Bile Acids and Microbiome in Early Colorectal Carcinogenesis
NCT Number: NCT06502704
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Colorectal Neoplasms|Colorectal Cancer|Colorectal Polyp|Microbiome|Bile Acid Malabsorption
Sponsor: Vilnius University
Collaborators: Vilnius University Hospital Santaros Klinikos
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-07-05
Completion Date: 2025-01-01
Locations: Vilnius University Hospital Santaros Klinikos, Vilnius, 08661, Lithuania

Summary:
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.

Primary Outcome Measures: Microbiome and bile acid composition correlation to dysplastic changes, Microbiome and bile acid composition changes will be detected and correlated with progression of the dysplastic changes within the epithelium of the large bowel., Through study completion, an average of 2 years
Secondary Outcome Measures: Bile acid composition in healthy participants, Compare bile acid composition of healthy controls to patients with early and advanced adenomas and colorectal cancer, novel bile acid identification that could play a role in the adenoma-carcinoma sequence and identify the diagnostic potential of bile acid composition patterns, Through study completion, an average of 2 years|Bile acid composition in urine, stool and serum, Determine the bile acid composition in urine, stool and serum of healthy controls, Through study completion, an average of 2 years