Early life stress may program the gut–brain axis for lifelong digestive problems

New research suggests that what happens in the earliest stages of life can leave a lasting mark on the gut–brain connection, increasing the risk of digestive problems years later. Stress during pregnancy, infancy, and childhood appears to alter how the nervous system and the digestive tract communicate, potentially setting the stage for conditions such as chronic abdominal pain, irritable bowel syndrome, constipation, and diarrhea.

A series of animal and human studies, published in the journal Gastroenterology, connects early psychological stress with measurable changes in both the gut and the sympathetic nervous system. The findings point toward more personalized approaches for treating disorders that arise from disrupted communication between the brain and the digestive system.

How early stress shapes brain–gut development

Emotional neglect, abuse, and other early adversities are known to influence how a child’s brain develops and to raise the risk of anxiety and depression later in life. The new work from NYU College of Dentistry’s Pain Research Center extends this understanding to the digestive system by focusing on the brain–gut axis, the bidirectional communication network that coordinates digestion and pain signaling.

Researchers highlight that the brain and gut are in constant dialogue via nerves, hormones, and immune pathways. When stress disrupts this system during sensitive periods of development, it may alter how signals are processed and how the gut functions. Such disruptions are linked to disorders of gut–brain interaction, including irritable bowel syndrome, functional abdominal pain, and motility problems such as constipation and diarrhea.

Mouse research reveals lasting impacts of early stress

To probe causation and underlying mechanisms, the team used mouse models that mimic early life stress. Newborn mice were separated from their mothers for several hours each day, a well-established experimental model for early adversity.

When these mice were examined months later—roughly corresponding to young adulthood in humans—they showed several persistent changes:

• Increased anxiety-like behaviors
• Heightened sensitivity to gut pain
• Altered gut motility, resulting in either constipation or diarrhea

Interestingly, motility problems differed by sex: females were more prone to diarrhea, while males tended to develop constipation. This suggested that sex-specific biological factors might shape how stress affects the digestive system.

Further experiments identified distinct biological routes for different symptoms:

• Sympathetic nervous system signaling played a key role in motility changes. When researchers disrupted this signaling, bowel movement problems improved, but pain did not.
• Sex hormones were more closely tied to pain responses and had less influence on motility.
• Serotonin pathways were involved in both pain sensitivity and gut movement, pointing to a shared mechanism across symptoms.

These findings indicate that no single pathway explains all outcomes of early stress. Instead, pain, motility, and other digestive symptoms may emerge from partially distinct biological processes, which has implications for how these conditions should be treated.

Large human studies confirm links between stress and gut disorders

To see whether the animal data reflected patterns in people, the researchers analyzed two large human datasets, one from Denmark and one from the United States.

Danish study: maternal depression and childhood digestive problems

The first study tracked more than 40,000 children in Denmark from birth to age 15. About half were born to mothers who experienced depression during or shortly after pregnancy and did not receive treatment.

Children whose mothers had untreated depression had a higher risk of several digestive conditions, including:

• Functional constipation
• Nausea and vomiting
• Infant colic
• Irritable bowel syndrome

These results build on earlier findings that children exposed to antidepressant medications in the womb had an elevated likelihood of functional constipation. Together, the data suggest that both maternal depression itself and its treatment can influence a child’s digestive health.

The authors note that outcomes appeared worse when maternal depression went untreated, underscoring the importance of addressing mental health during pregnancy. They point out that treatment may involve non-drug options such as psychotherapy, while some women may also need medication. The results also support ongoing efforts to develop antidepressants that do not cross the placenta.

US study: adverse childhood experiences and gut symptoms

In a second analysis, researchers used data from nearly 12,000 children participating in the NIH-funded Adolescent Brain Cognitive Development (ABCD) study in the United States. This project collects detailed information on children’s environments, mental health, and physical health.

The team examined adverse childhood experiences such as abuse, neglect, and parental mental health difficulties, and compared these with gastrointestinal symptoms reported at ages nine and ten. Any form of early stress was associated with an increased burden of digestive complaints.

Unlike in the mouse model, however, the human data did not show clear differences between boys and girls in digestive outcomes at this age. This suggests that, during certain developmental windows, early stress may affect gut and gut–brain function in a broadly similar way across sexes, at least for the types of symptoms captured in this cohort.

Toward more targeted prevention and treatment

Across both animal and human data, a consistent picture emerges: stress in early life can alter how the gut and brain communicate, increasing the likelihood of chronic digestive problems later on. The work also indicates that different biological systems—such as the sympathetic nervous system, sex hormones, and serotonin pathways—contribute differently to pain and motility issues.

This mechanistic insight may help clinicians move toward more tailored therapies for disorders of gut–brain interaction. Rather than relying on a single approach for all patients, treatment could eventually be guided by dominant symptoms and the pathways thought to be driving them.

The findings also highlight the importance of taking a thorough developmental and psychosocial history when people present with chronic gut complaints. Questions about stress during pregnancy, early caregiving experiences, and childhood adversity may offer valuable clues to how and why certain digestive disorders emerged.

By linking early experiences to specific biological changes in the gut–brain axis, the study supports a more integrated view of digestive health—one that includes both mental and physical factors from the very start of life.