Diet–Immune Crosstalk in the Gut: Nutrient Sensing, Barrier Function, and Inflammatory Outcomes

Diet is increasingly recognized as a central regulator of immune homeostasis through its capacity to shape gut microbial communities, generate bioactive metabolites, and directly influence host immune and epithelial responses. These interactions are particularly critical during sensitive developmental windows and disease-prone states. Early-life nutrition profoundly impacts postnatal immune maturation by directing microbial colonization and immune education, with diet-induced perturbations during infancy and childhood predisposing individuals to long-term autoimmune, metabolic, and inflammatory disease risk. In adulthood, dietary components continue to modulate gut bacteria–immune interactions, whereby balanced microbial ecosystems support immune tolerance, while dysbiosis promotes aberrant inflammatory responses, as exemplified in inflammatory bowel disease (IBD) and other chronic inflammatory conditions linked to nutrition and immune dysregulation. Moreover, Western dietary patterns rich in calories, fat, and refined sugars drive chronic low-grade inflammation (metaflammation) by altering microbial ecology, nutrient-sensing pathways, epithelial barrier integrity, and immune activation, thereby contributing to the growing global burden of non-communicable diseases.Microbial metabolites, including short-chain fatty acids derived from dietary fiber fermentation,bile acid derivatives, and tryptophan-derived indole have emerged as key molecular mediators linking diet to local and systemic immunity. These metabolites regulate epithelial barrier function, innate and adaptive immune responses, cytokine signaling, and immune cell development, including hematopoiesis in the bone marrow, while also influencing distal organ immunity along the gut–lung and gut–brain axes. Collectively, accumulating evidence positions dietary regulation of the microbiota–immune network as a unifying mechanism governing mucosal and systemic immune balance, offering promising opportunities for nutritional, microbial, and immunometabolic interventions.Despite substantial progress over recent decades, significant gaps remain in our mechanistic understanding of how specific nutrients, dietary patterns, and microbial metabolites orchestrate immune responses in health and disease- particularly in (i) clarifying how specific foods, dietary ingredients, and natural products modulate innate and adaptive immune pathways; (ii) mapping cell-type- and tissue-specific nutrient-sensing and immunometabolic programs using single-cell and spatial approaches; and (iii) defining diet–microbiome–metabolite signatures associated with inflammation trajectories and therapeutic response in human cohorts and controlled interventions. . Moreover, current therapeutic strategies, particularly in chronic inflammatory gut disorders, often fail to achieve durable remission across diverse patient populations. Addressing these challenges will require innovative experimental approaches and cross-disciplinary integration from nutrition, immunology, microbiology, gastroenterology, and translational medicine to translate mechanistic insights into effective, personalized interventions.This Research Topic aims to highlight recent advances and emerging concepts in diet-immune crosstalk within the gut, with a particular focus on nutrient sensing, epithelial barrier function, and inflammatory outcomes. By fostering cross-disciplinary contributions, this Research Topic seeks to provide a comprehensive and integrative perspective on immune–nutrient interactions in intestinal health and disease. Emphasis will be placed on cutting-edge methodologies, including single-cell and spatial omics, organoid and ex vivo models, and microbiome- and diet-based therapeutic strategies, which hold promise for advancing precision medicine in gut immunology.We welcome original research articles, reviews, and perspectives addressing, but not limited to, the following themes:-Innate and adaptive immune mechanisms underlying nutrient-driven regulation of intestinal homeostasis and inflammation-Interactions among dietary components, gut epithelium, microbiota, and immune cells in inflammatory disorders-Nutrient-mediated modulation of mucosal immunity and its impact on health and disease-Mechanisms by which nutrients influence responsiveness or resistance to immunotherapies in intestinal diseases- Microbial metabolite classes beyond (e.g., SCFA, bile acids, indoles, polyamines) as regulators of epithelial and immune function- Functional foods, and nutritional supplements that modulate immune responses and barrier function- Specific dietary patterns and interventions (e.g., Mediterranean-style, high-fiber/fermentable fiber, low-FODMAP) and their effects on mucosal immunity and intestinal inflammationThis topic aims to consolidate emerging findings, stimulate interdisciplinary dialogue, and accelerate the development of innovative strategies to restore intestinal immune balance and improve outcomes for patients with inflammatory gut disorders and other related diet-sensitive immune-mediated conditions Topic editors: Yukihiro Yamaguchi, Dhirendra Kumar Singh, Lei Huang Source: https://www.frontiersin.org/research-topics/78753/diet-immune-crosstalk-in-the-gut-nutrient-sensing-barrier-function-and-inflammatory-outcomes