PhD defense of Émilie BOUCHER in team TIMC TrEE on friday, the 27th of october 2023, at 2pm:

" Study of the impact of an inulin-enriched diet on gut microbiota an host immune anti-cancer response. "

Jury:

• Delphine Aldebert, Associate Professor, Hdr, Université Grenoble Alpes, Supervisor
• Nathalie Chaput, University Professor - Hospital Practitioner, Université Paris-Saclay, Reporter
• Emmanuel Scotet, Research Director, INSERM délégation Grand Ouest, Reporter
• Bruno Quesnel, University Professor - Hospital Practitioner, Université de Lille, Examiner
• Julie Charles, University Professor - Hospital Practitioner, Université Grenoble Alpes, Examiner
• Dalil Hannani, Researcher, CNRS, Invited

  Key words

Cancer, Imunity, Microbiota

  Abstract

The gut microbiota (GM) encompasses all microorganisms living in the gut lumen and is implicated in various aspects of its host’s health. The emerging health benefits of the GM make it a therapeutic target for many pathologies. In oncology, it has been shown that the microbiota plays an important role not only in preventing the disease but also in patients' response to immunotherapies. Modulating the microbiota could be a way to boost the immune system, aiding in the prevention and treatment of cancer. The composition and function of the GM, along with subsequent immunity, strongly depend on the diet. Prebiotics, also known as dietary fibers, significantly impact and diversify the GM. Modulating the GM through dietary interventions could potentially strengthen the host's immune system and enhance the anti-tumoral response. This project aimed to analyze the immunostimulatory properties of an inulin-enriched diet, a dietary fiber commonly found in vegetables. Under physiological conditions, we have demonstrated that inulin consumption modulates the composition and metabolic function of the gut microbiota. Moreover, inulin strengthens gut immunity by increasing the proportion of IFNγ-producing γδ T cells. It also promotes gut barrier integrity by upregulating genes involved in inflammation regulation. In several transplantable tumor models, the inulin-enriched diet inhibits tumor growth by promoting the infiltration of IFNγ-producing γδ, CD4+, and CD8+ T cells into the tumors. This antitumor effect is mediated by the GM and also by γδ T cells, which serve cytotoxic and helper roles. This work presents a preclinical proof of concept, highlighting the role of diet as a key regulator of anticancer immunosurveillance. These findings support and rationalize the utilization of such prebiotic approaches for the prevention and/or treatment of cancers.