Mode of Action of Butyrate in the Human Colon

Not Applicable

Completed

• Conditions: Irritable Bowel Syndrome (IBS); Healthy
• Interventions: Other: Sodium butyrate bolus

• Registration Number: NCT05249023
• Lead Sponsor: Örebro University, Sweden

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-04-11
• Primary Completion: 2021-02-19
• Study Completion: 2021-02-19
• Study First Submitted: 2021-03-23
• Status Verified: 2022-02
• Study First Submitted QC: 2022-02-10
• Last Update Submitted: 2022-02-10
• Study First Posted: 2022-02-21
• Last Update Posted: 2022-02-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

• signed informed consent
• Fulfilled Rome IV diagnostic criteria for IBS (for IBS participants)

Exclusion Criteria

• known gastrointestinal diseases
• previous complicated gastrointestinal surgery (including e.g. appendectomy or cholecystectomy)
• pregnancy or breast-feeding
• use of antibiotics within the last 12 weeks before the colonoscopy procedure
• regular consumption of probiotics within the last 4 weeks before the colonoscopy procedure
• use of laxatives or anti-diarrhoeals within the last 4 weeks before the colonoscopy procedure
• use of serotonin selective re-uptake inhibitors (SSRI) or serotonin nor-epinephrine re-uptake inhibitors (SNRI) with the last 12 weeks before the colonoscopy procedure
• alcohol or drug abuse
• latex allergy
• any other clinically significant disease/condition which in the investigator's opinion could interfere with the results of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Irritable Bowel Syndrome (IBS) participants	Sodium butyrate bolus	100 mM sodium butyrate solution containing indigo carmine as a dye agent will be administered to subjects in this arm.
Healthy participants	Sodium butyrate bolus	100 mM sodium butyrate solution containing indigo carmine as a dye agent will be administered to subjects in this arm.

Primary Outcome Measures

Name	Time	Method
Colonic permeability ex vivo in Ussing chambers	Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution	Difference in the translocation of FITC-labeled dextran and horseradish peroxidase between the study arms before and after exposure to the butyrate bolus

Secondary Outcome Measures

Name	Time	Method
Concentrations of blood peptide YY (PYY)	Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).	Difference in blood levels of PYY between the study arms before and after exposure to the butyrate bolus
Regulation of gene expression	Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution	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
Concentrations of blood gastric inhibitory polypeptide (GIP)	Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).	Difference in blood levels of GIP between the study arms before and after exposure to the butyrate bolus
Concentrations of blood insulin	Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).	Difference in blood levels of insulin between the study arms before and after exposure to the butyrate bolus
Concentrations of blood serotonin	Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).	Difference in blood levels of serotonin between the study arms before and after exposure to the butyrate bolus
Butyrate uptake ex vivo in Ussing chambers	Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution	Difference in the uptake of C14-labelled butyrate between the study arms before and after exposure to the butyrate bolus
Concentrations of blood glucose	Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).	Difference in blood levels of glucose between the study arms before and after exposure to the butyrate bolus
Concentrations of blood metabolites in the gluconeogenic pathway	Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).	Difference in blood levels of metabolites in the gluconeogenic pathway between the study arms before and after exposure to the butyrate bolus
Concentrations of blood glucagon like peptide-1 (GLP-1)	Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).	Difference in blood levels of GLP-1 between the study arms before and after exposure to the butyrate bolus
Concentrations of blood glucagon like peptide-2 (GLP-2)	Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).	Difference in blood levels of GLP-2 between the study arms before and after exposure to the butyrate bolus
Concentrations of blood glucagon	Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).	Difference in blood levels of glucagon between the study arms before and after exposure to the butyrate bolus
Concentrations of blood leptin	Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).	Difference in blood levels of leptin between the study arms before and after exposure to the butyrate bolus
Concentrations of blood butyrate	Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).	Difference in blood levels of butyrate between the study arms before and after exposure to the butyrate bolus

Trial Locations

Locations (1)

University Hospital Örebro; 🇸🇪 Örebro, Örebro County, Sweden