Exposure to opioids before birth may lead to neurological and behavioral changes later in life

Summary: Opiates affect the gut microbiome of developing fetuses, altering metabolic pathways and increasing the risk of neurological and behavioral differences later in life.

source: University of Missouri Columbia

While exposure to opioids before birth has been linked to adverse health outcomes, a new study at the University of Missouri finds that exposure to opioids before birth can lead to long-term neurological or behavioral effects later in a baby’s life.

The key is the effect of opioids on the growth of the fetus’s gut microbiome – the collection of bacteria and other microorganisms that live naturally within the guts of all humans and animals and can serve as a measure of overall health and wellness.

Cheryl Rosenfeld, a professor at MU College of Veterinary Medicine, teamed up with Trupti Joshi, assistant professor at MU College of Medicine, to compare the gut microbiome of adult mice that were exposed during pregnancy to oxycodone, a commonly used opioid that treats uterine pain, with the gut microbiome of mice that had not. You are exposed to any opioids.

“Opioids are increasingly being prescribed to pregnant women to treat pain, but when they are taken, we learn that it is not only the mother who is exposed, but also the fetus at a time when its organs are still developing,” Rosenfeld said. .

“These findings highlight the potential long-term health effects of offspring, not only at birth, but also in adulthood.”

After collecting fecal material from the two groups of mice at 120 days of age, the researchers identified significant changes and disruptions in the normal balance of bacteria in the intestines of mice exposed to oxycodone in the womb. These changes have been associated with changes in metabolic pathways, affecting metabolism and possibly long-term neurological and behavioral health.

Rosenfeld added that the gut microbiome of humans is very similar to the gut microbiome of mice, making the animal a useful biomedical model for translational and precision medicine research.

“While this research could lead to human studies in the future, these could take 20 to 30 years due to the longer lifespan of humans compared to mice,” Rosenfeld said.

“The opioid epidemic, one of the largest public health crises facing the United States, is causing real harm right now, so our goal is to raise immediate awareness and hopefully protect the health and well-being of women who are currently pregnant or seeking to become pregnant and their offspring from potential and long-term negative effects. for opiates.

The research is personal to Rosenfeld, who was her niece in the womb when her sister-in-law was given Quaaludes to relieve anxiety. While her niece was born healthy and seemed fine early in childhood, she later developed respiratory problems, neurological problems and behavioral abnormalities in her teen years, and now lives in a nursing home in her 30s.

“For these children who were exposed to opioids in the womb, there is now also an increased risk for them to become addicted to opioids themselves, so I am concerned about them as they progress into adulthood,” Rosenfeld said.

This shows a pregnant woman
The study links changes in gut bacteria to prenatal exposure to oxycodone, an opiate commonly abused during pregnancy.

“We hope by identifying these associations as soon as possible, potential interventions can be developed and alternative treatment options to be discussed for managing pain in pregnant women.”

Joshi, a bioinformatics scientist in the Department of Health Management and Informatics at MU School of Medicine, was a clinical physician who occasionally helped with pregnancies in India before coming to the United States to study bioinformatics.

“Genomic sequencing technology, bioinformatics tools, and computational techniques can be applied together to help us as researchers begin to find links between physiology and our health in general,” Joshi said.

We are beginning to learn how changes in the gut microbiome can affect one’s mood and mental health later in adulthood. This research helps us begin to better understand the gut-brain axis, as there is a lot of communication between the brain, the central nervous system, the endocrine system, the immune system, and the gut microbiome. “

“Long-term effects of developmental exposure to oxycodone on the gut microbiota and the relationship to adult behavior and metabolism” was recently published in American Society for Microbiology.

Financing: Funding was provided by the National Institute of Environmental Health Sciences. Study co-authors include Zane Liu, Robert Schmidt, Rachel Martin, Madison Green, Jessica Kinkade, Judy Mau and Nathan Bivens.

About this pregnancy and research news about opioids

author: Brian Consiglio
source: University of Missouri Columbia
Contact: Brian Consiglio – University of Missouri Columbia
picture: The image is in the public domain

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original search: open access.
Long-term effects of developmental exposure to oxycodone on the gut microbiota and the relationship to adult behavior and metabolismBy Sheryl Rosenfeld et al. mSystems


Long-term effects of developmental exposure to oxycodone on the gut microbiota and the relationship to adult behavior and metabolism

Opioid medications are commonly prescribed as a sedative for pregnant women. Direct exposure to such drugs may slow bowel movement, alter intestinal permeability, and affect the gut microbiome. While such drugs affect the gut microbiome of infants, no study to date has determined whether developmental exposure to such drugs leads to long-term effects on the gut microbiome and thus on host responses.

We hypothesized that developmental exposure to oxycodone (OXY) leads to lasting effects on the gut microbiota and that these changes are associated with neurobehavioral and metabolic changes in adults.

Female rats were treated daily with 5 mg oxy/kg or saline (control group [CTL]) for two weeks before reproduction and then throughout pregnancy.

Male and female pups were weaned, tested with a combination of behavioral and metabolic tests, and fecal polyps were collected at adulthood (120 days of age). In females, relative abundance Potricemonas spp, bacteria, anaerobic spp. , TM7, Enterococci spp. and Clostridia were larger in OXY versus CTL individuals.

In males, the relative abundance of Coriobacteriaceae, roseola Prosecution. , Sutrila spp. and Clostridia in oxidative stress-prone individuals. Bacterial changes were also associated with predictive changes in the metabolite pathway that also differed according to sex. In males and females, infected gut microbiota is associated with metabolic changes but not behavioral changes.

The results suggest that evolutionary exposure to oxygen leads to lasting effects on the adult gut microbiota that may influence host metabolism, possibly through specific bacterial metabolites or other bacteria-derived products.

More work is needed to describe how evolutionary exposure to OXY affects host responses through the gut microbiome.