Intestinal Permeability (Leaky Gut)
Toxin and bacterial leakage through the gut barrier compromises immunity
Definition
Increased intestinal permeability — colloquially known as 'leaky gut' — is the loss of integrity of the intestinal epithelial barrier, which normally acts as a selective filter between the gut lumen and systemic circulation. When tight junctions between enterocytes weaken, they allow passage of bacterial fragments (LPS), undigested food proteins, and toxins into circulation, activating low-grade systemic inflammation. Although controversial in conventional medicine, there is solid molecular evidence in coeliac disease, inflammatory bowel disease, and MAFLD.
Detailed explanation
Alessio Fasano (Harvard) identified zonulin as the main regulator of tight junctions. Elevated serum zonulin correlates with increased intestinal permeability and has been associated with coeliac disease, type 1 diabetes, schizophrenia, autism, MS, and obesity. Factors that increase zonulin and permeability are: wheat gliadin, intestinal dysbiosis, alcohol, chronic NSAIDs, infections, chronic stress, extreme endurance exercise (marathons), chemotherapy, and radiotherapy.
Pathological mechanism (metabolic endotoxemia): when bacterial LPS cross the intestinal epithelium, they reach the liver via the portal vein, activating hepatic macrophages (Kupffer cells) → IL-6 and TNF-α production → systemic inflammation → insulin resistance, MAFLD, neuroinflammation. This LPS-inflammation axis is implicated in several disorders.
Clinical measurement: lactulose/mannitol test (urine, elevated ratio indicates permeability), serum or stool zonulin, biomarkers of bacterial translocation (sCD14, LPS-binding protein, anti-LPS antibodies).
Interventions to restore barrier integrity: temporary elimination of gliadin/gluten (30-day test to detect reactives), L-glutamine (5-10 g/day — preferred enterocyte fuel), zinc carnosine, polyphenols (curcumin, quercetin), butyrate (postbiotic or supplementation), spermidine (intestinal autophagy), selective prebiotics, and, in severe cases, elimination diet with guided reintroduction.
Scientific sources
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