Multifunctional properties of food-derived bioactive peptides on human health: focus on anti-inflammatory activity

Inflammation is a fundamental defense mechanism against harmful stimuli and it involves a complex network of cell types, with activation of different signaling pathways and production of a great number of inflammatory mediators. In the gut, chronic inflammation is usually associated to pathological conditions, namely celiac disease and IBD, while also increasing the risk of colorectal cancer. Intestinal inflammation induced by genetic and environmental factors determines dysbiosis and impairment of the epithelial barrier function, leading to poor nutrient absorption, bacterial infections and autoimmune conditions. Today, there is increasing interest for the use of natural products and functional foods for the prevention and treatment of chronic diseases, avoiding the side effects of synthetic drugs. Great attention was given to bioactive peptides (BPs), amino acid sequences released from food proteolysis during gastrointestinal digestion or fermentation, that have a positive impact on our health. Among the various biological activities exerted by BPs, their anti-oxidant and anti-inflammatory potential may contribute to prevent or ameliorate chronic conditions involving inflammation. In this thesis, peptides from milk and spelt flour were produced by simulated gastrointestinal digestion or microbial fermentation, fractionated by RP-HPLC and tested in vitro on different cell lines. Murine macrophages were used to evaluate BPs effects on oxidative stress and inflammation markers after LPS treatment, while Caco-2 cell line was chosen to assess their impact on intestinal barrier integrity and functionality. Colon carcinoma cells RKO were also used to study BPs ability to reduce cell proliferation. Moreover, mouse intestinal organoids were treated with BPs to study their effects on intestinal immune activation and cell differentiation. Then, we unveiled BPs amino acid sequences by Mass Spectrometry. Even though there is still much to understand about BPs absorption and kinetics in the body, our results may contribute to deepen the knowledge about their mechanisms of action and their impact on intestinal inflammation and gut health