Modelling endocrine-Immune interactions in response to food Proteins (IMMPRO).

Objective

Obesity and overweight are major contributors to chronic diseases like type 2 diabetes, often accompanied by chronic inflammation, which can affect the gastrointestinal tract. Enteroendocrine cells are a specialized cell population found along the intestine that secrete multiple hormones in response to meal-related stimuli. Among these hormones, glucagon-like peptide-1 (GLP-1) plays a vital role in enhancing insulin secretion, suppressing appetite, and maintaining glucose balance. Additionally, GLP-1 receptor is expressed on immune cells, including intestinal intraepithelial lymphocytes, which regulate mucosal immunity by producing anti-inflammatory cytokines and help maintain barrier integrity. Indeed, it has been suggested a bidirectional relationship between hormonal secretion and immune function, where gut hormones can influence immune activation and inflammation, while inflammatory processes can, in turn, alter hormone secretion. We aim to understand the effect of peptides derived from gastrointestinal digestion of milk, soybean and pea on the modulation of GLP-1 secretion and their effect on intestinal inflammation through that hormone. To investigate this aim we will use a multi-approach strategy that involves the use of mouse intestinal organoids, immune-epithelial organoids, an isolated perfused model of the mouse intestine, and mouse studies, combined with state-of-the-art molecular characterization (immunohistochemistry, cellular analysis, peptidomic characterization by tandem mass spectrometry). Using these approaches, we aim to address the critical need to understand the molecular links between protein digestion, hormone secretion, and immune activation, and to identify food peptides that enhance GLP-1 release and modulate immune responses. This knowledge could pave the way for more sustainable dietary interventions, potentially contributing to the development of novel, food-based therapies for obesity, type 2 diabetes, and inflammatory bowel diseases