Dysregulation of miR-146a in human milk of mothers having children with autism.

Abstract

Autism spectrum disorder (ASD) is a set of neurobehavioral manifestations that impose poor social interaction and stereotyped repetitive patterns. Several mircoRNA (miRNA) dysregulations underpin ASD pathophysiology via impairing the neurogenic niches. For instance, miR-146a and miR-106 differential expressions are linked to deregulation of ASD-related genes and the severity of clinical symptoms, respectively. Breastfeeding provides newborns with many bioactive compounds that support their neurodevelopment including miRNA. Our pilot study evaluated the expression pattern of miR-106a and miR-146a in human milk (HM) of nursing mothers (n = 36) having autistic children compared to age-matched counterparts (n = 36) with neurotypical children as controls. Under sterile conditions, breast milk samples were collected using manual sucking pumps and centrifuged to separate the fat layer. Total RNA was extracted from the lipid fraction, and the expression profiles of both miR-106a and miR-146a were evaluated using quantitative real-time polymerase chain reaction. Among the test group, we reported some factors that were previously linked to HM miRNA perturbations: gestational diabetes, hypertension, and cesarean delivery. HM miR-106a showed comparable expression levels in both mother groups (p = 0.8681), whereas HM miR-146a was significantly downregulated in mothers with autistic children compared to controls (p = 0.0399). Alternatively, HM miR-106 levels were positively associated with two ASD clinical parameters: Childhood Autism Rating Scale (CARS) and communication and language domain of Autism Diagnostic Interview-Revised (ADI-R) (r = 0.6452, p = 0.0003 and r = 0.3958, p = 0.0410, respectively). The receiver operating characteristic (ROC) curves of both maternal HM miR-106a and miR-146a showed poor fitness as predictive biomarkers for ASD. Our findings suggest that the miR-146a differential expression in ASD children may originate at infancy during the lactation period. Thus, maternal pre- and postnatal health care is critical to maintain optimal miRNome in breast milk.