Mode of Action of Butyrate in the Human Colon

Healthy Clinical Trial

Official title:

Mode of Action of Butyrate in the Human Colon

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05249023
• Other study ID #: Bolus
• Status: Completed
• Phase: N/A
• Start date: April 11, 2018
• Est. completion date: February 19, 2021

Study information

• Verified date: February 2022
• Source: Örebro University, Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: February 19, 2021
• Est. primary completion date: February 19, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome (IBS)

Intervention

Other:
• Sodium butyrate bolus
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.

Locations

Country	Name	City	State
Sweden	University Hospital Örebro	Örebro	Örebro County

Sponsors (1)

Lead Sponsor	Collaborator
Örebro University, Sweden

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Food habits measured by an electronic food frequency questionnaire Mealq	Survey of participants food habits prior the exposure to the butyrate bolus.	1 week
Primary	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
Secondary	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
Secondary	Regulation of gene expression	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
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).