Poster #16 - Gut Microbiota in Infants Exposed to Opioids In Utero

• In Event: Poster Session 14

Abstract

Introduction

Approximately 6% of people use opioids during pregnancy and opioid-related diagnoses such as neonatal opioid withdrawal syndrome have increased 131% (CDC, 2020; 2021). Prenatal opioid exposure has been associated with changes in brain development and risk for later neurobehavioral disorders (8, 9). One potential mechanism to explain the potential relationship between prenatal opioid exposure and infant outcomes is the gut microbiome-gut-brain axis. The development of balanced gut microbiota during infancy lays the groundwork for overall health in infancy and adulthood (Turroni et al. 2022). Animal models indicate that prenatal exposure to opioids may induce an imbalance in gut microbiota (Abu et al., 2021; Grecco et al., 2021). In addition to basic gut microbiota changes, Lyu and colleagues (2022) found these bacterial changes were associated with neurobehavioral alternations in the rodents. It remains unknown whether a similar pattern is present in human infants. This study compared gut microbiota between human newborns with prenatal opioid exposure and human newborns without prenatal opioid exposure. Moreover, correlational analyses examined whether bacterial alterations were associated with infant neurobehavior assessed shortly after birth.


Methods

Stool samples from eleven infants with prenatal opioid exposure and five infants without prenatal opioid exposure were collected and stored at -80 degrees Celsius. This sample of infants represents a subset of infants from within a larger study.

Microbiota composition analysis included using QIIME2 to process 16s RNA data, analyze quantitative, and phylogenetic qualitative measures of alpha and beta diversity and to perform a permutational multivariate analysis of variance analysis of microbiomes (PERMANOVA) for identification of differential abundances. Data analysis was generated using SAS software.

The NICU Network Neonatal Scale (NNNS; Tronick & Lester, 1996) was performed on all infants as part of their participation in the larger study.


Results

General microbiome features. Based on the operational taxonomic unit (OUT) bar plot, differences were observed in Beta-diversity based on opioid exposure (Figure 1). PCoA plots showed greater segregation between opioid exposed and non-opioid exposed infants with PERMANOVA p-value of .023 (Figure 2).

Correlational Analyses. Using variation across the top component from the Beta-diversity estimation (Bray-Curtis) and infants’ NNNS subscale scores, several associations were significant. Higher beta-diversity was related to lower attention [r(15) = -.71, p = .003] and self-regulation [r(15) = -.64, p = .01], and higher handling [r(15) = .69, p = .005] and excitability [r(15) = .77, p < .001].


Conclusions

Findings demonstrate general gut microbiota differences across infants exposed to opioid during pregnancy and infants not exposed to opioids during pregnancy. The relative abundance of specific species of bacteria differs across groups. The relations between beta-diversity estimation and infants’ attention, self-regulation, handling, and excitability scores from the NNNS may indicate an important role for gut microbiota in understanding and addressing infant neurobehavior. The identification of specific species of bacteria that are present in infants with prenatal opioid exposure can guide treatment protocols to address the imbalance of gut microbiota and potentially reduce withdrawal symptoms and improve infant outcomes.

Authors

• Alyson Chroust, East Tennessee State University
  Presenting Author

• Kara Boynewicz

• Kristy Thomas

• Amy Wahlquist

• William A. Clark