HDR defense :

Adaptation of nutrition‑intestine‑host interactions to contemporary diets: the role of dietary fructose as a major nutritional determinant

During the past decades, the rise in fructose consumption in contemporary diets has dramatically altered the intake of simple sugars and raised new questions about their physiological effects. My work presented in this manuscript has helped to partly answer those questions. Initially carried out mainly on pre‑clinical models, it allowed us to characterize the regulatory mechanisms of intestinal fructose absorption and the systemic consequences of its metabolism, particularly in extra‑hepatic tissues. Over time, my research also showed that fructose’s effects are not limited to its absorption and host metabolism, but also involve the repercussions of its malabsorption on the intestinal ecosystem.

Integrating the gut microbiota into my studies revealed its central role in mediating fructose effects, and more broadly the effects of obesogenic diets. These findings demonstrated that the host response depends not only on chronic exposure but also on rapid microbial adaptation mechanisms occurring within a single meal or during the first days of exposure. Building on these investigations of interactions among dietary sugars, the gut, and the host, my current work aims to establish causal links between fructose malabsorption, gut‑microbiota reconfiguration, and physiological or behavioral outcomes, especially via the gut‑brain axis. It focuses on the role of the microbiota and entero‑endocrine plasticity in visceral hypersensitivity and mood disorders, as well as on the ecological dynamics of bacterial communities in response to fructose. This theme is now moving toward more translational approaches, including the creation of human cohorts and the integration of clinical, metagenomic, and metabolomic data, to identify functional signatures in humans that could open the way to new preventive or therapeutic strategies.

Jury members:

• David Ribet, Directeur de Recherche INSERM, ROUEN.
• Guillaume Walther, Professeur des Universités, Avignon
• Sophie Blat, Chargée de Recherche, Rennes.
• Mouna Hanachi, PUPH, Hôpital Paul Brousse, Paris.
• Filipe De Vadder, Chargé de recherche CNRS, Lyon.
• Sandra Guilmeau, Maitre de conférences universitaire, Institut Cochin, Paris