Lipid-derived Microbial Metabolites in Intestinal Barrier Function and Immune Signaling

The intestinal epithelium is not only a physical barrier but also a metabolically responsive interface where microbial signals are translated into epithelial and immune responses. Increasing attention has focused on microbial metabolites as mediators of host–microbiota communication. Among these, lipid-derived microbial metabolites—including secondary bile acids, microbially modified fatty acids, and other lipid mediators produced through host–microbiota metabolic interactions—represent a particularly intriguing class of signaling molecules capable of influencing epithelial stress responses, permeability regulation, and mucosal immune activity. Emerging studies suggest that these compounds may contribute both to the maintenance of barrier homeostasis and to early disturbances in epithelial function associated with low-grade inflammation and disease development. However, their precise roles in epithelial signaling networks and the regulation of barrier function remain incompletely understood, highlighting the need for integrative physiological and translational research in this area.This Research Topic aims to advance a physiology- and pathology-oriented perspective on how lipid-derived microbial metabolites influence intestinal epithelial function and immune signaling. Despite increasing recognition of microbial metabolites as mediators of host–microbiota communication, their roles in epithelial permeability regulation, barrier integrity, and mucosal immune responses remain incompletely integrated across disciplines. The focus is therefore on understanding how these metabolites act as signaling mediators within host–microbiota interactions. By bringing together studies from physiology, microbiology, immunology, and translational research, this collection seeks to highlight mechanistic insights into how lipid-derived microbial metabolites shape epithelial function and contribute to barrier homeostasis or dysfunction. It further aims to bridge experimental and clinically relevant perspectives, promoting a clearer understanding of how host–microbiota metabolic interactions influence intestinal health and early disease processes.This Research Topic welcomes contributions examining how lipid-derived microbial metabolites influence intestinal epithelial physiology, barrier regulation, and immune signaling within host–microbiota interactions. Particular interest lies in studies addressing the following themes:-Mechanistic roles of lipid-derived microbial metabolites (e.g., secondary bile acids, microbially modified fatty acids, and related lipid mediators) in regulating epithelial permeability and barrier integrity.-Signaling pathways through which these metabolites modulate epithelial stress responses and mucosal immune signaling.-The contribution of lipid-derived microbial metabolites to low-grade inflammation and early disturbances of intestinal barrier function-Cellular and molecular mechanisms linking microbial lipid metabolites to epithelial–immune communication in the intestinal mucosa-Diet–microbiota interactions shaping the production and signaling of lipid-derived microbial metabolites-Translational and clinical studies investigating how lipid-derived microbial metabolites relate to intestinal barrier function, early disease processes, or extraintestinal conditions linked to gut barrier dysfunctionWe welcome original research articles and review papers employing experimental, mechanistic, or translational approaches. Studies using cellular models, ex vivo intestinal systems, animal models, or human cohorts are particularly encouraged when they provide insight into how microbial lipid metabolites influence epithelial and immune signaling pathways relevant to barrier regulation. Topic editors: Evangelia Kerezoudi, Lorena Ortega Moreno, Laura López-Gómez Source: https://www.frontiersin.org/research-topics/79479/lipid-derived-microbial-metabolites-in-intestinal-barrier-function-and-immune-signaling