Infant consumption of microRNA miR-375 in human milk lipids is associated with protection from atopy

Background: Human milk is thought to reduce infant atopy risk. The biologic mechanism for this protective effect is not fully understood. Objectives: We tested the hypothesis that infant consumption of 4 microRNAs (miR-146b-5p, miR-148b-3p, miR-21–5p, and miR-375–3p) in human milk would be associated with reduced atopy risk. Methods: The Breast Milk Influence of the Microtranscriptome Profile on Atopy in Children over Time (IMPACT) study involved a cohort of mother-infant dyads who planned to breastfeed beyond 4 mo. Infant consumption of the 4 human milk microRNAs (miRNAs) in the first 6 mo was calculated as the product of milk miRNA concentration and the number of human milk feeds, across 3 lactation stages: early milk (0–4 wk), transitional milk (4–16 wk), and mature milk (16–24 wk). The primary outcome was infant atopy in the first year, defined as atopic dermatitis (AD), food allergies, or wheezing. The final analysis included 432 human milk samples and 7824 wk of longitudinal health data from 163 dyads. Results: Seventy-three infants developed atopy. Forty-one were diagnosed with AD (25%), 33 developed food allergy (20%), and 10 had wheezing (6%). Eleven developed >1 condition (7%). Infants who did not develop atopy consumed higher concentrations of miR-375–3p (d = 0.18, P = 0.022, adj P = 0.044) and miR-148b-3p (d = 0.23, P = 0.007, adj P = 0.028). The consumption of miR-375–3p (X² = 5.7, P = 0.017, OR: 0.92, 95% CI: 0.86, 0.99) was associated with reduced atopy risk. Concentrations of miR-375–3p increased throughout lactation (r = 0.46, F = 132.3, P = 8.4 × 10⁻³⁴) and were inversely associated with maternal body mass (r = –0.11, t = –2.1, P = 0.032). Conclusions: This study provides evidence that infant consumption of miR-375–3p may reduce atopy risk.