The Continuous Mucosal Liquid Layer: A Unified Hypothesis for Airway-Digestive Immune Surveillance, Mucociliary Transport, and Disease Susceptibility

Background: The mucosal surfaces from the anterior nares to the anal canal are lined by a continuous liquid layer studied extensively in regional isolation — as airway surface liquid in pulmonary physiology, gastric mucus in gastroenterology, and nasal mucus in rhinology — but never conceptualized as a unified physiological system. Framework: This paper proposes that this continuous mucosal liquid layer functions as a "mucosal river" serving three critical roles: physical barrier protection, immune transport of secretory immunoglobulins and antimicrobial peptides, and maintenance of the hydrated microenvironment required for commensal microbial homeostasis. Nasal cilia function as the initial pump generating downstream momentum; pharyngeal and digestive peristalsis maintain flow; pulmonary cilia serve as tributary pumps feeding the main channel against gravity. The adenoid crypts function as immunological canyons — narrow, deep channels that use Venturi-effect flow dynamics and M-cell-mediated antigen transport to actively deliver antigen-laden mucus into immune processing centers. Waldeyer's ring forms a 360-degree antigen trap through which the river cannot pass without immune surveillance, and the first breath represents an immunological ignition event initiating adaptive immunity. Hypotheses: The framework generates testable predictions regarding pepsin as a pathologic passenger ascending the river against flow to cause posterior-predominant sinonasal inflammation, systemic dehydration disrupting the river through mucus hyperconcentration and ciliary compression, cigarette smoke damming the river via acquired CFTR dysfunction, and an antibiotic-dehydration "double hit" synergistically compromising mucosal barrier integrity. Each prediction is paired with a specific experimental design for validation. Conclusion: Understanding the mucosal river as a unified system may reshape approaches to chronic inflammatory diseases of the airway and digestive tract.