Experiences of stress early in life may disrupt the gut-brain connection and increase the risk of digestive disorders years later.
A new study published in Gastroenterology suggests that stress during early development could increase the risk of digestive problems later in life. The researchers found that these long-term effects are tied to changes in both the gut and the sympathetic nervous system.
“Our research shows that these stressors can have a real impact on a child’s development and may influence gut issues long-term. Understanding the mechanisms involved can help us to create more targeted treatments,” said study author Kara Margolis, director of the NYU Pain Research Center and professor of molecular pathobiology at NYU College of Dentistry and pediatrics and cell biology at NYU Grossman School of Medicine.
Early Stress, Brain Development, and Mental Health
Experiences such as emotional neglect and other early hardships can strongly influence a child’s development. Research indicates that stress before and after birth can affect how the brain develops and increase the chances of conditions like anxiety and depression later in life.
To explore how this stress might also affect digestion, scientists at NYU College of Dentistry’s Pain Research Center focused on the connection between the brain and the gut. This communication system is essential for normal digestion. When it is disrupted, it can lead to problems such as irritable bowel syndrome, abdominal pain, and motility issues (e.g., constipation or diarrhea).
“When the brain is impacted, the gut is likely also impacted—the two systems communicate 24 hours a day, seven days a week,” said Margolis. “There’s some data showing that early life stress may be linked to gut disorders, but we wanted to take an in-depth look at the mechanisms and how these gut-brain pathways work.”
Mouse Study Reveals Long-Term Effects of Early Stress
The researchers examined early life stress using three approaches, including animal models and two large studies involving children.
In the mouse experiments, newborn mice were separated from their mothers for several hours each day to simulate early stress. When studied months later (at the equivalent of young adulthood), these mice showed more anxiety-like behavior, increased gut pain, and abnormal gut movement. The type of motility problem varied by sex, with female mice more likely to develop diarrhea and males more likely to experience constipation.
Further testing showed that different biological systems may be responsible for different symptoms. Disrupting sympathetic nerve signals improved motility but did not reduce pain. In contrast, sex hormones influenced pain but not motility. Pathways involving serotonin appeared to affect both pain and gut movement.
“This suggests that there’s no one-size-fits-all approach to treating disorders of gut-brain interaction, and that when patients experience different symptoms, we may have to target different pathways,” said Margolis.
Human Studies Link Early Stress to Digestive Disorders
The patterns seen in animal studies were also reflected in two large human datasets. One analysis followed more than 40,000 children in Denmark from birth to age 15. About half of these children were born to mothers who experienced untreated depression during or after pregnancy.
Children whose mothers had untreated depression were more likely to develop digestive conditions such as nausea and vomiting, functional constipation, colic, and irritable bowel syndrome. These findings build on earlier research led by Margolis showing that children of mothers who took antidepressants during pregnancy had a higher likelihood of being diagnosed with functional constipation.
“Digestive outcomes for children seem to be even more profound when a mother’s depression is left untreated, suggesting that mothers experiencing depression should be treated during pregnancy. This may include nonmedical measures like therapy, but some pregnant women may also require medications to treat their depression,” said Margolis. “This finding also reinforces our commitment to developing antidepressants that do not reach the placenta—a focus of many of our studies right now.”
A second study used data from nearly 12,000 children in the US who were part of the NIH-funded Adolescent Brain Cognitive Development (ABCD) study. Researchers examined adverse childhood experiences, including abuse, neglect, and parental mental health issues, and compared them with digestive symptoms at ages nine and 10. They found that gastrointestinal problems increased with any form of early life stress.
Gut-Brain Connection and Future Treatments
Unlike the mouse experiments, the human studies did not show differences between males and females in digestive outcomes. This suggests that early stress may affect gut and brain health similarly across sexes during key developmental stages.
Overall, the findings indicate that early life stress can influence how the brain and gut communicate, contributing to long-term digestive issues such as pain and abnormal motility. By identifying that different biological pathways control different symptoms, the research opens the door to more precise treatments for disorders of gut-brain interaction.
“When patients come in with gut problems, we shouldn’t just be asking them if they are stressed right now; what happened in your childhood is also a really important question and something we need to consider,” said Margolis. “This developmental history could ultimately inform how we understand how some disorders of gut-brain interaction develop and treat them based on specific mechanisms.”
Reference: “Enteric and Sympathetic Nervous System Pathways Mediate Early Life Stress Effects on Gut Motility and Pain: Mechanistic Findings With Human Correlation” by Sarah A. Najjar, Helene Kildegaard, Ardesheer Talati, Priscila Dib Goncalves, Andrew Del Colle, Zixing Huang, Yan Tong, Daniel Juarez, Rahi Shah, Erfaneh Barati, Taeseon Woo, Melissa Medina, Narek Israelyan, Marguerite Bernard, Ruxandra Tonea, Michelle Ovchinsky, Noa Pesner, Roey Ringel, Luisa Valdetaro, Mette Bliddal and Kara G. Margolis, 16 March 2026, Gastroenterology.
DOI: 10.1053/j.gastro.2026.02.030
Additional study authors include Sarah Najjar (first author), Zixing Huang, Yan Tong, Daniel Juarez, Rahi Shah, Erfaneh Barati, Taeseon Woo, Melissa Medina, Michelle Ovchinsky, Noa Pesner, Luisa Valdetaro, and Lin Hung (co-senior author) of NYU Dentistry; Ardesheer Talati, Priscila Dib Goncalves, Andrew Del Colle, Narek Israelyan, Marguerite Bernard, Ruxandra Tonea, Roey Ringel, and Michael Gershon of Columbia University; and Helene Kildegaard, Mette Bliddal, and Martin Thomsen Ernst of the University of Southern Denmark.
The research was supported by the National Institutes of Health (R01 DK130517, R01MH119510, K01DA057389, F32DK132810, K01DK144656, R01DK130518, R01DK126644) and Department of Defense (W911NF-21-S-0008, PR160365), as well as the NARSAD/Brain Behavior Research Foundation; Alpha Omega Alpha; North American Society for Pediatric Gastroenterology, Hepatology and Nutrition; and the American Gastroenterological Association Research Foundation (AGA2024–51–02).
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