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Completed

NCT Number: NCT05249023

Mode of Action of Butyrate in the Human Colon

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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Key information

Conditions

Irritable Bowel Syndrome (IBS) Colonic Diseases Colonic Diseases, Functional Digestive System Diseases Gastrointestinal Diseases Healthy Intestinal Diseases Irritable Bowel Syndrome

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospital Örebro

Örebro, Örebro County, 70185, Sweden

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Primary outcomes

  1. Colonic permeability ex vivo in Ussing chambers

    Time frame: 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 outcomes

  1. Butyrate uptake ex vivo in Ussing chambers

    Time frame: 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

  2. Regulation of gene expression

    Time frame: 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

  3. Concentrations of blood glucagon like peptide-1 (GLP-1)

    Time frame: 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

  4. Concentrations of blood glucagon like peptide-2 (GLP-2)

    Time frame: 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

  5. Concentrations of blood peptide YY (PYY)

    Time frame: 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

  6. Concentrations of blood gastric inhibitory polypeptide (GIP)

    Time frame: 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

  7. Concentrations of blood insulin

    Time frame: 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

  8. Concentrations of blood glucagon

    Time frame: 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

  9. Concentrations of blood leptin

    Time frame: 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

  10. Concentrations of blood glucose

    Time frame: 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

  11. Concentrations of blood serotonin

    Time frame: 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

  12. Concentrations of blood metabolites in the gluconeogenic pathway

    Time frame: 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

  13. Concentrations of blood butyrate

    Time frame: 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

Other outcomes

  1. Gastrointestinal symptoms measured by Gastrointestinal Symptom Rating Scale-IBS

    Time frame: 1 week

    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).

  2. Food habits measured by an electronic food frequency questionnaire Mealq

    Time frame: 1 week

    Survey of participants food habits prior the exposure to the butyrate bolus.

Sponsors and collaborators

Lead sponsor

Örebro University, Sweden

Other

Registry information

Important dates

Study start
2018
Primary completion
2021
Study completion
2021
First posted
Feb 21, 2022
Registry last updated
Feb 21, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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