Faecal Microbiota Characterization in Lynch Syndrome (LS) Patients With or Without Colorectal Neoplasia

Colorectal cancer (CRC) is the second cause of cancer-related death in western countries. CRC prevention and screening are major public health issues. Better knowledge of colorectal carcinogenesis could lead to better prevention. Gut microbiota (GM) is a complex community of bacteria, fungi, protozoa, viruses and bacteriophages which live in a symbiotic and epigenetic relationship with the host. GM can promote either digestive health or CRC through inflammatory and proliferative effects. Lynch syndrome (LS) is the most common familial CRC syndrome with a lifetime CRC risk of 52% in women and 69% in men. The risk of CRC depends upon type of altered mismatch-repair gene and environmental factors (diet, exercise, obesity, tobacco and alcohol intake, etc.). Regular surveillance including annual or biannual colonoscopy is recommended in LS patients. Chemoprevention has the potential to represent a cost-effective intervention in these high-risk patients and could allow a delay in colonoscopy surveillance. Regular low dose aspirin use is associated with a 20 to 30% reduction in the risk of sporadic colonic adenomas and CRC. The real benefit of aspirin is still to be consolidated. AAS-Lynch trial is an ongoing prospective multicenter (n=37), double-blind, placebo-controlled, randomized clinical trial, designed to investigate whether daily aspirin, at a dose of 100 or 300 mg compared with placebo, would decrease the occurrence or recurrence of colorectal adenomas in LS patients. The primary endpoint is the number of patients with at least one adenoma detected by chromo-endoscopy 48 months after initial colon clearance. At randomization and at the end of study, stool collection, blood collection, quality of life questionnaire, validated food frequency questionnaire (SU-VI-MAX2) and physical activity questionnaire are performed. The ongoing AAS-Lynch study allow accessing to a unique fecal collection in very well characterized LS patients including a comprehensive dietary evaluation at high risk for colorectal neoplasia and planned colonoscopy surveillance during a 48 months follow-up, exposed or not exposed to chronic low dose aspirin. The expertise of the scientific consortium with state of the art microbiota analysis, the comprehensive collection of data and the prospective design of the study will allow the evaluation of the true role of gut microbiota in CRC carcinogenesis.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* Patients included in the AAS-Lynch study (NCT02813824 on clinicaltrials.gov)
* Fecal samples taken for the AAS-Lynch study (NCT02813824 on clinicaltrials.gov)
* Food questionnaires collected as part of the AAS-Lynch study (NCT02813824 on clinicaltrials.gov)

Exclusion Criteria:

* Patients who did not included in the AAS-Lynch study (NCT02813824 on clinicaltrials.gov)
* Patients who did not consent for the Fecal samples in AAS-Lynch study (NCT02813824 on clinicaltrials.gov)
* Patients who did not do the Food questionnairy in AAS-Lynch study (NCT02813824 on clinicaltrials.gov)

• DERIVEDDemare N, Bridier-Nahmias A, Carbonnelle E, Magnan M, Bellicha A, Marin J, Arnault N, Benallaoua M, Ait Omar A; AAS-Lynch study group 2024; Benamouzig R, Deschasaux-Tanguy M. Association between dietary intakes and gut microbiota composition in individuals with Lynch syndrome: a cross-sectional analysis of the AAS-Lynch study. Am J Clin Nutr. 2026 May 28;124(3):101382. doi: 10.1016/j.ajcnut.2026.101382. Online ahead of print. PMID 42214493