Homo sapiens Raw sequence reads

Pathogens represent a serious threat for human health. As a consequence, in order to maintain the homeostasis and survive to pathogen attack, multicellular organisms have developed specific defense mechanisms. The immune system, particularly the innate immune one, is the most important and ancient system showing important roles in controlling microbial infections, by orchestrating the inflammatory response. When microbial infection occurs, host cells sense microbial structures (Pathogen Associated Molecular Patterns, PAMPs) through Pattern Recognition Receptors (PRRs), such as Formyl Peptide Receptors (FPRs), and initiate the immune response, which may result in alteration of cell metabolism and epigenetic regulation (histone modifications). Helicobacter pylori (H. pylori) is a major human pathogen causing chronic infection and leading toa persistent inflammatory state, risk factor for the development of both gastric and extra-gastric diseases, such as metabolic disorders and neurodegenerative diseases. Consequently, it represents a serious risk for human health, made worst since it is not a pathogen easy to eradicate. In this context, anti-inflammatory agents are a valid approach to control the H. pylori-induced outcomes. Caulerpin, bis-indole alkaloid derived from algae of the genus Caulerpa cylindracea, was found to mitigate the H. pylori-induced inflammation through the inhibition of Formyl peptide receptor 2 (FPR2), thus representing a promising therapeutic adjuvant against the H. pylori infection. The aim of the present project is to provide a comprehensive analysis of the cellular modifications induced by the H. pylori-associated inflammation, using a multi-omics approach (epigenetics, transcriptomics and metabolomics). In detail, the project aims to investigate how the metabolic reprogramming, resulting from the stimulation of AGS cells with the H. pylori culture filtrate (Hpcf) or the Hp (2-20) peptide (FPR2 pro-inflammatory agonist), affects the pro-inflammatory gene expression via epigenetic modifications. This could provide a further insight into the role of Caulerpin in mitigating the H. pylori-induced inflammation and the associated clinical outcomes.