Improving Colorectal Cancer Early Screening in Portugal: Identification of Gut Microbiome Biomarkers in Stool (GUTBIOME-PT)

This study will analyse the gut microbiome in stool samples collected from individuals living in the Lisbon Metropolitan Area, Portugal. Using shotgun metagenomics, the investigators aim to identify microbiome biomarkers associated with the early detection of CRC and the progression of precancerous lesions (adenomas). The identified biomarkers will be tested to develop a non-invasive and highly sensitive screening tool for CRC and precancerous lesions.

Primary Objective:

To identify gut microbiome biomarkers in faecal DNA associated with CRC and/or high-risk adenomas.

Secondary Objectives:

i) Establish the correlation between FIT results, faecal microbiome testing and colonoscopy results.

ii) Estimate the incidence of CRC in the Lisbon Metropolitan Area among individuals aged 40-74 years, stratified by sex and age group.

iii) Analyse associations between clinical data (e.g., clinical history, lifestyle, and dietary habits), faecal microbiome profiles, FIT results, and colonoscopy outcomes, comparing individuals with CRC and/or high-risk adenomas against healthy individuals, for the total sample and by sex and age group; iv) Identify risk factors (e.g., clinical history, lifestyle, dietary habits) associated with CRC development, stratified by sex and age group.

Study Design:

This is an observational, prospective, longitudinal study involving individuals aged 40-74 years residing in the Lisbon Metropolitan Area who voluntarily enrol in the study.

Participants meeting all inclusion criteria and no exclusion criteria (as detailed in the relevant section) will be included. Based on sample size calculations using the Neyman allocation formula and taking as a reference the distribution of the population living in the Lisbon Metropolitan Area (stratified by sex and age groups: 40-49, 50-59, 60-64, 65-69 and 70-74 years), along with assumptions of the overall FIT test prevalence and sensitivity, a total of 30.000 participants will be enrolled.

At baseline, participants will provide a faecal sample within 2 to 10 days of enrolment. Demographic, clinical, and lifestyle data-including age, family history of CRC, personal medical history, smoking habits, physical activity levels, stress, and body mass index (BMI)-will be collected via self-administered questionnaires. Dietary habits and adherence to the Mediterranean diet will be assessed through telephone interviews.

Participants will be followed for six years, with faecal samples collected every 2 years. Clinical and lifestyle data will also be updated every two years throughout the study period.

Inclusion criteria

• Ability to provide written informed consent and comply with study procedures
• Reside in the Lisbon Metropolitan Area,, Portugal
• Age from 40 to 74 years

Exclusion criteria

• Age < 40 years or ≥ 75 years
• Unable to provide informed consent
• Refusal to provide stool samples
• Active oncological disease
• Personal history of CRC
• Personal history of colon adenomas removed in the last 24 months
• First-degree family history of CRC
• Previous diagnosis of inflammatory bowel disease (ulcerative colitis, Crohn's disease or indeterminate colitis), inflammatory bowel syndrome, persistent and infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhoea of unknown aetiology or recurrent infection by Clostridioides difficile
• Severe cardiovascular or heart diseases with medical diagnosis
• Severe renal failure requiring hemodialysis
• Severe lung disease
• Pregnancy