Anti-inflammatory effect of breast milk miR-148a on the state of mucous membranes in premature newborns

Background. Breast milk (BM) is an optimal nutritional product for newborns and a source of exogenous microRNAs (miR). MiR-148a is one of the most highly expressed miR of BM. Currently, there is a lack of data on the miR-148a effect on the development of necrotizing enterocolitis (NEC) in premature newborns. The purpose of the study was to determine the influence of miR-148a of the mother’s BM on the risk of NEC development in preterm newborns. Materials and methods. We examined 74 newborns, who were treated in neonatal departments. We determined the level of miR-148a in the BM of 44 mothers of exclusively breastfed children. In parallel, we evaluated gene expression of the transcription factor T-bet in scrapings of the buccal mucosa of all the newborns. Three groups for comparison were selected: group 1 consisted of 32 newborns up to 37 weeks of gestation on breastfeeding (BF); group 2 — of 30 preterm newborns on artificial feeding; the control group — 12 full-term newborns on BF. Results. The gestational age median of group 1 children was 33 (31; 34) weeks; group 2 — 32.5 (32; 35) weeks; and it was comparatively 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 cases of respiratory distress syndrome and neonatal encephalopathy (p > 0.05). In group 2 compared to the first one, manifestations of NEC occurred significantly more often (p < 0.05): 9/30.0 ± 8.4 % vs 3/9.4 ± 5.2 %. We determined that the level of ­miR-148a expression in the BM of the mothers of premature children on BF was significantly lower (p < 0.001) than in the group of full-term children: 0.089 (0.048; 0.142) c.u. vs 1.0 (1.0; 1.0) c.u. Furthermore, the level of the transcription factor T-bet expression in the cells of the buccal mucosa scrapings was higher in premature children with clinical NEC (p = 0.022): 2.36 (1.94; 3.17) c.u. vs 1.49 (1.0; 3.27) c.u. in children without signs of NEC. We proved the presence of direct positive correlation between the T-bet level and NEC manifestations (r = 0.271; p = 0.021) and determined the inverse correlation between the level of miR-148a expression in the mother’s BM and the level of T-bet expression (r = –0.371; p = 0.043). Conclusions. The miR-148a expression level is relatively lower in the BM of the mothers whose children were born prematurely and have problems with adaptation than in the mothers who gave birth at term. However, in case of NEC development, there is an increase of miR-148a level in the mother’s BM, which contributes to a decrease in the T-bet expression in the mucous membranes of the child and has a protective impact on intestinal walls.