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The study looks at how eating salt affects gut health in people with Crohn's disease. The aim of the study is to find out whether eating more salt increases the breakdown of proteins in the gut and if this makes inflammation and symptoms worse. By studying the link between salt, gut bacteria and inflammation, the study hopes to improve diet advice for people with Crohn's disease. This research may help find specific foods that affect the disease and lead to better, more personalized nutrition plans.
This longitudinal exploratory study has two related phases:
Phase 1 will enroll 300 Crohn's disease (CD) patients from McMaster's IBD and IBD Nutrition Clinics to assess dietary sodium intake and fecal proteolytic activity in relation to disease activity (active/inactive). Participants will be followed annually for 2 years, forming a registry. At baseline and each follow-up visit, data collected will include: demographics, BMI, CDAI, diet (1-week food recall via Keenoa and 6-month sodium questionnaire), blood (sodium, metabolomics, CRP), stool (microbiota, metabolomics, fecal calprotectin, proteolytic activity), and spot urine (sodium, potassium, creatinine, metabolomics). Extra visits will occur if a disease flare happens.
Phase 2 will involve 80 participants from Phase 1 (40 high-sodium diet [HSD], 40 low-sodium diet [LSD]), selected based on sodium intake. Over three visits (baseline, week 1, week 2), participants will provide fecal samples for microbiota and metabolomics analysis, and blood/urine samples (baseline and week 2). Colonoscopy with biopsies and video will be performed at week 2. Diet will be closely tracked using Keenoa to assess intake of sodium, carbs, UPF, fibre, and calories. After Phase 2, participants return to Phase 1 follow-up.
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| Measure | Description | Time Frame |
|---|---|---|
| Dietary Sodium Intake | Dietary sodium intake will be assessed via 24-hour dietary recall and sodium-specific food frequency questionnaires (mg/day). Values will be used to classify participants as HSD or LSD and correlated with changes in proteolytic activity, mucosal permeability, and disease activity. | Phase 1: baseline (Year 0); Year 1; and Year 2. Phase 2: baseline (Week 0); Week 1; and Week 2. |
| Measure | Description | Time Frame |
|---|---|---|
| Proteolytic Activity in Stool and Colonic Biopsies | Proteolytic activity will be assessed in fecal samples and colonic biopsies. Fecal samples will be analyzed for host and bacterial proteases (units of proteolytic activity per gram of stool, U/g), and colonic biopsies for host and bacterial proteases (units of proteolytic activity per mg of tissue, U/mg). Comparisons will be made between participants consuming a high-sodium diet (HSD) and a low-sodium diet (LSD) to evaluate associations with mucosal barrier dysfunction and disease activity over time. |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with a diagnosis of Crohn's disease followed at McMaster University's Gastroenterology Outpatient Clinic.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gaston H Rueda, MD | Contact | 905 521-2100 | 21875 | ruedag@mcmaster.ca |
| Name | Affiliation | Role |
|---|---|---|
| David Armstrong, MD | McMaster University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| McMaster University Medical Centre | Hamilton | Ontario | L8S 4L8 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38587201 | Background | Pang Z, Lu Y, Zhou G, Hui F, Xu L, Viau C, Spigelman AF, MacDonald PE, Wishart DS, Li S, Xia J. MetaboAnalyst 6.0: towards a unified platform for metabolomics data processing, analysis and interpretation. Nucleic Acids Res. 2024 Jul 5;52(W1):W398-W406. doi: 10.1093/nar/gkae253. | |
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It is not yet known if there will be a plan to make IPD available.
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| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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The following samples will be retained for analysis: blood (for sodium, CRP, and metabolomics), stool (for microbiota, metabolomics, fecal calprotectin, and proteolytic activity), and spot urine (for sodium, creatinine, potassium, and metabolomics). In Phase 2, additional fecal samples will be collected for microbiota and metabolomics analysis, along with blood and urine (for metabolomics), and colonic biopsies (for microbiota composition, metabolomics, proteolytic activity, and microbial proteases).
| Stool: Phase 1 - baseline (Year 0); Year 1; and Year 2. Biopsy: Phase 2 - Week 2 |
| Crohn's Disease Activity Index (CDAI) | Crohn's Disease Activity Index will be calculated using patient-reported symptoms, physical exam findings, and lab values (score, unitless). CDAI <150 indicates remission, 150-220 mild disease, 220-450 moderate disease, and >450 severe disease. CDAI scores will be compared between HSD and LSD groups to evaluate changes in clinical disease activity over time. | Phase 1: baseline (Year 0); Year 1; and Year 2. Phase 2: baseline (Week 0); and Week 2. |
| Mucosal Permeability | Colonic biopsies will be analyzed for mucosal barrier integrity using permeability assays (e.g., FITC-dextran flux). Higher values indicate greater barrier dysfunction (permeability index, arbitrary units). Comparisons will be made between HSD and LSD groups to determine effects of dietary sodium intake. | Phase 2: Week 2 |
| Patient Subgroup Characterization Based on Metabolic and Microbial Profiles | Participants will be characterized using dietary sodium intake, metabolic profiling (blood, urine, stool), and microbial activity (stool and biopsy-based proteolytic and microbiome analyses). Data will identify subgroups with distinct metabolic signatures, sodium intake levels, microbial profiles, and disease progression, providing insight into diet-microbiota-host metabolism interactions in Crohn's disease. | Phase 1: baseline (Year 0); Year 1; and Year 2. Phase 2: baseline (Week 0); Week 1; and Week 2. |
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| D007410 | Intestinal Diseases |