title: Human Breast Milk miRNA, Maternal Probiotic Supplementation and Atopic Dermatitis in Offspring.
abstract: BACKGROUND
  Perinatal probiotic ingestion has been shown to prevent atopic dermatitis (AD) in infancy in a number of randomised trials. The Probiotics in the Prevention of Allergy among Children in Trondheim (ProPACT) trial involved a probiotic supplementation regime given solely to mothers in the perinatal period and demonstrated a ~40% relative risk reduction in the cumulative incidence of AD at 2 years of age. However, the mechanisms behind this effect are incompletely understood. Micro-RNAs (miRNA) are abundant in mammalian milk and may influence the developing gastrointestinal and immune systems of newborn infants. The objectives of this study were to describe the miRNA profile of human breast milk, and to investigate breast milk miRNAs as possible mediators of the observed preventative effect of probiotics.
  
  
  METHODS
  Small RNA sequencing was conducted on samples collected 3 months postpartum from 54 women participating in the ProPACT trial. Differential expression of miRNA was assessed for the probiotic vs placebo and AD vs non-AD groups. The results were further analysed using functional prediction techniques.
  
  
  RESULTS
  Human breast milk samples contain a relatively stable core group of highly expressed miRNAs, including miR-148a-3p, miR-22-3p, miR-30d-5p, let-7b-5p and miR-200a-3p. Functional analysis of these miRNAs revealed enrichment in a broad range of biological processes and molecular functions. Although several miRNAs were found to be differentially expressed on comparison of the probiotic vs placebo and AD vs non-AD groups, none had an acceptable false discovery rate and their biological significance in the development of AD is not immediately apparent from their predicted functional consequences.
  
  
  CONCLUSIONS
  Whilst breast milk miRNAs have the potential to be active in a diverse range of tissues and biological process, individual miRNAs in breast milk 3 months postpartum are unlikely to play a major role in the prevention of atopic dermatitis in infancy by probiotics ingestion in the perinatal period.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00159523.
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Melanie Rae
authors.initials: MR
authors.lastname: Simpson
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Gaute
authors.initials: G
authors.lastname: Brede
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Jostein
authors.initials: J
authors.lastname: Johansen
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Roar
authors.initials: R
authors.lastname: Johnsen
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Ola
authors.initials: O
authors.lastname: Storrø
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Computer and Information Science, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Sætrom
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Øien
mesh_terms: D000328:Adult; D003876:Dermatitis, Atopic / Q000517:prevention & control*; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000378:metabolism*; D008895:Milk, Human / Q000378:metabolism*; D018743:Perinatal Care; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D019936:Probiotics / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*
chemical_list: D035683:MicroRNAs