$4 Million NIH Grant Targets Lingering Gut Symptoms When Colitis Inflammation Fades

Researchers at UCLA Health and the Icahn School of Medicine at Mount Sinai have received a $4 million grant from the National Institutes of Health to tackle one of the most frustrating puzzles in gastroenterology: why many patients with ulcerative colitis continue to suffer from irritable bowel syndrome-like symptoms even after the visible inflammation in their intestines has largely resolved. The five-year study, announced by the University of California, Los Angeles, will be led jointly by gastroenterologist Lin Chang of UCLA Health and Dr. Bruce Sands, chief of the gastroenterology division at Mount Sinai, who will serve as co-principal investigators. The project is scheduled to conclude in June 2031.

Ulcerative colitis is a chronic inflammatory bowel disease that causes long-standing inflammation and ulceration of the inner lining of the large intestine and rectum. Patients typically experience abdominal cramping, bloating, diarrhea and irregular bowel movements, symptoms that can significantly impair quality of life. Modern therapies, including corticosteroids, immunomodulators and biologic agents, have become remarkably effective at suppressing the underlying inflammation, and many patients achieve what clinicians call remission. Yet a substantial fraction of these patients do not feel well even when their colonoscopies and biopsies suggest their disease is quiet.

The central question of the new study is deceptively simple: are these lingering symptoms a sign of disease activity that standard testing misses, or are they driven by an entirely different mechanism? The answer matters enormously for patients. If persistent symptoms reflect ongoing, subclinical inflammation, treatment should be intensified. If instead they arise from altered gut-brain signaling, escalating immunosuppressive therapy may expose patients to risks without any benefit, and approaches that target the nervous system may be more appropriate.

The scale of the problem is considerable. According to the source announcement, in roughly one in three patients with ulcerative colitis, symptoms resembling those of irritable bowel syndrome persist even when inflammation is minimal or absent. Irritable bowel syndrome is a functional gastrointestinal disorder, distinct from inflammatory bowel disease, in which symptoms occur without the tissue damage and inflammation characteristic of colitis. The overlap between the two conditions has long complicated clinical decision-making, because the same complaint, diarrhea or abdominal pain, can signal very different underlying processes depending on the patient.

Chang, who is vice chief of the Vatche and Tamar Manoukian Division of Digestive Diseases at UCLA, brings to the project an unusually broad portfolio of leadership roles that reflect the interdisciplinary nature of the research. She directs the Walter and Shirley Wang Center for Integrative Digestive Health, co-directs the G. Oppenheimer Center for Neurobiology of Stress and Resilience, directs the Clinical Studies and Database Core of the Goodman-Luskin Microbiome Center and serves as program director of the UCLA Gastroenterology Fellowship Program. Her co-investigator, Sands, leads the gastroenterology division at Mount Sinai, one of the country’s major centers for inflammatory bowel disease care and research.

Methodologically, the study is designed to interrogate both sides of the gut-brain axis, the bidirectional communication network linking the enteric nervous system of the digestive tract with the central nervous system. The researchers will deploy brain imaging to examine how the brains of patients with quiescent colitis and persistent symptoms differ in their processing of visceral signals, an approach that has previously revealed altered pain and arousal networks in functional gastrointestinal disorders. In parallel, participants will wear wearable technology capable of measuring autonomic nervous system function, providing continuous, real-world data on heart rate variability and other physiological markers that reflect the balance between sympathetic and parasympathetic activity.

The autonomic nervous system is a plausible culprit in this context. It regulates gut motility, secretion and sensitivity, and disruptions in its signaling have been implicated in both inflammatory bowel disease and irritable bowel syndrome. Chronic inflammation can remodel autonomic pathways, and conversely, altered autonomic tone can influence immune activity in the gut. By capturing these measurements longitudinally in patients whose inflammation has subsided, the team hopes to determine whether persistent symptoms correlate with measurable autonomic dysfunction, with residual inflammatory activity, or with some interaction between the two.

Perhaps the most clinically ambitious component of the study is its test of a potential intervention. The researchers will evaluate whether non-invasive vagal nerve stimulation can improve symptoms in affected patients. Vagal nerve stimulation, which delivers electrical impulses to the vagus nerve, the main conduit of parasympathetic signaling between the brain and the body, has been used for years in neurology and is increasingly explored for disorders involving gut-brain dysregulation. Because the vagus nerve modulates both immune responses and visceral sensory processing, stimulating it could in principle address the mechanisms the study is designed to uncover, offering a therapy that works through the nervous system rather than the immune system.

The ultimate goal, according to the announcement, is to support new personalized treatment approaches for ulcerative colitis patients who have little to no active inflammation yet continue to experience persistent IBS-like symptoms. Personalization is the key word. If the study succeeds in distinguishing symptom drivers at the level of individual patients, clinicians could one day match therapies to mechanisms, reserving anti-inflammatory escalation for those with hidden inflammation and offering neuromodulation or related approaches to those whose symptoms stem from altered gut-brain signaling. That would represent a meaningful shift in how gastroenterologists manage the growing population of patients in inflammatory bowel disease remission who still do not feel well.

The grant also reflects a broader trend in digestive disease research, in which the traditional boundary between organic and functional disorders is dissolving. Conditions once dismissed as purely psychological are now understood to involve measurable alterations in neural signaling, immune activity and the microbial environment of the gut. By combining neuroimaging, wearable physiology and a neuromodulation trial within a single five-year program, the UCLA and Mount Sinai team is positioned to generate exactly the kind of mechanistic evidence that could move persistent post-inflammatory symptoms from the margins of gastroenterology into the mainstream of precision medicine. For the roughly one in three patients whose colitis has quieted but whose symptoms have not, the study offers the prospect that their suffering will finally be explained, and treated, on its own terms.

Subject of Research: Persistent IBS-like symptoms in ulcerative colitis patients with resolved inflammation and gut-brain signaling mechanisms

Article Title: UCLA Health awarded $4 million NIH grant to study why ulcerative colitis symptoms persist after inflammation subsides

Article References: UCLA Health awarded $4 million NIH grant to study why ulcerative colitis symptoms persist after inflammation subsides. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: ulcerative colitis, irritable bowel syndrome, gut-brain axis, NIH grant, UCLA Health, Mount Sinai, vagal nerve stimulation, autonomic nervous system, brain imaging, inflammatory bowel disease, gastroenterology, Lin Chang