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Mukherjee, A. (2026). Gut barrier integrity and systemic immunity: Mechanisms linking microbiota, barrier dysfunction, and extra-intestinal disease. Clinical Immunology Communications, 9, 121–132. 
Added by: Dr. Enrique Feoli (13/08/2026, 18:57)   Last edited by: Dr. Enrique Feoli (13/08/2026, 19:34)
Resource type: Journal Article
Published
DOI: 10.1016/j.clicom.2026.04.003
ID no. (ISBN etc.): 2772-6134
BibTeX citation key: Mukherjee2026
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Categories: BioAcyl Corp
Subcategories: Gut-origin Sepsis
Keywords: Barrier dysfunction, Extra-intestinal immune disorders, Gut barrier integrity, Microbiota-derived metabolites, Microbiota-immune axis, Systemic immunity
Creators: Mukherjee
Collection: Clinical Immunology Communications
Views: 45/45
Abstract
The intestinal barrier represents a dynamic interface integrating microbial, epithelial, and immune components to maintain host microbiota symbiosis and systemic immune homeostasis. Beyond its classical protective role, the gut barrier has emerged as a key regulator of extra-intestinal immunity. Structural elements such as epithelial tight junctions and mucus layers, together with biological defenses including antimicrobial peptides, secretory immunoglobulin A, and resident immune cells, coordinate to limit microbial translocation while enabling beneficial microbial signaling. Perturbations in this barrier often driven by microbial dysbiosis, environmental factors, or chronic inflammation can permit the systemic dissemination of microbial products and metabolites, thereby reshaping immune signaling networks. Increasing evidence links such barrier dysfunction to the pathogenesis of diverse extra-intestinal conditions, including autoimmune and inflammatory diseases, infections, and cancer. This review synthesizes emerging mechanistic insights into microbiota barrier immune interactions and highlights therapeutic strategies aimed at restoring gut barrier integrity to recalibrate systemic immune responses.
Added by: Dr. Enrique Feoli  Last edited by: Dr. Enrique Feoli
Notes

 

Multi-layered organization of the gut barrier and its systemic immunoregulatory integration- (A) Host systemic context- The intestinal barrier is positioned within a broader host physiological network linking the gut to distal organs, including the brain, liver, and peripheral immune system. This bidirectional communication framework, mediated through neural, metabolic, and immune pathways, establishes the gut as a central regulator of systemic homeostasis. (B) Commensal microbiota and metabolite signaling- The luminal compartment harbors diverse commensal microbial communities that generate bioactive metabolites, including short-chain fatty acids (SCFAs), bile acid derivatives, and tryptophan metabolites. These microbial products modulate epithelial function, immune cell differentiation, and inflammatory tone, thereby contributing to host–microbiota symbiosis. (C) Mucus layer and antimicrobial defense- The mucus barrier, organized into inner and outer layers, provides a critical physical and biochemical shield that limits direct microbial contact with epithelial cells. This layer is enriched with antimicrobial peptides and secretory factors that selectively regulate microbial composition and spatial organization. (D) Epithelial barrier integrity- A single layer of intestinal epithelial cells, interconnected by tight junction proteins (e.g., claudins, occludins, and ZO-1), forms a selectively permeable barrier. This structure enables controlled nutrient absorption while restricting translocation of luminal antigens and microbial components. Epithelial cells also actively participate in immune signaling through cytokine and chemokine secretion. (E) Mucosal immune compartment- The underlying immune network comprises dendritic cells, macrophages, and IgA-producing plasma cells, which collectively mediate immune surveillance, antigen sampling, and tolerance induction. Cytokine signaling pathways, including regulatory mediators such as transforming growth factor-β (TGF-β), contribute to maintaining immune equilibrium and preventing excessive inflammation. (F) Gut-driven systemic regulation.


Added by: Dr. Enrique Feoli  Last edited by: Dr. Enrique Feoli
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