The article discusses the role of the gut microbiome in regulating epithelial barrier function and its implications for health and disease. The gut epithelial barrier is a complex system that maintains a balance between inward and outward passage of molecules, preventing harmful microorganisms and antigens from entering the body while allowing the absorption of nutrients and water. Increased gut permeability, or "leaky gut," is associated with various diseases, including infections, metabolic disorders, inflammatory and autoimmune diseases, and neurological conditions. The gut microbiome influences gut permeability through various mechanisms, including the production of metabolites that regulate tight junction proteins, which are critical for maintaining barrier function. Factors such as cytokines, dietary components, and the microbiome can affect gut permeability. The article reviews the molecular mechanisms underlying barrier permeability, including the roles of tight junctions, adherens junctions, and desmosomes. It also explores how the microbiome contributes to gut permeability and how this can be harnessed for therapeutic purposes. The role of the microbiome in diseases such as inflammatory bowel disease (IBD), rheumatic diseases, and metabolic disorders is discussed, highlighting the importance of maintaining a healthy gut barrier for overall health. The article also addresses how certain therapies can disrupt the gut epithelial barrier, leading to complications. Overall, the study emphasizes the critical role of the gut microbiome in regulating epithelial barrier function and its potential for therapeutic intervention.The article discusses the role of the gut microbiome in regulating epithelial barrier function and its implications for health and disease. The gut epithelial barrier is a complex system that maintains a balance between inward and outward passage of molecules, preventing harmful microorganisms and antigens from entering the body while allowing the absorption of nutrients and water. Increased gut permeability, or "leaky gut," is associated with various diseases, including infections, metabolic disorders, inflammatory and autoimmune diseases, and neurological conditions. The gut microbiome influences gut permeability through various mechanisms, including the production of metabolites that regulate tight junction proteins, which are critical for maintaining barrier function. Factors such as cytokines, dietary components, and the microbiome can affect gut permeability. The article reviews the molecular mechanisms underlying barrier permeability, including the roles of tight junctions, adherens junctions, and desmosomes. It also explores how the microbiome contributes to gut permeability and how this can be harnessed for therapeutic purposes. The role of the microbiome in diseases such as inflammatory bowel disease (IBD), rheumatic diseases, and metabolic disorders is discussed, highlighting the importance of maintaining a healthy gut barrier for overall health. The article also addresses how certain therapies can disrupt the gut epithelial barrier, leading to complications. Overall, the study emphasizes the critical role of the gut microbiome in regulating epithelial barrier function and its potential for therapeutic intervention.