Gut Microbiome and Metabolome in Patients With Gallstone Disease After Surgical and Endoscopic Interventions

A Prospective Cohort Study of Translational Changes in Gut Microbiome and Metabolome in Patients With Gallstone Disease After Surgical and Endoscopic Interventions

The goal of this longitudinal observational cohort study is to examine the changes in the composition and diversity of gut microbiome and systemic metabolome in patients with symptomatic gallbladder stones with or without concomitant common bile duct (CBD) stones who will be undergoing cholecystectomy with or without prior endoscopic sphincterotomy (ERCP-ES) and CBD stones extraction. The main questions it aims to answer are whether there are:

• differences in gut microbiome diversity and composition before and after cholecystectomy
• differences in systemic metabolome before and after cholecystectomy
• gut microbiome and systemic metabolome changes after cholecystectomy

Participants will be asked to provide stool, urine, plasma and saliva samples prior to and 1-6 months after cholecystectomy. For patients with concomitant CBD stones who undergo ERCP-ES before cholecystectomy, bile specimens will be collected from the bile duct during ERCP-ES as well as the gallbladder and/or during cholecystectomy.

Study Overview

• Status: Recruiting
• Conditions: Bile Duct Diseases; Gallstone Disease

Detailed Description

This is a longitudinal observational cohort study that will examine the changes in the composition and diversity of gut microbiome and systemic metabolome in patients with symptomatic gallbladder stones with or without concomitant CBD stones who will be undergoing cholecystectomy with or without prior ERCP-ES and CBD stones extraction.

Patients with symptomatic gallstones with or without CBD stones being planned for cholecystectomy will be recruited from both inpatient and outpatient settings. Upon enrolment, baseline clinical characteristics will be recorded, and biospecimens (stool, urine, plasma and saliva) will be collected prior to cholecystectomy for subsequent gut microbiome and systemic metabolome analysis. For patients with concomitant CBD stones who undergo ERCP-ES before cholecystectomy, bile specimens will be collected from the bile duct during ERCP-ES as well as the gallbladder during cholecystectomy, for subsequent bile microbiome analysis. After cholecystectomy, during the scheduled clinic review at 1 to 6 months post-surgery, patients will be reviewed for symptoms of post cholecystectomy syndrome (PCS) or post cholecystectomy diarrhoea (PCD), and biospecimens (stool, urine, plasma and saliva) will again be collected for subsequent gut microbiome and systemic metabolome analysis. The microbiome profile of the study cohort will be compared at baseline with matched controls from other defined cohorts. Post cholecystectomy, the study cohort will also be compared with matched cohort with cholecystectomy duration of more than 12 months.

• Study Type: Observational
• Enrollment (Estimated): 65

Contacts and Locations

• Study Contact: Name: Seok Hwee Koo; Phone Number: +6568504929; Email: seok_hwee_koo@cgh.com.sg
• Study Contact Backup: Name: Nway Nway Aye; Phone Number: +6569365737; Email: nway_nway_aye@cgh.com.sg

Study Locations

• Singapore
  • Singapore
    • Singapore, Singapore, Singapore, 529889
      • Recruiting
      • Changi General Hospital
      • Sub-Investigator: Seok Hwee Koo
      • Sub-Investigator: Andrew Boon Eu Kwek
      • Sub-Investigator: Chin Kimg Tan
      • Sub-Investigator: Andrew Siang Yih Wong
      • Sub-Investigator: Adrian Kah Heng Chow
      • Sub-Investigator: Nita Thiruchelvam
      • Sub-Investigator: Jinlin Lin
      • Sub-Investigator: Annalisa Ya-Lyn Ng
      • Sub-Investigator: James Weiquan Li
      • Sub-Investigator: Daphne Shih Wen Ang
      • Sub-Investigator: Yu Jun Wong
      • Sub-Investigator: Kenneth Weicong Lin
      • Sub-Investigator: Nicholas Tee
      • Sub-Investigator: Amanda Huimin See
      • Contact: Siok Luan Ong; Phone Number: +65-64267280; Email: ong.siok.luan@singhealth.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This single centre study at Changi General Hospital will enrol up to 65 patients aged 21 to 80 years with symptomatic gallstone disease and/ or bile duct stones who will be undergoing cholecystectomy with or without concomitant ERCP-ES as part of standard clinical treatment. There will not be stratification by demographics.

Description

Inclusion Criteria:

• Aged 21 years to 80 years
• Diagnosis of symptomatic gallstone disease without or with concomitant bile duct stones based on prior diagnostic radiological imaging such as transabdominal ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) or endoscopic ultrasound (EUS).
• Will be scheduled for cholecystectomy with or without concomitant ERCP-ES for treatment.
• Patient is willing to provide informed consent before enrolment in the study.

Exclusion Criteria:

• Subjects undergoing ERCP-ES with no intention for future cholecystectomy
• Use of antibiotics or probiotics within 1 month (exception: use of antibiotics within 48 hours of cholecystectomy or ERCP, as metagenomics will be able to sequence both dead and live bacteria, and marked compositional change is not expected within this time frame)
• Presence of malignancy diagnosed within the last 1 year
• Previous gastrectomy, appendicectomy, small bowel or large bowel surgery
• Inflammatory bowel disease
• Active gastrointestinal tract infections

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiome profile using metagenomic shotgun sequencing	Fresh stool samples will be collected for microbial DNA extraction prior to and 1-6 months after cholecystectomy. Microbial DNA will be extracted from the stool samples and used for metagenomic shotgun sequencing.	1-6 months
Systemic metabolome profile using targeted and untargeted metabolomic analysis	Urine, plasma and saliva samples will be collected for metabolomic profiling prior to and 1-6 months after cholecystectomy.	1-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bile microbiome profile using metagenomic shotgun sequencing	Bile samples will be collected for microbial DNA extraction ERCP and endoscopic sphincterotomy	1-6 months

Collaborators and Investigators

• Sponsor: Changi General Hospital
• Investigators: Principal Investigator: Tiing Leong Ang, Changi General Hospital

Publications and helpful links

General Publications

• Latenstein CSS, Alferink LJM, Darwish Murad S, Drenth JPH, van Laarhoven CJHM, de Reuver PR. The Association Between Cholecystectomy, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease: A Population-Based Study. Clin Transl Gastroenterol. 2020 Apr;11(4):e00170. doi: 10.14309/ctg.0000000000000170.
• Chen Y, Wu S, Tian Y. Cholecystectomy as a risk factor of metabolic syndrome: from epidemiologic clues to biochemical mechanisms. Lab Invest. 2018 Jan;98(1):7-14. doi: 10.1038/labinvest.2017.95. Epub 2017 Sep 11.
• Di Ciaula A, Garruti G, Wang DQ, Portincasa P. Cholecystectomy and risk of metabolic syndrome. Eur J Intern Med. 2018 Jul;53:3-11. doi: 10.1016/j.ejim.2018.04.019. Epub 2018 Apr 26.
• Reid FD, Mercer PM, harrison M, Bates T. Cholecystectomy as a risk factor for colorectal cancer: a meta-analysis. Scand J Gastroenterol. 1996 Feb;31(2):160-9. doi: 10.3109/00365529609031981.

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: January 17, 2023
• First Posted (Actual): January 19, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: microbiome; metabolome
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Cholelithiasis; Bile Duct Diseases
• Other Study ID Numbers: GMM1

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