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The link between epithelial permeability and pain likely reflects the abovementioned redundancy of the system involving the gut microbiota overstimulating the immune system through a leaky IEB, leading to the release of immune mediators, such as histamine, tryptase, serotonin, polyunsaturated fatty acids (12-hydroperoxyeicosatetraenoic acid, 15-hydroxyeicosatetraenoic acid, 5-hydroxyeicosatetraenoic acid, 5-oxoeicosatetraenoic acid, and leukotriene B4) (235, 236) known to evoke sensory afferent over-stimulation and pain (230)

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