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Butyrate has recently gained attention as an important microbial compound in human colon health. Several diseases, including Irritable Bowel Syndrome (IBS), have been linked with a loss of butyrate in the colon resulting in the hypothesis that butyrate is important for disease resistance. However, despite a plethora of preclinical evidence about butyrate's role in colon health, data from human studies are insufficient, largely due to the lack of available tools for colon-specific butyrate delivery and sampling. This project will elucidate butyrate's mode of action in the human colon and its implications for gut functioning in IBS and healthy participants by employing a unique in vivo human setting. Specifically, the regulatory capacity of butyrate on intestinal barrier function and the transcriptional host responses that are associated with an increase of butyrate in the colon will be determined. Moreover, butyrate's role as a signalling molecule for gut hormones and serotonin release will be studied.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Irritable Bowel Syndrome (IBS) participants | Experimental | 100 mM sodium butyrate solution containing indigo carmine as a dye agent will be administered to subjects in this arm. |
|
| Healthy participants | Experimental | 100 mM sodium butyrate solution containing indigo carmine as a dye agent will be administered to subjects in this arm. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sodium butyrate bolus | Other | On the test day participants suffering from IBS and healthy participants will undergo a distal colonoscopy procedure for the collection of mucosal biopsy specimens pre- and post-administration of a sodium butyrate solution (100 mM) at a selected area in the descending colon. Biopsies will be obtained from the colon pre- and 90 min post-administration of the intervention solution. Blood samples will be collected before and at six time-points after the intervention solution administration. |
| Measure | Description | Time Frame |
|---|---|---|
| Colonic permeability ex vivo in Ussing chambers | Difference in the translocation of FITC-labeled dextran and horseradish peroxidase between the study arms before and after exposure to the butyrate bolus | Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution |
| Measure | Description | Time Frame |
|---|---|---|
| Butyrate uptake ex vivo in Ussing chambers | Difference in the uptake of C14-labelled butyrate between the study arms before and after exposure to the butyrate bolus | Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution |
| Regulation of gene expression |
| Measure | Description | Time Frame |
|---|---|---|
| Gastrointestinal symptoms measured by Gastrointestinal Symptom Rating Scale-IBS | Difference in the frequency and severity of gastrointestinal symptoms between the study arms before and after the exposure to the butyrate bolus (13 items that measure the severity of IBS symptoms in five clusters (pain, bloating, constipation, diarrhea, and early satiety). | 1 week |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Örebro | Örebro | Örebro County | 70185 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40810534 | Derived | Scharf MW, Forsgard RA, Prado SBR, Ganda Mall JP, Repsilber D, Brummer RJ, Marques TM, Wall R. Acute effects of butyrate on intestinal permeability in patients with irritable bowel syndrome assessed by a novel colonoscopy research model. Gut Microbes. 2025 Dec;17(1):2545414. doi: 10.1080/19490976.2025.2545414. Epub 2025 Aug 14. |
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| ID | Term |
|---|---|
| D043183 | Irritable Bowel Syndrome |
| ID | Term |
|---|---|
| D003109 | Colonic Diseases, Functional |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
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|
Difference in the genome-wide transcriptional response to an increase of butyrate in the descending colon between the study arms before and after exposure to the butyrate bolus |
| Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution |
| Concentrations of blood glucagon like peptide-1 (GLP-1) | Difference in blood levels of GLP-1 between the study arms before and after exposure to the butyrate bolus | Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min). |
| Concentrations of blood glucagon like peptide-2 (GLP-2) | Difference in blood levels of GLP-2 between the study arms before and after exposure to the butyrate bolus | Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min). |
| Concentrations of blood peptide YY (PYY) | Difference in blood levels of PYY between the study arms before and after exposure to the butyrate bolus | Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min). |
| Concentrations of blood gastric inhibitory polypeptide (GIP) | Difference in blood levels of GIP between the study arms before and after exposure to the butyrate bolus | Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min). |
| Concentrations of blood insulin | Difference in blood levels of insulin between the study arms before and after exposure to the butyrate bolus | Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min). |
| Concentrations of blood glucagon | Difference in blood levels of glucagon between the study arms before and after exposure to the butyrate bolus | Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min). |
| Concentrations of blood leptin | Difference in blood levels of leptin between the study arms before and after exposure to the butyrate bolus | Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min). |
| Concentrations of blood glucose | Difference in blood levels of glucose between the study arms before and after exposure to the butyrate bolus | Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min). |
| Concentrations of blood serotonin | Difference in blood levels of serotonin between the study arms before and after exposure to the butyrate bolus | Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min). |
| Concentrations of blood metabolites in the gluconeogenic pathway | Difference in blood levels of metabolites in the gluconeogenic pathway between the study arms before and after exposure to the butyrate bolus | Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min). |
| Concentrations of blood butyrate | Difference in blood levels of butyrate between the study arms before and after exposure to the butyrate bolus | Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min). |
| Food habits measured by an electronic food frequency questionnaire Mealq | Survey of participants food habits prior the exposure to the butyrate bolus. | 1 week |
| D004066 | Digestive System Diseases |