The role of gut microbiota, immune system, and autophagy in the pathogenesis of inflammatory bowel disease: Molecular mechanisms and therapeutic approaches

Abstract

The role of gut microbiota, immune system, and autophagy in the pathogenesis of inflammatory bowel disease: Molecular mechanisms and therapeutic approaches Beatrice Garavaglia a,1, Letizia Vallino a,1, Angela Amoruso b, Marco Pane b, Alessandra Ferraresi a, Ciro Isidoro a,* a Laboratory of Molecular Pathology, Department of Health Sciences, Universit`a del Piemonte Orientale, Via P. Solaroli 17, 28100, Novara, Italy b Probiotical Spa, via E. Mattei, 3, 28100, Novara, Italy A R T I C L E I N F O Handling Editor: Prof A Angelo Azzi Keywords: Crohn’s disease Ulcerative colitis immune system Autophagy Microbiota Probiotics A B S T R A C T The crosstalk between gut microbiota, intestinal epithelial cells, and innate and adaptive immune system governs the maintenance of the intestinal homeostasis. Any interference in this tight dialogue and in the processes preserving cellular homeostasis (e.g., autophagy) may dysregulate the immune response and impair the clearance of harmful bacteria favoring the dysbiotic alteration of the microbial flora that leads to chronic inflammation. Gut dysbiosis is strongly associated with gastrointestinal inflammatory disorders, among them the inflammatory bowel disease (IBD). This review discusses the current knowledge on IBD, from the genetic background of high-risk patients to the molecular mechanisms underlying the disease, the contribution of the microbial flora, and the role of autophagy in intestinal epithelia homeostasis. Further, we illustrate the state of art regarding the targeted-nutritional approaches aimed to restore the beneficial crosstalk between an “antiinflammatory” microbiota and the host. Analysis of the molecular pathogenesis of IBD will help identify genetic and diet-associated risk factors and thus suggest personalized strategies to prevent and manage the disease to improve quality of life with long-term maintenance of the remission phase.