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

Study Overview
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Brief Summary
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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.

Detailed Description
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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. This is a single centre study involving the Department of Gastroenterology and Hepatology and the Department of General Surgery at Changi General Hospital, SingHealth, Singapore. 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.

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

Conditions
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Gallstone Disease, Bile Duct Diseases

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiome, metabolome