Innovations in targeting intestinal immunity for chronic inflammatory disorders - Volume II

The intestinal immune system plays a pivotal role in maintaining mucosal homeostasis, acting as the interface between environmental stimuli, host epithelial barriers, and a vast and diverse microbiota. Recent research has underscored the importance of this system in mediating tolerance to commensal microbes and dietary antigens while facilitating robust defense against pathogens. However, disruption of these finely tuned regulatory networks is a defining feature of chronic inflammatory disorders such as inflammatory bowel disease (IBD), necrotizing enterocolitis, and microscopic colitis. Although classical immune pathways remain central to our understanding, contemporary evidence highlights the critical involvement of metabolic and glycosylation-dependent mechanisms in shaping intestinal immunity. Innovative studies have illuminated the profound impact of microbiota-derived amino acid metabolism and glycan–immune interactions, providing new mechanistic insights into immune homeostasis and disease pathogenesis—yet, how these networks are integrated at the molecular, cellular, and systemic levels remains inadequately understood. Current therapeutic interventions do not deliver lasting remission for many patients, reflecting persistent knowledge gaps and the need for disruptive, mechanism-based approaches.This Research Topic aims to spotlight pioneering advances and novel conceptual frameworks in the targeting of intestinal immunity for chronic inflammatory disorders. Our main objectives are to unravel how immune, metabolic, microbial, and glycosylation pathways are dynamically interconnected to regulate mucosal function, drive inflammation, and mediate therapeutic responses or resistance. We specifically encourage investigations elucidating the crosstalk between immune cells, microbiota-derived metabolites (with special attention to amino acid catabolism), and the “sugar code” of glycan-mediated immune signaling. Through this multidisciplinary lens, we seek to advance the identification of precise diagnostic markers, conceptualize new intervention points, and accelerate the translation of these discoveries from bench to bedside. By bridging discoveries from immunology, microbiology, metabolism, and glycobiology, this collection aspires to inform the next generation of precision diagnostics and therapies for chronic intestinal inflammation.This Research Topic will focus on the multi-layered regulation of gut immunity in health and disease, with particular emphasis on the integration of metabolic, microbial, and glycosylation signals. Contributions may address, but are not limited to, the following themes:-Innate and adaptive immune mechanisms underpinning intestinal homeostasis and inflammation-Interactions between gut epithelium, microbiota, and immune cells during chronic inflammatory states-Microbiota-mediated amino acid metabolism and its impact on mucosal immunity and inflammatory signaling-The roles of tryptophan, arginine, glutamine, and branched-chain amino acids in mucosal disease-Metabolite-driven modulation of key immune signaling axes (e.g., AhR, mTOR, inflammasome, NF-κB)-Glycan-mediated regulation of immune responses and the maintenance of epithelial barrier function-Glycan-binding proteins (e.g., siglecs, galectins, lectins) in intestinal immunity and inflammation-Glycosylation changes in IBD, necrotizing enterocolitis, colorectal cancer, and related disorders-Crosstalk between glycosylation, microbiota, and metabolic pathways shaping mucosal immunity-Immune cell plasticity and metabolic reprogramming in the gut microenvironment-Genetic and environmental factors influencing intestinal immune dysregulation-Mechanisms of action and resistance to immunotherapies, especially at the metabolic and glyco-immune checkpoints-Development of multi-omic biomarkers based on metabolites, glycans, and immune profiles-Next-generation therapeutic strategies targeting the intersection of microbiota, metabolism, glycosylation, and immunity-Application of advanced technologies, such as single-cell omics, spatial transcriptomics, glycomics, and intestinal organoid modelsTo further consolidate knowledge, foster interdisciplinary partnerships, and accelerate innovation, we welcome submissions including original research articles, reviews, and translational studies that address these themes and advance the field toward restoring homeostasis and improving patient outcomes in chronic inflammatory intestinal disorders. Topic editors: Yukihiro Yamaguchi, Keita Nishiyama, Lei Huang Source: https://www.frontiersin.org/research-topics/80067/innovations-in-targeting-intestinal-immunity-for-chronic-inflammatory-disorders---volume-ii