Studying the effects of anti-inflammatory dietary compounds using novel in vitro 3D co-culture models of colon chronic inflammation

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"Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are non- communicable diseases (NCDs) characterised by chronic inflammation. The current standard of care of IBD and CRC includes anti-inflammatory drugs, which act on the symptoms while poorly addressing the causative factors [1]. Therefore, treatments result merely palliative, addressing the need to find the most appropriate preventive and/or therapeutic protocol.Since the inflammation manifested with IBD and CRC tends to be persistent, unresolved and age-related, recent studies have investigated how lifestyle habits could influence and prevent inflammation's onset, progression and comorbidities [3]. In this regard, it has been recognized the primary role of the meta-exposome, a combination of environmental factors, such as diet, physical activity, exposure to xenobiotics, and microbiome, among others [2, 4]. Dietary choices play a pivotal role in regulating homeostasis and physical wellbeing since food-derived bioactive compounds can actively balance effector (pro-inflammatory) and regulatory (anti-inflammatory) functions [5-7]. This modulation is determined by nutrients' ability to shape genome and epigenome, rearranging their expression profiles. These observations warrant further investigation into food-derived bioactive compounds and their ability to regulate inflammation.We hypothesize that approaching different dietary regimens (Western diet VS Mediterranean diet) leads to a specific modulation of the inflammatory response, both directly, through the immune and adipose systems, and indirectly, through the signals mediated by the microbiome. Since the inflamed phenotype is typical of IBD and CRC, the current project aims to:1. Developa3Dco-culturemodelthatmimicstheintestinalepithelium;2. Dissect the crosstalk between inflammatory cytokines and nutritionalregimens;3. Assess and compare transcriptome and epigenome profiles followingtreatment."