When Stress Is a Gut Punch: New Research Reveals How Stress Slows Digestion
Study Traces How Stress Hormones Disrupt the Gut — Points to New Target for Treating IBS
BOSTON — We’ve all experienced it: stress affects every system in the body, including — sometimes especially including — the gut. The stomach tightens. Digestion slows. Processes that usually run quietly in the background begin clamoring for attention. For some people, these symptoms resolve quickly. For others — particularly people with constipation-predominant irritable bowel syndrome (IBS-C) and related conditions — they don’t.
In a new study published in the Journal of Biological Chemistry, investigators at Beth Israel Deaconess Medical Center (BIDMC) identify the biological mechanism behind it. Led by corresponding author Subhash Kulkarni, PhD, principal investigator in the Division of Gastroenterology at BIDMC, the research shows how stress hormones directly interfere with gut function, slowing digestion through a newly defined pathway, and pointing toward a potential way to treat stress-associated constipation.
“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 postdoctoral fellow Srinivas N. Puttapaka, who lead the study with co-lead author Jared Slosberg, a doctoral candidate at Johns Hopkins University School of Medicine.
Kulkarni and colleagues’ work centers on the enteric nervous system (ENS), often called the “second brain” of the gastrointestinal tract. This network of nerves in the gut controls how food moves through the digestive system, and can coordinate digestion on its own, without input from the brain or spinal cord. However, the ENS is connected to the rest of the nervous system and does receive signals from the outside world, meaning the stressors big and small can override its normal functions.
Scientists already knew that stress hormones can disrupt ENS signaling and had demonstrated a disrupted signaling pathway in patients with irritable bowel syndrome (IBS). What was not clear was exactly how that disruption happens or whether it could be reversed. In the new study, the researchers show exactly how stress interferes with the pathway and demonstrate that restoring it improves gut function in preclinical models, identifying it as a promising target for new IBS treatments.
Specifically, Kulkarni and colleagues found that stress hormones suppress the gut’s cell-to-cell communication, leaving GI movement slowed and increasing the risk of persistent constipation. The team traced this breakdown to a specific chemical signaling pathway in the gut — involving a molecule called BDNF and its receptor, TrkB — that helps keep digestion responsive.
When the researchers activated this pathway using a compound that stimulates the TrkB receptor, they were able to restore normal gut movement in experimental models of stress.
“Together, this identifies that TrkB is an important therapeutic target for the amelioration of GI dysmotility in patients with disorders of gut–brain interaction such as IBS-C,” Kulkarni said.
“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.
Co-authors included Philippa Seika, Su Min Hong, Ainsleigh Scott, Srinivas N. Puttapaka, and Subhash Kulkarni of Beth Israel Deaconess Medical Center and Harvard Medical School; Jared Slosberg of Johns Hopkins University School of Medicine; Alpana Singh and Anthony Lembo of Cleveland Clinic; and Gamze Sonmez of Hacettepe University.
This work was funded by the National Institute on Aging (grants R01AG066768 and R21AG072107); the Diacomp Foundation (Pilot award Augusta University); a Pilot grant from the Harvard Digestive Disease Core to Subhash Kulkarni; the Walter Benjamin Fellowship (528835020) from the Deutsche Forschungsgemeinschaft to Philippa Seika; and additional support from Harvard Catalyst and the National Institutes of Health. The authors disclose no conflicts of interest.
About Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center is a leading academic medical center, where extraordinary care is supported by high-quality education and research. BIDMC is a teaching affiliate of Harvard Medical School, and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is the official hospital of the Boston Red Sox.
Beth Israel Deaconess Medical Center is a part of Beth Israel Lahey Health, a healthcare system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,700 physicians and 39,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.
