Systemic Leaky Barrier Syndrome (SLBS): A Systems-Level Framework for Chronic Disease

Systemic Leaky Barrier Syndrome (SLBS) is a conceptual framework in which loss of integrity across multiple biological barriers — intestinal, vascular, blood–brain, pulmonary, renal, and skin — is driven by shared structural, metabolic, and inflammatory mechanisms. This hypothesis unifies disparate chronic diseases and aging processes by focusing on common upstream drivers (oxidative stress, micronutrient insufficiency, mitochondrial dysfunction, and chronic inflammation) that impair tight junctions and cell–matrix adhesion across tissues. SLBS reframes chronic disease not as isolated organ dysfunction, but as systemic failure of barrier integrity, with clinical implications for early detection, prevention, and integrative therapeutic strategies. This framework also has implications for cancer progression, where invasion and metastasis require coordinated failure of multiple host barrier systems.