Urinary and Faecal Amino-Acids as Biomarkers for Colorectal Neoplasia in Lynch Syndrome-A Prospective Longitudinal...

In Lynch syndrome, colonoscopy surveillance for colorectal cancer (CRC) is burdensome and post-colonoscopy CRCs still occur. Unlike the faecal immunochemical test (FIT), gut metabolomic alterations including amino-acids have shown potential as non-invasive biomarkers for detecting both advanced and non-advanced sporadic colorectal neoplasia. We aimed to evaluate the potential of faecal and urinary amino-acids to refine colonoscopy surveillance in Lynch syndrome. Individuals with Lynch syndrome collected faeces and urine 3 months before and 3-6 months after surveillance colonoscopy. Individuals with and without relevant neoplasia (defined as CRC, adenomas and advanced serrated polyps) were matched based on age, sex, smoking, and diet. Using liquid chromatography-tandem mass spectrometry and Random Forest classification, we assessed the diagnostic performance for relevant neoplasia of 20 faecal amino-acids (± positive FIT at 2.55 μg Hb/g faeces) and 20 urinary amino-acids. Among the 150 included individuals (118 collected faeces and 64 urine), 3% had CRC, 5% advanced adenomas, 3% advanced serrated polyps and 40% non-advanced adenomas at colonoscopy. In individuals with relevant neoplasia, faecal taurine and urinary citrulline, threonine and ornithine were elevated. Amino-acids showed 80% (faeces) and 88% (urine) sensitivity for relevant neoplasia, with higher specificity in urine (60%) than faeces (33%). Adding FIT-results to amino-acids outcomes did not improve diagnostic accuracy. After polypectomy, several faecal and urinary amino acids shifted towards levels of individuals without neoplasia. This exploratory study in Lynch syndrome highlights faecal and urinary amino acids as promising non-invasive biomarkers for postponing colonoscopy and follow-up after polypectomy, although these findings require external validation.