Author ORCID Identifier

https://orcid.org/0000-0001-9000-829X

Date of Award

12-11-2023

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience Institute

First Advisor

Anne Z. Murphy

Second Advisor

Laura Carruth

Third Advisor

Benoit Chassaing

Fourth Advisor

Nancy Forger

Abstract

Since 2000, the rate of opioid use and abuse by women of reproductive age has increased exponentially, resulting in a five-fold increase in the number of infants exposed to opioids in utero. Perinatal opioid exposure is associated with an increased risk of hospitalization and infection, suggesting that chronic exposure to opioids across gestation negatively impacts immune function. Opioid-induced immunocompromise may be due to a direct inhibitory action on immune cells, or indirectly via multiple central nervous system pathways. Opioids also negatively influence the gut microbiota, which serves as an essential immune stimulator. Remarkably few studies have examined the impact of perinatal opioid exposure (POE) on immune system development and function, or gut microbiota composition, and none have utilized a clinically relevant model that recapitulates opioid use disorder in women of reproductive age. Our studies directly address this gap and investigate the influence of in utero opioid exposure on basal immune function and response to an immune stimulator in adult male and female rats. The impact on the gut microbiota was examined as well. Here, we report that the febrile and neuroinflammatory response to an immune stimulator, lipopolysaccharide, is potentiated by perinatal opioid exposure, likely via suppressed baseline immune response, including a reduction in antibody production. We also report that perinatal morphine alters gut microbiota composition and significantly decreases microbial maturity. These changes in gut microbiota composition likely contributed to the observed deficits in immune system function. Together, this suggests that in utero opioid exposure influences gut microbiota composition and suppresses immune system development, increasing susceptibility to infection. Further investigation into the mechanisms whereby opioid exposure compromises immune system development is critical for the identification of potential interventions.

DOI

https://doi.org/10.57709/36202485

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