Bile Acids and Microbiome in Early Colorectal Carcinogenesis

Vilnius University

Status: Enrolling

Conditions: Colorectal Polyp; Microbiome; Colorectal Neoplasms; Bile Acid Malabsorption; Colorectal Cancer

Study type: Observational

Funder types: Other

Identifiers

NCT06502704

2024/5-1587-1047

Details and patient eligibility

About

Currently colorectal cancer pathogenesis is mainly explained by the adenoma-carcinoma sequence theory that was proposed more than half a century ago. It mainly focuses on the explanation of genetic mutations that develop throughout the disease course. However, several studies argue that there are also noticeable bile acid metabolism changes and microbiome composition changes within in colorectal cancer patients. However, carcinoma is the final step in the sequence, and prior steps are noticeably less well studied. Thus, the investigators hypothesize, that changes within microbiome and the changes in the urine, serum and gut bile acid composition further leads to the development of colorectal adenoma and subsequent invasive carcinoma.

Adult participants (15 per group) referred for colonoscopy and histologically diagnosed with small (<1cm) adenomas, large (>1cm) adenomas, invasive CRC will be included in the study, as well as 15 healthy controls. Fecal samples will be collected from all participants before bowel preparation. Additionally, urine and serum samples will be collected. Participants will undergo polypectomy, endoscopic mucosal resections, depending on the location, size and histology of the polyp found. During colonoscopy the mucosal biopsy specimens from the lesion and from the healthy bowel -terminal ileum, and colon will be obtained using sterile biopsy forceps. The collected samples will be stored for bile acid and microbiome analysis and for possible further pathology and genetic testing. Healthy participants without visible colorectum pathology during colonoscopy will undergo colon and terminal ileum mucosal sampling.

The investigators plan to evaluate the correlation between the urine and gut microbiome changes and bile acid composition and concentration in adenoma-carcinoma sequence and possibly determine novel bile acids. In addition, fecal, urine and tissue samples will be explored for gut microbiota and bile acid composition changes in healthy and along the adenoma-carcinoma sequence, with the possibility to propose a diagnostic test.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Patients that have clinical indications for colonoscopy

Exclusion criteria

• Pregnancy
• Immunocompromised
• Previously diagnosed colorectal diseases
• Radiotherapy to the pelvis
• Long term antibiotic use within 6 months
• Continuous use of proton pump inhibitors

Trial design

60 participants in 4 patient groups

Control

Description:

No pathology upon colonoscopy

Small adenoma

Description:

\< 1cm size polyp upon colonoscopy

Large adenoma

Description:

\> 1cm size polyp upon colonoscopy

Cancer

Description:

Adenocarcinoma upon colonoscopy