The intestinal epithelium is a single-cell-thick barrier covering approximately 30 square metres. These cells are connected by tight junction protein complexes (primarily zonulin-regulated) that control paracellular permeability. When tight junction integrity is compromised, luminal content including bacterial fragments, partially digested food antigens, and microbial metabolites enters systemic circulation, where they trigger immune activation.
Reducing Permeability
- L-glutamine — the primary fuel for enterocytes; has RCT evidence for permeability reduction
- Zinc carnosine — shown to stabilise the mucosal barrier in multiple trials
- High-fibre and high-polyphenol diet — feeds Akkermansia and Lactobacillus species that maintain barrier integrity
- Fermented foods — increase the microbial diversity associated with better barrier function
- Avoiding unnecessary NSAIDs — they damage the mucosal layer and increase permeability
leaky gutintestinal permeabilityinflammationautoimmunegut healthtight junctions