Impact of breast milk miR-155 on the health of preterm neonates

Abstract

Background. Breast milk (BM) is an important source of microRNAs (miRs). MicroRNAs are highly resistant to gastrointestinal enzymes and are well absorbed in the intestine. MiR-155 is one of the most expressed miR of BM. Currently, the effect of miR-155 of BM on the health of preterm neonates has not been almost studied. The objective was to determine the effect of miR-155 of BM on the health of preterm neonates. Materials and methods. We examined 74 newborns, who were treated in neonatal departments. We determined the level of miR-155 in the BM of 44 mothers of exclusively breastfed children. In parallel, we evaluated gene expression of the transcription factor FOXP3 in buccal smears of all neonates. Three comparison groups were selected: group 1 consisted of 32 newborns of up to 37 weeks of gestation; group 2 — of 30 preterm newborns on artificial feeding; control group — of 12 full-term breastfed newborns. Results. The gestational age median in group 1 was 33 (31; 34) weeks; in group 2 — 32.5 (32; 35) weeks; it was higher in the control group (p < 0.001) — 40 (39; 41) weeks. Neonatal encephalopathy as the main diagnosis occurred more often among full-term newborns (p < 0.001). Children of groups 1 and 2 did not differ significantly in the frequency of respiratory distress syndrome and the duration of the necessary respiratory support (p > 0.05). In group 2 compared to group 1, manifestations of necrotizing enterocolitis were detected significantly more often (p < 0.05): 30.0 ± 8.4 % vs 9.4 ± 5.2 %. The results of evaluating the miR-155 expression level in the BM of mothers of group 1 children prove that the corresponding indicator in the control group was exceeded by an average of 6.2 (4.1; 9.2) times (p < 0.001). Analysis of FOXP3 levels in buccal smears showed that all preterm newborns had significantly lower FOXP3 levels than that of full-term neonates (< 0.001). However, the expression of this factor was the lowest in group 2 (< 0.001): 0.08 (0.04; 0.16) c.u. in group 2 vs 0.21 (0.14; 0.38) c.u. in group 1. We found a direct moderate correlation between the expression levels of miR-155 of the BM and the FOXP3 in the mucosal cells of breastfed preterm neonates: r = 0.442 (p = 0.014). A significant decrease was noted in the expression of FOXP3 in children with necrotizing enterocolitis (0.11 (0.04; 0.25) c.u.) compared to newborns without such pathology (0.22 (0.09; 0.91) c.u.) (p < 0.05). Conclusions. The results of the study confirm a lower number of necrotizing enterocolitis cases among preterm breastfed babies. BM of mothers, whose children were born prematurely, has a higher level of miR-155 expression, which promotes FOXP3 expression of mucous membranes. Thus, it is likely that miR-155 of BM stimulates maturation and maintains the level of T-reg cells of the mucous membranes that prevents the development of necrotizing enterocolitis in premature infants.