Scientists Link Childhood Stress to Lifelong Digestive Problems

A new study published in the journal Gastroenterology suggests that stress in early childhood may increase the risk of digestive problems later in life. The researchers found that these effects are linked to changes in both the gut and the sympathetic nervous system.

How Early Stress Shapes Brain and Gut Development

“Our research shows that these stress factors have a real impact on a child’s development and can influence gut problems in the long term. Understanding the mechanisms involved can help us develop more targeted treatments,” explained study author Kara Margolis, director of the NYU Pain Research Center and professor of molecular pathobiology at NYU College of Dentistry, as well as of pediatrics and cell biology at NYU Grossman School of Medicine. Experiences such as emotional neglect and other forms of adversity can significantly impact a child’s development. Studies suggest that stress during pregnancy and early childhood can impair brain development and increase the risk of mental health conditions such as anxiety and depression.

To better understand this connection, researchers at the Pain Research Center at NYU College of Dentistry investigated how early-life stress affects communication between the brain and the gut. This connection plays a key role in digestion, and disruptions can lead to conditions such as irritable bowel syndrome, abdominal pain, and motility issues (e.g., constipation or diarrhea). “If the brain is affected, the gut is likely affected too—the two systems communicate 24 hours a day, seven days a week,” said Margolis. “There is some data suggesting that stress in early childhood may be linked to gut disorders, but we wanted to delve deeply into the mechanisms and how these gut-brain connections work.”

Mouse Studies Show Lasting Effects of Early Childhood Stress

The research team investigated early childhood stress using mouse models as well as two large-scale studies involving children. In the animal study, newborn mice were separated from their mothers for several hours each day to simulate early stress. When examined months later (at an age corresponding to young adulthood), these mice exhibited increased anxiety-like behavior, abdominal pain, and problems with bowel movement. The nature of the motility problems differed by sex: females were more likely to develop diarrhea, while males were more likely to suffer from constipation.

Further experiments showed that different biological signaling pathways appear to control different symptoms. Interrupting signals from the sympathetic nervous system improved the motility problems but did not reduce the pain. In contrast, sex hormones influenced the pain but not the motility. Serotonin-related signaling pathways were involved in both the pain and bowel movement. “This suggests that there is no one-size-fits-all approach to treating disorders of gut-brain interaction and that, when patients exhibit different symptoms, we may need to target different signaling pathways,” said Margolis.

Human Studies Confirm Link Between Stress and Digestive Problems

The results from animal studies were confirmed by two large-scale human studies. One study followed more than 40,000 children in Denmark from birth to age 15. About half were born to mothers who suffered from untreated depression during or after pregnancy. Children of mothers with untreated depression had a higher risk of developing digestive complaints, including nausea and vomiting, functional constipation, colic, and irritable bowel syndrome. These findings build on earlier work showing that children of mothers who took antidepressants during pregnancy were more frequently diagnosed with functional constipation.” “The effects on children’s digestive systems appear to be even more severe when the mother’s depression remains untreated, suggesting that mothers suffering from depression should be treated during pregnancy. This may include non-pharmacological measures such as therapy, but some pregnant women may also require medication to treat their depression,” said Margolis. “This finding also reinforces our commitment to developing antidepressants that do not cross the placenta—a focus of many of our current studies.”

A second study analyzed data from nearly 12,000 children in the U.S. who participated in the NIH-funded “Adolescent Brain Cognitive Development” (ABCD) study. The researchers examined adverse childhood experiences such as abuse, neglect, and parental mental health issues and compared these with gastrointestinal symptoms at ages nine and ten. They found that any form of early childhood stress was associated with an increase in gastrointestinal problems. Interestingly, unlike the mouse studies, the human data showed no differences between males and females in terms of digestive symptoms. This suggests that early stress can similarly affect gut health and the gut-brain axis during critical developmental phases in both sexes.

Toward More Targeted Treatments for Gut Disorders

Overall, the research findings suggest that stress in early childhood can influence communication between the gut and the brain and contribute to long-term digestive problems such as pain and motility disorders. Motility can be either accelerated or slowed down, which contributes to typical symptoms such as diarrhea or constipation. The enteric nervous system, often referred to as the “gut brain,” can also be disrupted in its development, causing the signal transmission between the gut and the brain to become unbalanced in the long term. Additionally, studies show that stress in early life affects the immune system and can lead to increased susceptibility to inflammation. This can weaken the gut’s barrier function and further exacerbate symptoms. Another important factor is the gut microbiota, i.e., the totality of microorganisms living in the gut. It, too, is influenced by stress and can change in such a way that it sends negative signals to the brain or impairs gut function. Crucially, different biological mechanisms can lead to different symptom profiles. While increased pain sensitivity is the primary concern for some patients, motility disorders, immunological changes, or a disrupted microbiota dominate in others.

The realization that different biological signaling pathways trigger different symptoms could help develop more precise treatment approaches for disorders of gut-brain interaction. They suggest that functional gastrointestinal disorders should not be treated uniformly, but rather that individually tailored therapy is necessary. Depending on which mechanism is predominant, different measures may be appropriate, such as psychotherapeutic approaches for stress regulation, pharmacological treatments to influence bowel motility, or diet-based interventions to stabilize the microbiota. “When patients with gut problems come to us, we shouldn’t just ask them if they’re currently under stress; what happened in their childhood is also a very important question and something we need to take into account,” says Margolis. “This developmental history could ultimately help us better understand how certain disorders of gut-brain interaction develop and enable us to treat them based on specific mechanisms.”