Brief Hydromorphone Exposure During Pregnancy Sufficient to Induce Maternal and Neonatal Microbial Dysbiosis

Prenatal opioid exposure is associated with significantly adverse medical, developmental, and behavioral outcomes in offspring, though the underlying mechanisms driving these impairments are still unclear. Accumulating evidence implicates gut microbial dysbiosis as a potential modulator of these adverse effects. However, how opioid exposure during pregnancy alters the maternal and neonatal microbiome remain to be elucidated. Here, we utilize a murine model of brief hydromorphone exposure during pregnancy (gestation day 11-13; i.p.; 10 mg/kg) to examine its impact on the maternal and neonatal microbiome. Fecal samples were collected at various timepoints in dams (4 days post hydromorphone exposure, birth, and weaning) and offspring (2, 3, and 5 weeks) to interrogate longitudinal changes in the microbiome. Stomach contents at 2 weeks were also collected as a surrogate for breastmilk and microbial analysis was performed using 16S rRNA sequencing. Alongside alterations in the maternal gut microbial composition, offspring gut microbiota exhibited distinct communities at 2 and 3 weeks. Furthermore, functional profiling of microbial communities revealed significant differences in microbial community-level phenotypes gram-negative, gram-positive, and potentially pathogenic in maternal and/or neonatal hydromorphone exposed groups compared with controls. We also observed differences in stomach microbiota in opioid-exposed vs non-exposed offspring, which suggests breast milk may also play a role in shaping the development of the neonatal gut microbiota. Together, we provide evidence of maternal and neonatal microbial dysbiosis provoked even with brief hydromorphone exposure during pregnancy.