High-Resolution Measurements of Diet-Microbiome Interactions
First-Principles Mapping of Regional Fermentation Physiology in the Human Intestine With Ingestible Capsules
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.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
Irritable Bowel Syndrome (IBS) affects an estimated 25-45 million people in the United States, accounts for roughly 20-40% of gastroenterology visits, and imposes a major societal burden, with annual U.S. costs estimated at approximately $1.7-$10 billion in direct medical spending and approximately $20 billion in indirect costs from lost productivity (Hulisz 2004; Leong et al. 2003; Canavan et al. 2014). Despite this burden, IBS remains poorly understood, and no validated biochemical diagnostic or curative therapy currently exists (Lacy et al. 2021; Kim et al. 2017).
In most individuals, a high-fiber diet supports a healthy microbiome and improves health outcomes without adverse symptoms (Fu et al. 2022). In patients with IBS, however, fermentable fiber is known to worsen symptoms such as bloating, flatulence, and abdominal pain; patients are often advised to restrict fermentable fiber intake (e.g., a low-FODMAP diet), and antibiotics are sometimes used therapeutically to suppress fermentation (Halmos et al. 2014; Lacy et al. 2021). These clinical observations motivate the mechanistic hypothesis underlying this protocol: that IBS symptoms may arise, at least in part, from disordered microbial fermentation and impaired intestinal gas handling.
Progress toward this goal has been limited by the absence of direct clinical tools capable of quantifying fermentation physiology in vivo and by intestinal region. Current clinical testing (e.g., hydrogen/methane breath testing) provides only an indirect, systemic proxy for fermentation and remains variably standardized (Rezaie et al. 2017; Pitcher et al. 2022).
The human intestine is more than 30 feet in length and is home to regionally distinct microbial communities that closely track local gut physiology (Martinez-Guryn et al. 2019). Recently developed non-invasive capsule-based microbiome sampling has shown that the small intestine and proximal colon harbor communities that are distinct from stool and disproportionately altered in IBS (Shalon et al. 2023; Leite et al. 2020; Chung et al. 2016).
This protocol leverages two complementary ingestible capsule technologies - a real-time gas-sensing capsule (Atmo) and a regional fluid/microbiome-sampling capsule (CapScan) - together with stool, urine, breath, and blood-based measurements, to establish regional gas production and consumption profiles in healthy individuals and patients with IBS.
The Healthy and IBS cohorts are defined by baseline clinical status and are not randomized. Within each cohort, participants undergo a randomized two-period crossover of meal order. Each participant receives both the low-fiber control meal and the 15 g inulin meal, with the order assigned at random.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Roujheen Sabetan, MPH
- Número de teléfono: 925-963-7021
- Correo electrónico: rsabetan@stanford.edu
Copia de seguridad de contactos de estudio
- Nombre: Jacob T Hizon, BS
- Número de teléfono: 619-874-4562
- Correo electrónico: jthizon@stanford.edu
Ubicaciones de estudio
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California
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Stanford, California, Estados Unidos, 94305
- Stanford University
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Contacto:
- Sean P Spencer, MD, PhD
- Número de teléfono: 608-469-5076
- Correo electrónico: seanspen@stanford.edu
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Age 18-75 years.
- Able to provide written informed consent.
- Able and willing to swallow capsules and complete all study procedures.
- For the Healthy cohort: no history of a diagnosed chronic GI disorder and no ongoing GI symptoms warranting clinical evaluation.
- 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.
- Willing and able to complete a virtual (Zoom) screening visit and two in-clinic study visits approximately one week apart.
Exclusion Criteria:
- Known or suspected gastrointestinal stricture or physiological/mechanical gastrointestinal obstruction.
- Gastrointestinal fistula.
- Dysphagia or other swallowing disorder affecting the ability to swallow food, pills, or capsules.
- Gastrointestinal surgery within the past 3 months.
- Prior gastrointestinal surgery that alters luminal anatomy (e.g., bowel resection or bariatric surgery).
- Diverticulitis.
- Gastric bezoar.
- Radiation enteritis.
- Pacemaker or other implanted or portable electromechanical medical device.
- Pregnancy or breastfeeding.
- BMI ≥40 kg/m².
- Use of antibiotics, probiotics, or prebiotics within 4 weeks prior to enrollment.
