Advances in Inflammatory Bowel Disease: Mucosal Defense Mechanisms Against Gut Inflammation.

The delicate balance between immune tolerance and responsiveness in the intestine has its 1 foundation in the synergistic action of multi-layered mucosal defense mechanisms regulating 2 microbiota composition, epithelial integrity, and lamina propria immunity. In the last decades there 3 have been an increasing number of remarkable developments in understanding how mucosal 4 mechanisms regulate intestinal homeostasis, powerfully contributing to the identification of new 5 pharmacological strategies for the treatment of Crohn's disease (CD) and ulcerative colitis (UC), 6 collectively known as inflammatory bowel diseases (IBD). IBD are chronic and relapsing 7 conditions, negatively affecting quality of life of both adult and pediatric patients. Thus, studying 8 molecular targets able to clarify disease etiology and predisposition is crucial for early diagnosis, 9 life-style modifications and therapeutic interventions aimed at improving prognosis and minimizing 10 life-threatening complications. This series of articles has been collected for the Frontiers in 11 Pharmacology journal readership with the aim of showing some of the most recent developments 12 in gut pathophysiology. 13 14 Smith and Creagh discuss the current literature in the area of caspase-4/-5/-11 expression and 15 function in the gut and their role in the inflammation and pathogenesis of IBD 16 affects extra-intestinal organs including the liver and growing evidence on the liver-gut axis suggest 35 a potential association of chronic intestinal inflammation with certain liver diseases with various 36 degrees of fibrosis. Liu and colleagues study the effect of tormentic acid in a rat model of liver 37 fibrosis and, using transcriptomic and metabolomics analysis, find that this herbal ingredient ameliorates liver pathology by inhibiting the glycerophospholipid metabolism, the PI3K/Akt/mTOR 1 and the NF-κB signaling pathways (https://doi.org/10.3389/fphar.2022.801982). 2 3 Our understanding of immune defense mechanisms at the intestinal barrier level and the discovery 4 of promising new potential molecules for the treatment of IBD is not summarizable in one research 5 topic, however we believe that this article collection contributes to an accessible, continue and in-6 depth comprehension of gut mucosal immunology. 7