Explore the Effects and Mechanisms of ERCP and EST on Biliary Microecology

The objective of this observational study is to explore the structure of biliary flora in normal people, explore the dynamic impact of ERCP and EST on biliary microecology, study the marker flora, metabolites and functional genes related to biliary diseases, explore the occurrence and development mechanism, regulatory pathways and key targets of biliary diseases, and provide new strategies for the prevention and treatment of biliary diseases from the perspective of biliary microecology.

Study Overview

• Status: Active, not recruiting
• Conditions: Gallstones; Choledocholithiasis; Cholangiopancreatography, Endoscopic Retrograde
• Intervention / Treatment: Other: Whether ERCP or EST is carried out

Detailed Description

Our research group applied the technology of macro genome sequencing to explore the biliary microecology through genomics and metabonomics analysis, describe the biliary microecology map of normal people, and build the biliary microecology framework of normal people; To explore the dynamic impact of ERCP and EST treatment on biliary tract microecology, and to further study the dynamic changes, abundance information and diversity characteristics of biliary tract microecology in patients with duodenal papillary incision and Oddi sphincter dysfunction, so as to find the marker flora and metabolites related to bile duct diseases, as well as the prognostic predictive value of specific flora and clinical diagnosis and treatment plan. This study provides a new direction for exploring the composition of human biliary microecology and the occurrence and development mechanism of biliary diseases and provides a new strategy for the treatment of patients with biliary diseases. It has important scientific significance and clinical value.

This project systematically studies the physiological characteristics of biliary tract microecology in normal people, explores the impact of ERCP and EST duodenal papillary incision on biliary tract microecology, clarifies the integrated genomic and metabolomic maps of biliary tract microorganisms in different states, compares the differences of biliary tract microecology at different key nodes, looks for the marker flora related to ERCP and EST treatment, and analyzes the correlation between the marker flora and clinical characteristics, To explore the role and mechanism of key bacteria in the occurrence and development of biliary diseases, so as to provide theoretical basis and strategies for improving prognosis for clinical treatment.

Purpose of this study

1. To construct the framework of biliary microecology in normal people, and define the structure and metabolite characteristics of biliary flora;
2. To study the short-term and long-term changes of biliary microecology in patients with ERCP, EST duodenal papillary incision and Oddi sphincter dysfunction, and explore the influence of specific pathogenic bacteria on the occurrence and development of biliary diseases
3. To screen the key flora of biliary microecology disorder before and after ERCP and EST treatment, and to explore the role and mechanism of marker flora in the occurrence and development of biliary diseases.

• Study Type: Observational
• Enrollment (Anticipated): 75

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Shulan (Hangzhou) Hospital
    • Quzhou, Zhejiang, China
      • Quzhou people's Hospital
    • Quzhou, Zhejiang, China
      • Shulan (Quzhou) Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

1. Patients with Gallbladder polyp or gallbladder adenomyosis
2. Patients with choledocholithiasis
3. Patients with previous ERCP and/or EST operations and duodenal papilla incision during operation

Description

1.Patients with Gallbladder polyp or gallbladder adenomyosis:

Inclusion Criteria:

1. The patient received laparoscopic cholecystectomy in our hospital from September 1, 2022 to September 1, 2023;
2. Age>18 years old;
3. Postoperative pathology was gallbladder polyp or gallbladder adenomyosis.

Exclusion Criteria:

1. Preoperative biliary surgery history or intraoperative biliary injuried;
2. Other complications were found.

2.Patients with choledocholithiasis:

Inclusion Criteria:

1. The patients were treated in our center from September 1, 2022 to September 1, 2023;
2. Age>18 years old;
3. Patients with choledocholithiasis received ERCP and EST treatment for the first time, but did not receive treatment in other hospitals;
4. The nasobiliary duct is to be retained to drain bile.

