Enteric Neuro-Immune units (eNIu) as sensors of environmental factors, their role in gut homeostasis (health and disease) and their impact on brain-gut axis physiology

Immunological studies are crucial for the Public health, as they provide knowledge for the development of new treatments against inflammatory or autoimmune diseases. One of the major concerns in gastro-intestinal medicine is to understand how in the mucosal environment Neuro-Immune units can promote health or disease. Tackling these aspects requires genetic, cellular and molecular studies, which despite new technological progress in the last years, still remain to be elucidated. The Gastrointestinal (GI) tract is the centre of absorption and secretion, which is essential for growth, digestion, and protection against pathogenic microorganisms. Inflammatory Bowel Diseases (IBD), including Ulcerative colitis (UC), Crohn's disease (CD) and Colorectal cancer (CRC) are multifactorial, heterogenous and chronic idiopathic disorders that cause inflammation of the gastro-intestinal tract, in which inadequate host-microbe relationship leads to a breakdown of intestinal homeostasis. The 'rise' of IBD and CRC in developed countries can be attributed to an increasingly ageing population, unfavourable modern dietary habits, inadequate physical exercise, environmental factors (sporadic development) or genetic factors. IBD and CRC are considered to be the wound that will never heal. Both diseases are characterised by a long chronic inflammatory pathology, and treatment strategies focuses on immune suppressive drugs that target cytokines and their receptor1, chemical elimination or surgery, although these treatments are not curative. Recently, it was reported that there is a probable connection between cancer, IBD and tissue repair, although the phenotypes of cellular pathology could diverge in some minor details. Nevertheless, the greater challenge remains particularly to target patients who do not respond or who lose response to treatment. To improve therapeutic design and implement new effective treatments of IBD and CRC, it will thus be necessary to increase the knowledge of how intestinal barrier homeostasis is supported by the microenvironment, constituting of stromal cells, and Neuro-Immune units. My future independent research is focused on Enteric Neuro-Immune units (eNIu) as sensors of environmental factors, their role in gut homeostasis (health and disease) and their impact on brain-gut axis physiology. The main aim is to understand how different environments imprint on eNIu to induce inflammation or health/repair, and to identify the local inter- and intra-cellular networks and connections with the central nervous system (CNS). This work will shed light on enteric Neuro-Immune units during IBD, opening new and personalised therapy opportunities for fibrosis associated to resistant IBD or to UC-CRC, and CRC patients.

Keywords:INFLAMMATORY BOWEL DISEASE, BRAIN, IMMUNOLOGY, NERVOUS SYSTEMS

Disciplines:Gastro-enterology, Inflammation, Innate immunity, Cellular interactions and extracellular matrix, Neurophysiology