Clinical trial NCT05249023: Mode of Action of Butyrate in the Human Colon
Official title: Mode of Action of Butyrate in the Human Colon
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome (IBS)
Healthy
Lead sponsor: Örebro University, Sweden
Sponsor class: OTHER
First posted: 2022-02-21
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Colonic permeability ex vivo in Ussing chambers
timeFrame: Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution
Secondary outcomes:
measure: Butyrate uptake ex vivo in Ussing chambers
timeFrame: Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution
measure: Regulation of gene expression
timeFrame: Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution
measure: Concentrations of blood glucagon like peptide-1 (GLP-1)
timeFrame: Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).
measure: Concentrations of blood glucagon like peptide-2 (GLP-2)
timeFrame: Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).
measure: Concentrations of blood peptide YY (PYY)
timeFrame: Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).
measure: Concentrations of blood gastric inhibitory polypeptide (GIP)
timeFrame: Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).
measure: Concentrations of blood insulin
timeFrame: Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).
measure: Concentrations of blood glucagon
timeFrame: Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).
measure: Concentrations of blood leptin
timeFrame: Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).
measure: Concentrations of blood glucose
timeFrame: Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).
measure: Concentrations of blood serotonin
timeFrame: Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).
measure: Concentrations of blood metabolites in the gluconeogenic pathway
timeFrame: Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).
measure: Concentrations of blood butyrate
timeFrame: Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).
Other outcomes:
measure: Gastrointestinal symptoms measured by Gastrointestinal Symptom Rating Scale-IBS
timeFrame: 1 week
measure: Food habits measured by an electronic food frequency questionnaire Mealq
timeFrame: 1 week
Locations:
city: Örebro
country: Sweden
facility: University Hospital Örebro
state: Örebro County
Study officials:
References: