Mode of Action of Butyrate in the Human Colon

Örebro University, Sweden37 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Irritable Bowel Syndrome (IBS)Healthy

Sodium butyrate bolusOTHER

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

University Hospital Örebro

Örebro, Örebro County, Sweden

Outcomes

Primary Outcomes

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

Time frame: Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution

Secondary Outcomes

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

Time frame: Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution

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

Time frame: 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