Neonatal Morphine Results in Long-Lasting Alterations to the Gut Microbiome in Adolescence and Adulthood in a Murine Model

Abstract

Despite the many advancements in the field of pain management, the use of intravenous opioids, such as morphine, in neonates is still a challenge for clinicians and researchers, as the available evidence concerning the long-term consequences of such an early exposure is limited. In particular, little is known concerning the long-term consequences of neonatal morphine exposure on the gut microbiome, which has been identified as a key modulator of health and diseases. Consequently, the purpose of this study was to investigate those long-term consequences of neonatal morphine on the gut microbiome. Newborn mice were exposed to either morphine (5 mg/kg/day) or saline for a duration of 7 ± 2 days. Fecal samples were collected during adolescence and adulthood to longitudinally assess the gut microbiome. DNA extracted from the stool samples were sent out for 16s rRNA sequencing. During adolescence, neonatal morphine resulted in a significant increase of α-diversity and an overall decrease in the abundance of several commensal genera. During adulthood, β-diversity revealed a significantly different microbial composition of the neonatally morphine-exposed mice than that of the controls. The results demonstrate that morphine exposure during this critical developmental period resulted in long-lasting changes, particularly a reduction in several commensal bacteria. Thus, an adjunct therapeutic intervention with probiotics could potentially be used along with opioids to manage pain while attenuating the long-term co-morbidities of neonatal morphine later in life.