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It is noteworthy that Metchnikoff was ahead of his time regarding the microbiome when he added, Systematic investigations should be performed on the relation of intestinal bacteria to premature aging, as well as the impact of diets that avoid intestinal putrefaction in extending life and preserving bodily functions (Metchnikoff, 1907)

Since the first two pathways is mainly related to the concentration difference of intracellular and extracellular solutes rather than a regulatory role of the cell itself, the low permeability of BBB is achieved primarily by the efflux effects of ABCs and the inefficient vesicle transport

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