- Use of proton-pump inhibitors (e.g., omeprazole, lansoprazole, esomeprazole [Nexium®]) within 7 days prior to the study procedure.
- Use of histamine blockers, motility-altering medications, narcotic analgesics, or anticholinergic medications within 3 days prior to the study procedure.
- Use of antiemetics/5-HT3 antagonists, macrolide antibiotics, or 5-HT4-modulating medications within 2 days prior to the study procedure.
- Use of antacids (e.g., Gaviscon®, Mylanta®, TUMS) within 1 day prior to the study procedure.
- Diabetes or use of medications affecting glucose handling.
- Known allergy or intolerance to inulin or other study meal components.
- Current participation in another interventional study.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Healthy controls
The Healthy cohort consists of individuals without a diagnosed chronic gastrointestinal disorder or ongoing gastrointestinal symptoms warranting clinical evaluation. Participants complete two study visits approximately one week apart and receive both meal conditions in randomized order: low-fiber control followed by 15 g of inulin, or 15 g of inulin followed by low-fiber control. At each visit, participants consume the assigned standardized breakfast shake with the Atmo gas-sensing capsule at t=0 and ingest the CapScan regional sampling capsule at t=4 hours. |
Participants consume a standardized breakfast shake containing 15 g of inulin at one of the two study visits, according to the randomized meal sequence. At the other visit, they consume the same base shake without added inulin as the low-fiber control. Visits occur approximately one week apart. Participants consume the standardized low-fiber base breakfast shake without added inulin at one of the two study visits, according to the randomized meal sequence. This condition serves as the within-participant control. Visits occur approximately one week apart. At each of the two study visits, participants will swallow one Atmo gas-sensing capsule with the assigned standardized breakfast shake at t=0. As it transits the gastrointestinal tract, the wireless capsule records regional luminal hydrogen (H2), carbon dioxide (CO2), oxygen-related signals, temperature, and transit-related data. Data are transmitted by radiofrequency to a wearable receiver for analysis. Capsule passage will be monitored after each visit.
Otros nombres:
At each of the two study visits, participants will swallow one CapScan capsule at t=4 hours. CapScan is a single-use, passive ingestible device that collects regional gastrointestinal luminal fluid as it transits the intestine. The collected samples will be used for ex vivo microbiome and multiomic analyses. The device passes in the stool and is retrieved by the participant using the provided retrieval materials for subsequent processing.
Otros nombres:
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Experimental: Irritable Bowel Syndrome (IBS)
The IBS cohort consists of individuals who meet Rome IV diagnostic criteria for irritable bowel syndrome. Participants complete two study visits approximately one week apart and receive both meal conditions in randomized order: low-fiber control followed by 15 g of inulin, or 15 g of inulin followed by low-fiber control. At each visit, participants consume the assigned standardized breakfast shake with the Atmo gas-sensing capsule at t=0 and ingest the CapScan regional sampling capsule at t=4 hours. |
Participants consume a standardized breakfast shake containing 15 g of inulin at one of the two study visits, according to the randomized meal sequence. At the other visit, they consume the same base shake without added inulin as the low-fiber control. Visits occur approximately one week apart. Participants consume the standardized low-fiber base breakfast shake without added inulin at one of the two study visits, according to the randomized meal sequence. This condition serves as the within-participant control. Visits occur approximately one week apart. At each of the two study visits, participants will swallow one Atmo gas-sensing capsule with the assigned standardized breakfast shake at t=0. As it transits the gastrointestinal tract, the wireless capsule records regional luminal hydrogen (H2), carbon dioxide (CO2), oxygen-related signals, temperature, and transit-related data. Data are transmitted by radiofrequency to a wearable receiver for analysis. Capsule passage will be monitored after each visit.
