PhD

PhD student: Noémie Demaré

Title: Study of associations between dietary profiles, gut microbiota diversity and colonic neoplasia in patients with lynch syndrome included in the prospective AAS-Lynch trial

Supervisor(s): Robert Benamouzig and Mélanie Deschasaux-Tanguy

Doctoral school: Institut Galilée – ED GALILEE – ED 146

Promotion: 2023/2024

Thesis abstract:

Lynch syndrome (LS) is the most common form of hereditary predisposition to colorectal cancer (CRC), accounting for 3% of CRCs. Individuals affected by LS are at greater risk to develop adenomas and colorectal cancers with a 10 % risk to developing colorectal cancer at age 50 and 40% at age 70. Recent observational data in humans and experimental studies on rodents have suggested that the intestinal microbiota may contribute to the pathogenesis of CRC, notably, depending on the context and the genetic factors of the host, promoting tumour progression via its inflammatory and proliferative effects.

The relationship between nutritional factors and the risk of colorectal cancer is well established and could partly relate to the intestinal microbiota. Depending on dietary intakes, the intestinal microbiota is indeed likely to produce either oncometabolites or tumour suppressive metabolites. Moreover, “Western” diets have been associated to a dysbiosis of intestinal microbiota resulting in the production of pro-inflammatory metabolites, which could increase the risk of neoplasia. On the contrary, the intake of dietary fibres lead to the production short chain fatty acids (SCFAs) by intestinal bacteria. SCFAs help to maintain mucosal integrity and suppress inflammation and carcinogenesis, making them an interesting opening for the prevention of CRC.

Hence, the interplay between diet and intestinal microbiota could be involved in the development of colorectal cancer. Nevertheless, there is little information on the eating habits of individuals suffering from Lynch syndrome in relation to their intestinal microbiota and their risk of developing adenomas and CRCs. Such information could improve the understanding and prevention of colorectal cancer for these individuals suffering from Lynch syndrome.

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