Childhood stress can cause digestive problems later in life

According to a new study published in the journal Nature, early life stress can lead to digestive problems later in life, caused by changes in the gut and sympathetic nervous system. Gastroenterology.

Our research shows that these stressors can have a real impact on a child’s development and lead to long-term gut problems. Understanding the mechanisms involved may help us create more targeted treatments.”

Cara Margolis, study author, director of the NYU Pain Research Center and professor of molecular pathology at the NYU College of Dentistry and pediatrics and cell biology, NYU Grossman School of Medicine

Emotional neglect and other adverse experiences early in life can have a profound impact on a child’s development. Research shows that early life stress, during pregnancy and after birth, can shape brain formation and is linked to a greater likelihood of developing mental health conditions like anxiety and depression.

Researchers at the Pain Research Center at NYU College of Dentistry sought to understand how these difficulties shape the brain’s two-way communication with the gut. When things go awry with this circulatory superhighway, people may experience digestive problems, including irritable bowel syndrome, stomach pain, and motility problems (e.g., constipation or diarrhea).

“When the brain is affected, the gut is also affected – both systems communicate 24 hours a day, seven days a week,” Margolis said. “Some data show that early life stress may be associated with gut disorders, but we wanted to take a deeper look at the mechanisms and how these gut-brain pathways work.”

The researchers explored early life stress in three different ways, using mouse models and two large studies of children.

In a study on rats, newborn rats were separated from their mothers for several hours a day, a model of early life stress. When researchers examined them several months later (the equivalent of young adulthood), the mice had higher levels of anxiety-like behaviors, gut pain and mobility problems. Changes in motility vary depending on gender, with female rats experiencing diarrhea and males experiencing constipation.

Additional experiments showed that different pathways can cause different gastrointestinal symptoms. Providing sympathetic signals to the gut resolved motility problems, but not pain, whereas sex hormones appeared to play a role in pain, but not motility. Serotonin-based pathways appear to influence both abdominal pain and motility.

“This suggests that there is no one-size-fits-all approach to treating disorders of gut-brain interaction, and when patients experience different symptoms, we may need to target different pathways,” Margolis said.

The association between early life stress and gastrointestinal issues found in preclinical experiments was largely mirrored in two large human studies. In one, researchers looked at a population-based study of more than 40,000 babies aged 15 to 15 in Denmark, half of whom were born to mothers with untreated depression during or after pregnancy.

They found that depression during and after pregnancy in mothers who did not take antidepressants was associated with an increased risk of children being diagnosed with several digestive disorders, including nausea and vomiting, functional constipation, colic, and irritable bowel syndrome. The findings build on a previous study led by Margolis that determined that children of mothers who took antidepressants during pregnancy were more likely to have functional constipation.

“The digestive consequences for children appear to be even more severe when maternal depression is left untreated, suggesting that mothers experiencing depression should be treated during pregnancy. This may include non-medical measures such as therapy, but some pregnant women may also need medications to treat their depression,” Margolis said. “This finding also strengthens our commitment to developing antidepressants that do not reach the placenta – which is the focus of many of our studies right now.”

In the second human study, researchers analyzed data from nearly 12,000 children in the US who were part of the NIH-funded Adolescent Brain Cognitive Development (ABCD) study. They looked at adverse childhood experiences, including abuse, neglect and parental mental health problems, and whether children had digestive problems at ages nine and 10. They found that any type of early childhood stress increased gastrointestinal symptoms.

In human studies, researchers did not find differences in digestive outcomes between men and women who experienced stress in early life, suggesting that difficulties during this critical developmental stage may impact gut and gut-brain health, regardless of gender.

Overall, studies suggest that early life stress may shape the development of gut-brain communication and contribute to long-term gastrointestinal symptoms, including pain and mobility issues. By demonstrating that different pathways regulate different symptoms, future studies can explore how to target different pathways to more effectively treat digestive issues such as disorders of gut-brain interaction.

“When patients come in with stomach problems, we shouldn’t just ask them if they’re stressed at the moment; what happened in your childhood is also a really important question and something we need to consider,” Margolis said. “This evolutionary history may ultimately inform how we understand how certain disorders of gut-brain interaction develop and how to treat them based on specific mechanisms.”