Intestinal barrier permeability, often clinically referred to as “leaky gut,” is the measure of how easily substances can pass through the single-cell layer of the intestinal epithelium and enter the underlying tissues and bloodstream. Optimal permeability allows for the controlled, selective absorption of nutrients and water while strictly preventing the paracellular passage of toxins, undigested food particles, and microorganisms. Dysregulated permeability is a key pathological factor in systemic inflammation, immune dysregulation, and the development of chronic metabolic and hormonal issues.
Origin
The term combines intestinal barrier (the physical and immunological defense layer of the gut) with permeability (the state of being penetrable). Its clinical relevance has grown exponentially with the modern understanding of the gut-immune and gut-endocrine axes, recognizing that a compromised barrier is the initial step in a cascade of inflammatory events. The integrity of this barrier is now a major, actionable focus in functional medicine and longevity research.
Mechanism
The primary mechanism of barrier control resides in the tight junctions, multiprotein complexes that physically seal the microscopic space between adjacent epithelial cells, precisely regulating paracellular transport. Hormones and microbial metabolites, such as zonulin and short-chain fatty acids, actively modulate the structural integrity of these tight junctions. Increased permeability results from the breakdown of these crucial junctions, allowing large, immunogenic molecules to pass through, which then trigger a local and systemic immune response, potentially leading to chronic inflammation and hormonal resistance.
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