regulatory (Treg) cells and B cells], mesenteric lymph nodes (MLN, lower CD45RA+), and Peyer’s patches (PP; higher IgG+, B cells) in the ARA+DHA group offspring at 8 weeks
ALA, α-linolenic acid; LA, linoleic acid; ARA, arachidonic acid; DHA, docosahexaenoic acid; PUFA, polyunsaturated fatty acid; monounsaturated fatty acids (MUFA), monounsaturated fatty acid; SFA, saturated fatty acid. bSome fatty acids that were traced were not presented as they were very small or not relevant, this may lead to a mismatch in total proportions of fatty acids such as total SFA, PUFA, MUFA, n−6, and n−3. cIndicates p-value for a T-test for the difference between maternal diets. dIndicates p-value for a T-test for the difference between post-weaning diets
Summary
Docosahexaenoic acid (DHA), an omega-3 (n−3/ω-3) long chain polyunsaturated fatty acid (LCPUFA), and arachidonic acid (ARA), an n−6 LCPUFA are essential fatty acids needed for infant neural and vision development [1, 2]. Their role in the development of the immune system, in those at risk for atopic conditions due to T helper type-2 (Th2) dominant immunity, has been sparsely studied. Studies have shown beneficial effects of DHA in populations predisposed to developing conditions associated with Th2 dominance [3, 4] These studies were often conducted using a diet containing no ARA or a very high level of DHA. We aimed to understand the effect of feeding LCPUFA during suckling and post-weaning on immune system development in Th2 bias Brown Norway rat offspring
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