Abstract
Allergic diseases have become a major health problem, partly due to reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid ratio. Prenatal exposures have been reported to influence allergy development, possibly induced via changes in maternal immune regulation. In a randomized double-blind placebo-controlled multicenter allergy prevention trial (PROOM-3), pregnant women were recruited at gestational week 20, and randomized to four study groups, one receiving both L. reuteri oil drops and ω-3 PUFA capsules (n = 22), the second receiving ω-3 PUFA supplementation and placebo regarding L. reuteri (n = 21), the third receiving L. reuteri and placebo regarding ω-3 PUFA (n = 22) and the fourth group receiving placebo capsules and placebo oil drops (n = 23). In this substudy, supplemental and pregnancy-related effects on maternal peripheral immune cell populations during pregnancy were assessed by flow cytometry immune phenotyping at gestational week 20, 32 and 4 days after delivery. The numbers of activated and regulatory T (Treg) cells (CD45RA− Foxp3++/CD45RA+Foxp3+) were reduced after delivery, with the lowest count in the L. reuteri supplemented group compared with the placebo group 4 days after delivery, while the ω-3 PUFA group did not differ from the placebo group. Several treatment-independent changes were observed during and after pregnancy in lymphocytes (CD4+/8+/19+/56+/45RA+/−), CD14+16+/− monocytes, and in subpopulations of T helper cells (Th) CD4+CD45RA−Tbet+ (Th1) and CD4+CD45RA−RORC+ (Th17) cells. In conclusion, probiotic supplementation to the mother during the second half of pregnancy resulted in immunomodulatory effects among activated and resting Treg cells. Furthermore, several systemic immune modifying effects of pregnancy were observed.
Highlights
Allergic diseases have become a major health problem, partly due to reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid ratio
A significant difference was noted for T regulatory cells (Tregs) cells when considering all groups including placebo and groups supplemented with ω-3 and probiotics during pregnancy
Comparing the placebo + placebo group with the treatment groups (Mann–Whitney U test and Bonferroni correction) at 4 days after delivery revealed that the L. reuteri group had significantly lower numbers of resting Treg cells ( CD4+CD45RA+Foxp3+, adjusted p = 0.036, Fig. 1A) as well of activated Treg cells (CD4+CD45RA−Foxp3+, adjusted p = 0.021, Fig. 1B)
Summary
Allergic diseases have become a major health problem, partly due to reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid ratio. A reduced amount and diversity of microbial encounters and a decreased dietary ω-3-/ω-6 long-chain polyunsaturated fatty acid ratio could be one of the key factors in the development of a deviated immune maturation[7,8]. Based on these hypotheses, both probiotics and ω-3 fatty acids have been used in infant allergy prevention trials[9,10,11,12,13]. More detailed studies on how systemic immunity is modulated during pregnancy are required since existing studies show conflicting results including monocytes, NK-cells and T- helper cell subsets regarding changes in peripheral immune cell p opulations[30,34,35,36]
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