Exclusion Criteria:

1. Acute cholangitis;
2. There are serious complications.

3.Patients with previous ERCP and/or EST operations and duodenal papilla incision during operation:

Inclusion Criteria:

1. The patients received ERCP treatment in our center from September 1, 2022 to September 1, 2023;
2. Age>18 years old;
3. He has had ERCP and EST operations in the past, and the duodenal papilla was cut during the operation;

Exclusion Criteria:

1. Acute cholangitis;
2. Serious complications

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Gallbladder polyp or gallbladder adenomyosis; Patients with Gallbladder polyp or gallbladder adenomyosis In view of the difficulty in obtaining bile from normal people, our research team plans to select bile samples from patients undergoing laparoscopic cholecystectomy and patients with pathological diagnosis of gallbladder polyps or gallbladder adenomyosis as physiological bile of normal people.
Patients with choledocholithiasis; Patients with choledocholithiasis The research group plans to select bile samples from patients with first episode choledocholithiasis, patients receiving ERCP treatment for the first time, and patients undergoing duodenal papillary incision during EST operation to study the biliary flora of patients with choledocholithiasis. Compared with the normal group, analyze whether there are differences, similarities and uniqueness between the groups, dynamically track changes in the structure of biliary flora before and after treatment, and whether there is specific flora related to the type of disease, and compared with the existing biliary microbiome database, to study whether there are new bacterial species.	Other: Whether ERCP or EST is carried out; This project systematically studies the physiological characteristics of biliary microecology in normal people, and explores the impact of ERCP and EST duodenal papillary incision on biliary microecology.
Patients with previous ERCP and/or EST operations and duodenal papilla incision during operation; Patients with previous ERCP and/or EST operations and duodenal papilla incision during operation Bile from patients who had undergone ERCP and EST duodenal papillary incision was collected, and the long-term impact of duodenal papillary incision on biliary microecology was discussed by comparing with that of normal patients.	Other: Whether ERCP or EST is carried out; This project systematically studies the physiological characteristics of biliary microecology in normal people, and explores the impact of ERCP and EST duodenal papillary incision on biliary microecology.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successfully collect all bile samples required	Collect the required bile samples under the required conditions according to the difference of the three groups.Then DNA extraction, Illumina MiSeq sequencing and bioinformatics analysis will be performed on the collected samples.	1 week

Collaborators and Investigators

• Sponsor: Qi-Yong Li
• Investigators: Study Director: Qi-Yong Li, doctor, Shulan (Hangzhou) Hospital

