Opioid Receptors Play Unexpected Role in Gut Development

Image of a network of colorful neurons in the brain.
STUDY: Research reveals surprising role of opioid receptors in gut nerve development, challenging past understanding and offering promise for new digestive disease treatments.

The enteric nervous system (ENS), sometimes known as the “brain in the gut,” is developing, and researchers have found a novel function for opioid receptors in this process. This discovery casts doubt on the accepted knowledge of opioid receptors and emphasizes their importance beyond the treatment of pain and addiction.

Opioid receptors are essential for the development of gut neurons, according to a study that employed zebrafish embryos. This finding may affect congenital digestive disease treatments.

Important Details:

The enteric nervous system’s development depends on opioid receptors.

The migration and maturation of gastrointestinal neurons are impacted by the disruption of these receptors.

New treatments for congenital digestive diseases could result from these findings.

Rice University is the source.

A previously unidentified role for opioid receptors in the development of the enteric nervous system (ENS), sometimes termed as the “brain in the gut,” has been discovered by Rice University researchers.

This finding casts doubt on the conventional knowledge of opioid receptors and highlights their importance beyond addiction and pain relief.

Under the direction of Rosa Uribe, an assistant professor of biosciences at Rice University and a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar, the research team used zebrafish embryos, which have many genetic similarities to humans, to conduct a series of experiments that helped identify the genes essential for ENS development.

An essential part of controlling digestive processes is the ENS, a network of neurons in the gastrointestinal tract.

The team’s findings were released on May 29 in the journal PLOS ONE.

“We found that the opioid signaling pathway is necessary for the gut’s developing nervous system, an area of the body that has received little research attention,” Uribe stated.

To see how these genetic changes affected the development of gut nerves, the researchers used gene-editing methods to remove, or knock out, a single gene from a population of zebrafish embryos. This procedure uncovered new genes linked to the development of ENS, including those encoding opioid receptors.

In contrast to what was previously believed, the researchers discovered that opioid receptors play a crucial role in the development of gut nerves as well as pain perception and addiction.

According to Uribe, “the migration and maturation of enteric neurons along the gut were disrupted when these receptors were deactivated.” The significance of opioid signaling pathways in the formation of the ENS is demonstrated by that disruption.

The research team’s discoveries provide fresh perspectives on gut health and illness. The fact that many newborns born without gut nerves have trouble passing feces emphasizes how this research may affect pediatric medicine. Novel therapies for congenital digestive diseases may be made possible by a better understanding of the role that opioids play in gut development.

“Our research unveils a new aspect of opioid receptor function and highlights their unexpected role in gut development,” Uribe said. “This could have profound implications for understanding digestive disorders and potentially lead to new therapeutic approaches.”

In addition, the study found additional genes that may have an impact on gastrointestinal health, namely VGF. Lead researcher and postdoctoral scholar Rodrigo Moreno Campos stated that additional research in this field may provide further understanding of the intricate interactions among genes, the brain system, and digestive function.

“Our finding is incredible and opens up a whole new avenue of enteric neurodevelopmental biology research in the field,” Moreno Campos said. “The implications for congenital, neurological, and metabolic disease are great.”

As a CPRIT Scholar, Uribe enrolled at Rice in 2017. She graduated from San Francisco State University with a bachelor’s degree in cell and molecular biology in 2006 and the University of Texas at Austin with a doctorate in molecular cell and developmental biology in 2012. She received an NSF CAREER Award in 2020.

For more information: A targeted CRISPR-Cas9 mediated F0 screen identifies genes involved in the establishment of the enteric nervous system, PLOS ONE, https://doi.org/10.1371/journal.pone.0303914 

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