High-Resolution Measurements of Diet-Microbiome Interactions

The goal of this clinical trial is to characterize regional intestinal fermentation physiology and determine how the response to fermentable dietary fiber differs between healthy individuals and individuals with irritable bowel syndrome (IBS). The study will use ingestible capsule technologies to directly measure intestinal gases and regional microbiome composition following low-fiber and high-fiber meal challenges. The main questions it aims to answer are: Does the change in regional intestinal gas levels following a fermentable-fiber challenge differ between participants with IBS and healthy controls? How are regional intestinal gas dynamics associated with microbiome composition, breath gases, serum short-chain fatty acids, glucose dynamics, metabolites, and gastrointestinal symptoms? Researchers will compare participants with IBS to healthy controls to determine whether intestinal fermentation responses to dietary fiber differ between these populations. Participants will: Complete two study visits approximately one week apart. At one visit, participants will receive a low-fiber control meal, and at the other visit, they will receive the same base meal containing 15 g of inulin. The order of the two meals will be assigned at random. Swallow an Atmo gas-sensing capsule to measure intestinal H2, CO2, and O2 and a CapScan capsule to collect regional intestinal fluid for microbiome analysis. Undergo serial blood and breath sampling and gastrointestinal symptom assessments during each 8-hour study visit. Complete stool and urine collections, dietary assessment, and continuous glucose monitoring before and/or after the study visits.

Inclusion Criteria: 1. Age 18-75 years. 2. Able to provide written informed consent. 3. Able and willing to swallow capsules and complete all study procedures. 4. For the Healthy cohort: no history of a diagnosed chronic GI disorder and no ongoing GI symptoms warranting clinical evaluation. 5. For the IBS cohort: meets Rome IV diagnostic criteria for IBS, with a prior clinical hydrogen/methane breath test on record sufficient to assign a breath-test subtype. 6. Willing and able to complete a virtual (Zoom) screening visit and two in-clinic study visits approximately one week apart. Exclusion Criteria: 1. Known or suspected gastrointestinal stricture or physiological/mechanical gastrointestinal obstruction. 2. Gastrointestinal fistula. 3. Dysphagia or other swallowing disorder affecting the ability to swallow food, pills, or capsules. 4. Gastrointestinal surgery within the past 3 months. 5. Prior gastrointestinal surgery that alters luminal anatomy (e.g., bowel resection or bariatric surgery). 6. Diverticulitis. 7. Gastric bezoar. 8. Radiation enteritis. 9. Pacemaker or other implanted or portable electromechanical medical device. 10. Pregnancy or breastfeeding. 11. BMI ≥40 kg/m². 12. Use of antibiotics, probiotics, or prebiotics within 4 weeks prior to enrollment. 13. Use of proton-pump inhibitors (e.g., omeprazole, lansoprazole, esomeprazole \[Nexium®\]) within 7 days prior to the study procedure. 14. Use of histamine blockers, motility-altering medications, narcotic analgesics, or anticholinergic medications within 3 days prior to the study procedure. 15. Use of antiemetics/5-HT3 antagonists, macrolide antibiotics, or 5-HT4-modulating medications within 2 days prior to the study procedure. 16. Use of antacids (e.g., Gaviscon®, Mylanta®, TUMS) within 1 day prior to the study procedure. 17. Diabetes or use of medications affecting glucose handling. 18. Known allergy or intolerance to inulin or other study meal components. 19. Current participation in another interventional study.