Atopic dermatitis prevention in children following maternal probiotic supplementation does not appear to be mediated by breast milk TSLP or TGF-β

Abstract

BackgroundThe Probiotics in Prevention of Allergy among Children in Trondheim (ProPACT) study, a randomised, placebo controlled trial, demonstrated that maternal supplementation with probiotic milk reduced the incidence of atopic dermatitis (AD) in infancy. The mechanisms behind this effect are incompletely understood and breast milk cytokines have been postulated as possible mediating factors. In this study we aimed to assess whether breast milk TLSP and TGF-β are affected by a maternal probiotic supplementation regime, and their contribution to the preventive effect of this regime on AD in the offspring.MethodsTSLP and TGF-β isoforms (TGF-β1, TGF-β2 and TGF-β3) were measured using ELISA and multiplex assays, respectively, in breast milk samples collected at 10 days and 3 months postpartum from women participating in the ProPACT trial (n = 259). The natural indirect and direct effects of maternal probiotics on AD, due to changes in breast milk cytokines, were estimated using causal mediation techniques.ResultsProbiotic supplementation tend to lead to high levels of breast milk TSLP at 10 days postpartum (p = 0.062), but this change did not contribute to the prevention of AD according to the mediation analysis. Probiotics had no apparent effect on TSLP at 3 months or TGF-βs at either time points. Thus, these are unlikely to be mediators of the effect of maternal probiotics on AD in offspring.ConclusionsWhilst maternal probiotic supplementation resulted in higher breast milk concentrations of TLSP at 10 days postpartum, this does not appear to be a mechanism for prevention of AD by maternal probiotics.Trial registration The original trial protocol is registered in ClinicalTrials.gov (identifier NCT00159523)

Transforming growth factor beta in human milk and allergic outcomes in children: A systematic review

“…However, the analyses of interventional studies were undertaken within the studies without assessing the association between intervention and allergic outcomes in children. Ten studies measured TGF‐β1, two investigated TGF‐β2, 6 looked at both TGF‐β1 and TGF‐β2 and two studies assessed all three TGF‐β isoforms …”

“…Colostrum was collected within 0‐4 days, transitional milk (TM) 5‐14 days and mature milk (MM) between 15 days and 6 months post‐partum . Eight cohorts measured TGF‐β levels in paired colostrum and MM samples.…”

“…Eight cohorts measured TGF‐β levels in paired colostrum and MM samples. Of the remaining cohorts, three assessed TGF‐β levels in colostrum; one in TM; two in TM and MM and seven in MM …”

“…Sixteen of 21 studies used enzyme‐linked immunosorbent assay (ELISA) to quantify TGF‐β levels in HM. Other techniques included: immunoassay, multiplex assay, custom‐made multiplex assays, electro‐chemiluminescence and quantikine immunoassay . There was a considerable heterogeneity in reported TGF‐β concentrations, which made quantitative synthesis (meta‐analysis) not possible.…”

“…Some studies reported “trends,” not supported by the statistical analysis results ( P values > 0.05) and only three studies accounted for multiple comparisons. Half of the studies adjusted for potential confounders, including age, delivery mode, atopic status, length of breastfeeding, use of probiotics, site of collection, HM collection time, total storage time until analysis, introduction of food during the first year of life, paternal history of allergic diseases and presence of older siblings (Table ).…”