Otros nombres:
At each of the two study visits, participants will swallow one CapScan capsule at t=4 hours. CapScan is a single-use, passive ingestible device that collects regional gastrointestinal luminal fluid as it transits the intestine. The collected samples will be used for ex vivo microbiome and multiomic analyses. The device passes in the stool and is retrieved by the participant using the provided retrieval materials for subsequent processing.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Successful Acquisition of a Complete Regional Multiomic Fermentation-Physiology Dataset
Periodo de tiempo: up to 12 months
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To successfully obtain a complete regional multiomic fermentation-physiology dataset - defined as paired Atmo gas capsule data (H2, CO2, O2), CapScan regional microbiome/fluid sampling, stool microbiome sequencing, and breath testing (H2, CH4, H2S) with serum SCFA measurements - from at least 30 of the 40 enrolled participants (15 healthy, 15 IBS), across both study visits. Primary outcome measure: the number and proportion of enrolled participants from whom a complete multiomic dataset is successfully obtained across both study visits. |
up to 12 months
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in Regional Intestinal Gas Concentrations Following Inulin Challenge
Periodo de tiempo: Through completion of both study visits, 2 week
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Regional hydrogen (H2), carbon dioxide (CO2), and oxygen (O2) concentration-time profiles will be measured using the Atmo gas-sensing capsule. Changes in gas concentrations between the low-fiber control visit and the 15 g inulin visit will be compared within participants and between healthy and IBS groups, including regional differences between the small intestine and colon. |
Through completion of both study visits, 2 week
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Regional Intestinal Microbiome Composition Following Dietary Fiber Challenge
Periodo de tiempo: Through completion of sample collection, up to 72 hours after each study visit
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Microbial composition will be characterized from regional intestinal fluid samples collected using the CapScan capsule and from stool samples. Microbiome profiles will be evaluated across intestinal regions and compared between the low-fiber and inulin visits and between healthy and IBS participants. |
Through completion of sample collection, up to 72 hours after each study visit
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Change in Breath H2, CH4, and H2S Concentrations Following Inulin Challenge
Periodo de tiempo: 8 hours during each study visit
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Breath hydrogen (H2), methane (CH4), and hydrogen sulfide (H2S) concentrations will be measured every 30 minutes during each 8-hour study visit. Concentration-time profiles will be compared between the low-fiber and inulin visits and between healthy and IBS participants. |
8 hours during each study visit
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Change in Serum Short-Chain Fatty Acid Concentrations Following Inulin Challenge
Periodo de tiempo: 8 hours during each study visit
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Serum short-chain fatty acid (SCFA) concentrations will be measured from serial blood samples collected every 30 minutes during each 8-hour study visit. SCFA concentration-time profiles will be compared between the low-fiber and inulin visits and between healthy and IBS participants. |
8 hours during each study visit
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Change in Gastrointestinal Symptom Severity Following Inulin Challenge
Periodo de tiempo: 8 hours during study visit
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Participant-reported gastrointestinal symptoms, including bloating/distention, abdominal pain/cramping, flatulence, nausea, and urgency, will be assessed throughout each study visit. Symptom trajectories will be compared between the low-fiber and inulin visits and between healthy and IBS participants. |
8 hours during study visit
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Glucose Response Following Dietary Fiber Challenge
Periodo de tiempo: Through CGM monitoring throughout 2 weeks including both study visits.
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Continuous glucose monitor (CGM)-derived glucose profiles will be evaluated following the low-fiber and inulin meal challenges. Glucose responses will be compared within participants across study visits and between healthy and IBS groups. |
Through CGM monitoring throughout 2 weeks including both study visits.
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Atmo Capsule Gastrointestinal Transit Time
Periodo de tiempo: From capsule ingestion through passage, confirmation up to 72 hours after clinic visit.
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Quantify the gastrointestinal transit time of the Atmo capsule after participant ingestion. |
From capsule ingestion through passage, confirmation up to 72 hours after clinic visit.
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Michael Fischbach, PhD, Stanford University
- Investigador principal: Sean P Spencer, MD PhD, Stanford University
- Director de estudio: Benjamin Good, PhD, Stanford University
- Director de estudio: Jonas Cremer, PhD, Stanford University
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades intestinales
- Enfermedades del Sistema Digestivo
- Enfermedades Gastrointestinales
- Enfermedades del Colon
- Enfermedades del Colon Funcionales
- Síndrome del intestino irritable
- Terapéutica
- Terapia con drogas
- Carbohidratos dietéticos
- Carbohidratos
- Polímeros
- Sustancias macromoleculares
- Polisacáridos
- Almidón
- Glucanos
- Biopolímeros
- Fructanos
- Sistemas de administración de medicamentos
- Inulina
Otros números de identificación del estudio
- 87591
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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