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

Abstract

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 four microRNAs (miR-146b-5p, miR-148b-3p, miR-21–5p, and miR-375–3p) in human milk would be associated with reduced atopy risk. Design The Breast Milk IMPACT Study involved a cohort of mother-infant dyads who planned to breastfeed beyond four months. Infant consumption of the four human milk microRNAs in the first six months was calculated as the product of milk microRNA concentration and the number of human milk feeds, across three lactation stages: early milk (0–4 weeks), transitional milk (4–16 weeks), and mature milk (16–24 weeks). The primary outcome was infant atopy in the first year, defined as atopic dermatitis, food allergies, or wheezing. The final analysis included 432 human milk samples and 7,824 weeks of longitudinal health data from 163 dyads. Results Seventy-three infants developed atopy. Forty-one were diagnosed with atopic dermatitis (25%), 33 developed food allergy (20%), and 10 had wheezing (6%). Eleven developed > 1 condition (7%). Infants who did not develop atopy consumed higher levels 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). 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. Levels 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.

Multi-Omic Factors Associated with Frequency of Upper Respiratory Infections in Developing Infants

“…Intriguingly, miR-22-5p levels appear to potentiate the protective effect of sustained breastfeeding. This is consistent with prior studies suggesting that maternal-infant transfer of miRNAs in breastmilk may impact immune development [ 39 ]. It also supports prior studies implicating miR-22 expression in upper respiratory infections, pneumonia, and asthma [ 40 , 41 ].…”

“…This study involved a subset of infants from a prospective longitudinal cohort of 221 mother-infant dyads [ 39 ]. Eligibility criteria were term delivery (37–42 weeks gestation) and plan to breastfeed ≥ four months.…”

Breast milk microRNAs: Potential players in oral tolerance development

“…Similarly, Hicks et al. ( 16 ) recently showed that breast milk miR-375 seem to decrease the risk of atopy in breastfed infants; a miRNA that did not make it on to our top 10 list. Nevertheless, while acknowledging this as a potential shortcoming, we believe that adhering to a systematic approach in selecting which miRNAs to focus on adds rigor to this review.…”

“…Although the biological relevance remains to be clarified, this conservation of sequence suggest that miRNAs serve fundamental functions. Like other breast milk components, the miRNA profile seems to vary over time, displaying daily as well as more long-term fluctuations ( 14 , 16 , 17 ), although empirical data is still scarce. An astonishing >1,900 different types of miRNAs have been detected in human breast milk, with potential biological implications on cell communication, fatty acid biosynthesis, regulation of actin skeleton and a vast number of immunological pathways ( 12 ).…”

The Association between Infant Colic and the Multi-Omic Composition of Human Milk

“…This study involved a secondary analysis of data collected as part of the Breast Milk IMPACT (Influence of the Micro-transcriptome Profile on Atopy in Children over Time) Study [ 28 ]. The Breast Milk IMPACT study involved a convenience sample of 221 breastfeeding infants enrolled within 7 days of delivery and followed until 12 months of age.…”