Publications and helpful links

General Publications

• Yu LX, Schwabe RF. The gut microbiome and liver cancer: mechanisms and clinical translation. Nat Rev Gastroenterol Hepatol. 2017 Sep;14(9):527-539. doi: 10.1038/nrgastro.2017.72. Epub 2017 Jul 5.
• Konturek PC, Haziri D, Brzozowski T, Hess T, Heyman S, Kwiecien S, Konturek SJ, Koziel J. Emerging role of fecal microbiota therapy in the treatment of gastrointestinal and extra-gastrointestinal diseases. J Physiol Pharmacol. 2015 Aug;66(4):483-91.
• Mima K, Nakagawa S, Sawayama H, Ishimoto T, Imai K, Iwatsuki M, Hashimoto D, Baba Y, Yamashita YI, Yoshida N, Chikamoto A, Baba H. The microbiome and hepatobiliary-pancreatic cancers. Cancer Lett. 2017 Aug 28;402:9-15. doi: 10.1016/j.canlet.2017.05.001. Epub 2017 May 17.
• Molinero N, Ruiz L, Milani C, Gutierrez-Diaz I, Sanchez B, Mangifesta M, Segura J, Cambero I, Campelo AB, Garcia-Bernardo CM, Cabrera A, Rodriguez JI, Gonzalez S, Rodriguez JM, Ventura M, Delgado S, Margolles A. The human gallbladder microbiome is related to the physiological state and the biliary metabolic profile. Microbiome. 2019 Jul 4;7(1):100. doi: 10.1186/s40168-019-0712-8.
• Shen H, Ye F, Xie L, Yang J, Li Z, Xu P, Meng F, Li L, Chen Y, Bo X, Ni M, Zhang X. Metagenomic sequencing of bile from gallstone patients to identify different microbial community patterns and novel biliary bacteria. Sci Rep. 2015 Dec 2;5:17450. doi: 10.1038/srep17450.
• Ye F, Shen H, Li Z, Meng F, Li L, Yang J, Chen Y, Bo X, Zhang X, Ni M. Influence of the Biliary System on Biliary Bacteria Revealed by Bacterial Communities of the Human Biliary and Upper Digestive Tracts. PLoS One. 2016 Mar 1;11(3):e0150519. doi: 10.1371/journal.pone.0150519. eCollection 2016.
• Swidsinski A, Ludwig W, Pahlig H, Priem F. Molecular genetic evidence of bacterial colonization of cholesterol gallstones. Gastroenterology. 1995 Mar;108(3):860-4. doi: 10.1016/0016-5085(95)90461-1.
• Kawai M, Iwahashi M, Uchiyama K, Ochiai M, Tanimura H, Yamaue H. Gram-positive cocci are associated with the formation of completely pure cholesterol stones. Am J Gastroenterol. 2002 Jan;97(1):83-8. doi: 10.1111/j.1572-0241.2002.05425.x.
• Kose SH, Grice K, Orsi WD, Ballal M, Coolen MJL. Metagenomics of pigmented and cholesterol gallstones: the putative role of bacteria. Sci Rep. 2018 Jul 25;8(1):11218. doi: 10.1038/s41598-018-29571-8. Erratum In: Sci Rep. 2020 Mar 4;10(1):4347.
• Law R, Baron TH. ERCP. Gastrointest Endosc. 2013 Sep;78(3):428-33. doi: 10.1016/j.gie.2013.06.018. No abstract available.
• Li QY, Pan L, Ling Q, He JD, Zhang LX, Zheng SS. Single-operator wire-guided cannulation technique enables easier cannulation of endoscopic retrograde cholangiopancreatography. Dig Dis Sci. 2012 Dec;57(12):3293-8. doi: 10.1007/s10620-012-2274-5. Epub 2012 Jun 27.
• Li QY, Chen KJ, Jin J, Zheng SS. Guide wire-assisted technique to access the bile duct with biopsy forceps for repositioning and removal of metal stents. Endoscopy. 2013;45 Suppl 2 UCTN:E273-4. doi: 10.1055/s-0033-1344591. Epub 2013 Sep 5. No abstract available.
• Williams EJ, Green J, Beckingham I, Parks R, Martin D, Lombard M; British Society of Gastroenterology. Guidelines on the management of common bile duct stones (CBDS). Gut. 2008 Jul;57(7):1004-21. doi: 10.1136/gut.2007.121657. Epub 2008 Mar 5.
• Saito H, Kadono Y, Shono T, Kamikawa K, Urata A, Nasu J, Imamura H, Matsushita I, Tada S. Remaining issues of recommended management in current guidelines for asymptomatic common bile duct stones. World J Gastroenterol. 2021 May 14;27(18):2131-2140. doi: 10.3748/wjg.v27.i18.2131.
• Kageoka M, Watanabe F, Maruyama Y, Nagata K, Ohata A, Noda Y, Miwa I, Ikeya K. Long-term prognosis of patients after endoscopic sphincterotomy for choledocholithiasis. Dig Endosc. 2009 Jul;21(3):170-5. doi: 10.1111/j.1443-1661.2009.00880.x.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: October 20, 2022
• First Posted (Actual): October 25, 2022

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathological Conditions, Anatomical; Gallbladder Diseases; Biliary Tract Diseases; Bile Duct Diseases; Common Bile Duct Diseases; Calculi; Cholelithiasis; Cholecystolithiasis; Gallstones; Choledocholithiasis
• Other Study ID Numbers: shulan(hangzhou)1

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