Researchers at Beth Israel Deaconess Medical Center reported on May 19 that stress hormones can directly interfere with gut function by slowing digestion through a newly defined pathway. The findings, published in the Journal of Biological Chemistry, suggest a potential approach for treating stress-associated constipation.
The study is significant because it clarifies how psychological stress can impact digestive health, particularly for people with constipation-predominant irritable bowel syndrome and related conditions. For some individuals, digestive symptoms caused by stress resolve quickly, but for others they persist and cause ongoing discomfort.
The research was led by Subhash Kulkarni, assistant professor of medicine at Harvard Medical School and principal investigator in the Division of Gastroenterology at Beth Israel Deaconess. The team focused on the enteric nervous system (ENS), known as the “second brain” of the gastrointestinal tract. This network controls food movement through the digestive system and usually operates independently from the brain or spinal cord but is still influenced by external signals such as stress.
Scientists previously understood that stress hormones could disrupt ENS signaling and had seen this effect in patients with irritable bowel syndrome. However, it was unclear exactly how this disruption occurred or if it could be reversed. In their new work, Kulkarni’s group demonstrated that stress hormones suppress cell-to-cell communication in the gut via a specific chemical pathway involving a molecule called BDNF and its receptor TrkB. When this pathway was activated using a compound to stimulate TrkB receptors in experimental models under stress, normal gut movement was restored.
“This study identifies both the basic biology for why stress slows down your gut and creates a platform through which novel therapeutics can be generated and tested for treating stress-associated constipation,” said Srinivas N. Puttapaka, an HMS research fellow who co-led the study with Jared Slosberg from Johns Hopkins University School of Medicine.
“By pinpointing how stress disrupts this pathway and showing that its function can be restored, we’ve identified a clear and actionable target for developing new treatments for IBS,” said Puttapaka.
The work received funding from several sources including the National Institute on Aging; Harvard Digestive Disease Core; Deutsche Forschungsgemeinschaft; Diacomp Foundation; Harvard Catalyst; and National Institutes of Health.
