Influence of Bile Acids on Bacterial Uptake in Functional Dyspepsia

Translocation of Microorganisms in Duodenal Biopsies of Healthy Volunteers and Patients With Functional Dyspepsia

In up to half of patients seen by gastroenterologists, routine examinations fail to find an underlying organic, systemic, or metabolic disease that readily explains the symptoms. These patients are referred to as patients with disorders of gastrointestinal function, of which functional dyspepsia (FD) is one of the most common. Despite intensive research to investigate various pathophysiological mechanisms of this disease, the pathogenesis remains obscure. The investigators recently demonstrated increased duodenal permeability in FD patients, as assessed by mounting routine endoscopic duodenal biopsy specimens into Ussing chambers to measure transepithelial electrical resistance and passage of a paracellular fluorescent probe. Impaired intestinal barrier function can lead to increased uptake of luminal substances which can induce an immunological response in the mucosa. Interestingly, using transmission electron microscopy (TEM) in duodenal biopsies, the investigators recently observed the presence of a yet to be identified microorganism inside the epithelium and the lamina propria of a subset of FD patients (unpublished observations), suggesting increased translocation of microorganisms.

The aim of the project is to investigate whether FD patients display increased translocation of microorganisms in duodenal biopsies. The investigators will also test the effect of bile acid on translocation of microorganisms and therefore include 20 FD patients and 20 age- and gender-matched healthy volunteers in this study.

Study Overview

• Status: Completed
• Conditions: Functional Dyspepsia
• Intervention / Treatment: Procedure: Gastroduodenoscopy

Detailed Description

The participants will be expected on the department endoscopy of the University Hospital Gasthuisberg, Leuven, Belgium. They are asked to fill in a bundle of questionnaires concerning physical complaints, depression, anxiety (disturbances), pain/disease, body/interoceptive awareness, trauma/abuse and personality. Endoscopy will be performed and up to 8 biopsies will be obtained from the duodenum. All endoscopies will be performed by an experienced endoscopist. Biopsies will be mounted in Ussing chambers and the mucosal compartment will be exposed to commercially available fluorescein-conjugated microorganisms. Uptake of microorganisms will be evaluated by analyzing the serosal compartment and by confocal microscopy of the biopsies. These experiments will also be performed in combination with exposure to bile acids separately and jointly, to assess if bacterial translocation can be exacerbated by these endogenous luminal factors individually and synergistically.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Translational Research center for Gastrointestinal Disorders (TARGID)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Three days before the measurement: no smoking and drinking alcohol
• 12 hours before the measurement: no drinking and eating

Exclusion Criteria:

• symptoms or history of gastrointestinal disease
• first degree relatives with celiac disease
• diabetes mellitus
• allergy/atopy (eczema, asthma, allergic rhinoconjunctivitis)
• coagulation disorders/anticoagulant therapy
• first degree relatives with Crohn's disease or type I diabetes mellitus.
• intake of antihistamines, ketotifen, cromoglycate, acetylsalicylates, NSAIDs, anticholinergics, theophylline, β2-agonists, codeine or opioid derivatives for at least 2 weeks prior to the gastroscopy
• Intake of steroid or immunosuppressive drugs in the last 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: gastroduodenoscopy; all participants undergo a gastroduodenoscopy to use the biopsies in an Ussing chamber experiment.	Procedure: Gastroduodenoscopy; Gastroduodenoscopy with duodenal biospies: A tube is placed via the mouth into the second part of the duodenum. Biopsy forceps is used to take duodenal biopsies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacterial uptake in the duodenal biopsy measured by fluorescent intensity at the basolateral side of the ussing chamber setup.	duodenal uptake of fluorescein conjugated microorganisms	120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
duodenal permeability assessed by measuring transepithelial electrical resistance in the Ussing chamber setup	transepithelial electrical resistance	120 minutes

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Jan Tack, Professor, KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2017
• Primary Completion (Actual): April 27, 2018
• Study Completion (Actual): August 27, 2018

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: September 22, 2017
• First Posted (Actual): September 28, 2017

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: bile acid; bacterial uptake
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Dyspepsia
• Other Study ID Numbers: s56880

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No