Maternal psychological distress, breast milk extracellular vesicles, and infant immunity: A translational study

Distress during early postnatal life has a potential impact on maternal mental health and related biological systems. However, the potential biological roles of these systems' modifications remain largely unknown. Bronchiolitis represents a life-threatening condition for infants and a possible stressful event for mothers with an impact on maternal breast milk composition and potentially on infants'health. In this framework purposes of the present study were: a) to evaluate the impact of infants' severe bronchiolitis on maternal mental health; b) to examine the correlation between maternal mental health status and extracellular vesicles (EVs) in breast milk; c) to explore the impact of breast milk EVs modification on the infant's innate immunity. We hypothesize that severe infant illness acts as a maternal stressor, which in turn remodels the composition of breast-milk EVs, thereby modulating immune response in the infant affected by bronchiolitis. A prospective, observational study with a case-control design and a longitudinal observation component was conducted. The case group included dyads of mothers and infants, with the infants admitted to the pediatric emergency department for severe bronchiolitis, while the control group consisted of healthy mother-infant dyads. The two groups were evaluated at baseline (admission for bronchiolitis for cases) and after one month. In both the appointments clinical data including mental health status by validated scales and a breast milk sample were collected. Biological analyses included extracellular vesicles (EVs) isolation and characterization, and the use of zebrafish to study the EVs-mediated modulation of innate immunity. Baseline mental health assessment revealed markedly higher scores in the case group for depressive symptoms (p < 0.01) and state anxiety (p < 0.01). These symptoms ameliorated over time in the case group. At baseline, cases showed higher concentrations of CD177⁺ EVs compared to controls (p = 0.02). Among T cell-derived EVs, CD4⁺ vesicles were significantly more abundant in cases than controls at follow-up (p = 0.04). At baseline maternal functioning was inversely associated with several EV subtypes. Finally, the treatment of zebrafish embryos with baseline EVs of cases with low level of anxiety resulted in a significant increase in neutrophil recruitment. This study suggests the existence of a complex interplay between stressful events, maternal mental health and innate immune modulation of infants with an acute infectious disease. New studies are needed to confirm the results of the present research.