Intestinal epithelial injury and systemic inflammatory crosstalk: Gut–organ axis mechanisms

The intestinal epithelium functions as both a selective physical barrier and an active immunological interface that coordinates local and systemic immune homeostasis. Disruption of this barrier is increasingly recognized as a critical event in the initiation and amplification of inflammation beyond the gastrointestinal tract. Following mucosal injury, epithelial repair programs are activated to restore barrier integrity and tissue function. However, when these regenerative responses are impaired or dysregulated, local inflammation may persist, microbial products may translocate, and inflammatory signals may disseminate to distant organs through gut–organ axes.This Research Topic highlights intestinal epithelial health as a central regulator of whole-body immune homeostasis. We aim to move beyond single-pathway models and encourage studies that integrate epithelial repair, cytokine signaling, microbial metabolites, immune-cell regulation, and stem-cell biology to maintain mucosal integrity and limit systemic inflammation. Growing evidence links epithelial barrier dysfunction to disease processes in the lung, liver, brain, and other organs through the gut-lung, gut-liver, and gut-brain axes. By focusing on the transition from mucosal damage to systemic disease, this section seeks to uncover the mechanisms by which the gut drives multi-organ inflammatory pathology.We welcome mechanistic, translational, and clinical studies that examine the gut as a systemic driver of inflammatory disease. Contributions may include, but are not limited to:- Cytokine-Mediated Repair and Signaling: Studies defining how cytokine networks regulate epithelial regeneration, barrier restoration, and the balance between localized and systemic inflammation.- SCFAs and Microbial Metabolites: Research investigating how short-chain fatty acids and other microbiota-derived metabolites support epithelial integrity, shape immune responses, and signal to distant organs.- Mechanisms of Systemic Propagation: Studies mapping how gut inflammation, microbial products, metabolites, and immune mediators spread beyond the mucosa to influence the gut-lung, gut-liver, gut-brain, and other organ axes.- Metabolic-Immune Homeostasis: Work exploring how epithelial barrier function, microbiota-derived metabolic cues, and immune regulation interact to prevent chronic systemic inflammatory states.- Novel Therapeutic Targets: Studies evaluating pharmacological, nutritional, microbiome-based, or cytokine-targeted strategies to restore epithelial barrier function and limit multi-organ inflammatory progression.We invite Original Research, Reviews, Mini Reviews, and Perspective articles from investigators working across immunology, gastroenterolog, microbiome science, epithelial biology, and organ-specific disease fields. This collection aims to advance an integrated understanding of how intestinal epithelial dysfunction drives systemic inflammatory disease and to identify new opportunities for therapeutic intervention. Studies that are unrelated to immunity or immune-related mechanisms of inflammation (e.g. studies on microbiota without a focus on immunity) are out of scope for this section. Topic editors: Xiao Wang, STEFANIA MARZOCCO Source: https://www.frontiersin.org/research-topics/86094/intestinal-epithelial-injury-and-systemic-inflammatory-crosstalk-gut-organ-axis-mechanisms