Colorectal cancer (CRC) remains a major global health burden, and early detection through population-based screening programs significantly reduces both incidence and mortality. Although gut microbiome-based biomarkers have emerged as promising non-invasive tools for CRC detection, limited evidence is available regarding patient acceptance and compliance with microbiome-based screening studies, factors that may influence their future implementation in clinical practice. We conducted a preliminary analysis of an ongoing multicenter, prospective observational study designed to develop a gut microbiome-based diagnostic tool for CRC and advanced colorectal adenomas in fecal immunochemical test (FIT)-positive individuals. The primary objective of this preliminary analysis was to evaluate patient acceptance and compliance with participation in a microbiome-based study within an organized CRC screening setting. Secondary objectives included describing the clinical, endoscopic, and histopathological characteristics of the enrolled cohort. FIT-positive individuals referred for screening colonoscopy at participating Italian centers were screened for eligibility, underwent colonoscopy, and were invited to provide a stool sample for microbiome analysis. A total of 315 individuals were screened, of whom 212 (67%) were enrolled. Among eligible patients, 90% agreed to enroll after receiving study information. Overall, 200 (94%) of enrolled individuals completed the required study activities, including stool sample collection and colonoscopy, indicating high compliance with study procedures. Colonoscopy was performed in 209 patients (99% of enrolled patients). CRC was detected in 7 patients (3%), and advanced colorectal adenomas in 39 (18%), while 86 (41%) colonoscopies were negative. The positive predictive value of FIT was 3.35% for CRC and 18.66% for advanced adenomas. In our preliminary analysis, patient acceptance and compliance with microbiome-based sampling were high among FIT-positive individuals undergoing CRC screening. These findings support the feasibility of conducting microbiome-based studies within organized screening programs. Analyses aimed at developing and validating the microbiome-based diagnostic tool are currently ongoing and are beyond the scope of the present report.

Proteobacteria are a phylum of Gram-negative bacteria that, although normally a minor component of the healthy gut microbiota, can be markedly increased in many conditions. Their overgrowth is in fact linked to inflammation, impaired epithelial barrier function, and diseases such as inflammatory bowel disease, metabolic syndrome, and gastrointestinal cancers. Key species, like Escherichia coli and Helicobacter pylori, can promote disease through specific etiopathogenetic mechanisms, from genotoxin production to immune activation: this peculiarity can be used for diagnostic purposes, and in some cases even as therapeutics. Emerging microbiota-targeted therapies—such as dietary modulation, probiotics, fecal microbiota transplantation, bacteriophages, and engineered bacteria—aim to restore microbial balance. This narrative review deals with the dual role of Proteobacteria as both pathogens and diagnostic–therapeutic tools, which is crucial for advancing personalized microbiome-based medicine.