Study of metabolic alterations in inflammatory bowel diseases

Inflammation is a defence mechanism, which constitutes a protective response, following harmful action of physical, chemical and biological agents, whose ultimate goal is the elimination of the initial cause of cellular or tissue damage, as well as the start of the reparative process. Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract of uncertain origin, which includes ulcerative colitis (UC) and Crohn’s disease (CD). Tissue and systemic metabolism are particularly affected by the presence of an inflammation process and a consequently immune response. Here, the metabolic changes happening in IBD were studied analysing different type of biological samples coming from IBD affected patients and healthy individuals. Plasma, ileum and colon biopsies were analysed by GC-MS and faeces samples by GC-MS and 1H-NMR. Furthermore, to have a more complete understanding of IBD pathogenesis and persistence, microbiota was characterised in faeces samples. The metabolites content in biopsies, plasma and faeces and the faeces microbiological profiles were significantly different between IBD and healthy subjects. Energetic metabolism was found particularly involved in the disease. In faeces, changes in metabolites showed a good correlation with microbiota profile. Between all the altered metabolites, nicotinic acid was found to decrease in faeces of IBD patients respects to healthy subjects. As in literature, nicotinic acid seems to have an anti-inflammatory effect, an in vitro model of intestinal inflammation was obtained with differentiated Caco-2 cells in which inflammation was induced with LPS and IL-1β. Cells were then co-treated with LPS and IL-1β together with nicotinic acid. The in vitro results showed that nicotinic acid was able to reduce inflammation by reducing IL-8 production. In addition, nicotinic acid had an effect in restoring the levels of several metabolites, which changes were caused by the inflammatory stimuli. Concluding, this study underlines the potential role of metabolomic and inter-omics approaches in understanding the alteration of metabolic pathways involved in IBD. Lastly, it also proved the beneficial effect on nicotinic acid on intestinal inflammation and how it is achieved through metabolism changes.