Regulation of Physiological Barrier Function by the Commensal Microbiota

A fundamental characteristic of living organisms is their ability to separate the internal and external environments, a function achieved in large part through the different physiological barrier systems and their component junctional molecules. Barrier integrity is subject to multiple influences, but one that has received comparatively little attention to date is the role of the commensal microbiota. These microbes, which represent approximately 50% of the cells in the human body, are increasingly recognized as powerful physiological modulators in other systems, but their role in regulating barrier function is only beginning to be addressed. Through comparison of the impact commensal microbes have on cell–cell junctions in three exemplar physiological barriers—the gut epithelium, the epidermis and the blood–brain barrier—this review will emphasize the important contribution microbes and microbe-derived mediators play in governing barrier function. By extension, this will highlight the critical homeostatic role of commensal microbes, as well as identifying the puzzles and opportunities arising from our steadily increasing knowledge of this aspect of physiology.