Adaptive Mechanism-Based Intervention for Persistent Somatic Symptoms: An Experimental Randomised Controlled Trial in Patients with Irritable Bowel Syndrome and Ulcerative Colitis (SOMA.GUT.2)

• Applicants: Professor Dr. Samuel Huber; Professor Dr. Bernd Löwe
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine ; Gastroenterology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445297796

Background: Irritable bowel syndrome (IBS) and ulcerative colitis (UC) are chronic conditions, affecting approximately 4% and 0.3% of the global population, respectively. Despite distinct pathophysiology, both are characterised by persistent gastrointestinal (GI) symptoms such as abdominal pain, altered bowel habits, and changes in the intestinal microbiota. Effective options for symptom control are limited. Biopsychosocial models developed within SOMACROSS highlight modifiable psychological factors—particularly dysfunctional symptom expectations and illness-related anxiety—as drivers of symptom persistence. Results of first funding phase (FP1): In the three-arm SOMA.GUT trial, a mechanism-based intervention, added to standard care (SC), targeting these factors improved illness-related anxiety and dysfunctional expectations after 3 months, with delayed benefits on GI symptom severity after 12 months and preliminary indications of microbiota changes. Objectives: SOMA.GUT.2 will refine the intervention regarding targeting, dosage, and personalisation. The programme comprises four-session, therapist-guided online modules derived from FP1: SOMA.EXPECT (dysfunctional expectations), SOMA.SYMP (symptom-related distress), and SOMA.COPE (depression). We hypothesise that in IBS and UC, the personalised mechanism-based intervention plus SC (GUT.ADAPT + SC) will be superior to SC alone in reducing GI symptom severity after 6 months. We further expect changes in the targeted mechanisms, microbiome shifts, and evidence from patient-specific gnotobiotic mouse models indicating that these shifts partly mediate clinical benefits. Work programme: The two-arm randomised controlled SOMA.GUT.2 trial will recruit 160 patients with physician-confirmed IBS or UC, randomised 1:1 to intervention versus control. All participants in the intervention group will start with SOMA.EXPECT; SOMA.SYMP and/or SOMA.COPE will be added if symptoms persist. The primary outcome is GI symptom severity (IBS-SSS) after 6 months. Secondary outcomes include changes in the targeted mechanisms and microbiota composition. Longitudinal mediation models will test mechanistic pathways. In a subgroup, ecological momentary assessment and wearable data will capture short-term dynamics between symptoms, mechanisms, and autonomic signals. Faecal samples from responders and non-responders will be transplanted into germ-free mice to generate patient-specific gnotobiotic models for colitis experiments and behavioural testing. Expected impact: SOMA.GUT.2 will yield robust evidence on mechanisms of persistent GI symptoms. By integrating clinical research, digital monitoring, microbiome analyses, and gnotobiotic models, findings will inform the development of more effective, targeted treatments for persistent GI symptoms in IBS and UC. The parallel study of both disorders will distinguish disorder-specific from transdiagnostic mechanisms and foster targeted and personalised care.

• DFG Programme: Research Units
• Subproject of: FOR 5211: Persistent SOMAtic Symptoms ACROSS Diseases: From Risk Factors to Modification (SOMACROSS.2)
• International Connection: Belgium, Netherlands
• Cooperation Partners: Professor Omer van den Bergh, Ph.D.; Professorin Dr. Judith Rosmalen