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Key Messages Intestinal paracellular permeability accounts for the movement of ions and small solutes between the intestinal lumen and the circulation through intercellular tight junctions Studies of the intestinal paracellular transport of large molecules, particulates, and bacteria investigated in cultured epithelially derived cells have to a large extent not been replicated in living organisms Intestinal permeability implying transport through intercellular tight junctions is only one component of the intestinal barrier. The two terms should be used precisely and not interchangeably Many exotoxigenic pathogenic enteric bacteria disrupt the structure and function of the tight junctions, resulting in massive fluid secretion and diarrhea It is unlikely that endotoxin enters the circulation via the paracellular route in undamaged intestinal mucosa M-cells are the most probable entry point of luminal bacteria into the submucosal lymphatics The common assumption that bacterial endotoxins or intact bacteria are transported through the intestine via the paracellular pathway in health or disease is not supported by data obtained in vivo or in vitro in intact mucosa The concept of the leaky gut should be broadened to encompass pathways other than paracellular permeability in the genesis of diseases attributed to endotoxemia References Nagpal R, Yadav H

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