Regulation of Tight Junction Permeability by Intestinal Bacteria and Dietary Components

Abstract

"The human intestinal epithelium is formed by a single layer of epithelial cells that separates the intestinal lumen from the underlying lamina propria. The space between these cells is sealed by tight junctions (TJ), which regulate the permeability of the intestinal barrier. TJ are complex protein structures comprised of transmembrane proteins, which interact with the actin cytoskeleton via plaque proteins. Signaling pathways involved in the assembly, disassembly, and maintenance of TJ are controlled by a number of signaling molecules, such as protein kinase C, mitogen-activated protein kinases, myosin light chain kinase, and Rho GTPases. The intestinal barrier is a complex environment exposed to many dietary components and many commensal bacteria. Studies have shown that the intestinal bacteria target various intracellular pathways, change the expression and distribution of TJ proteins, and thereby regulate intestinal barrier function. The presence of some commensal and probiotic strains leads to an increase in TJ proteins at the cell boundaries and in some cases prevents or reverses the adverse effects of pathogens. Various dietary components are also known to regulate epithelial permeability by modifying expression and localization of TJ proteins."

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Beyond the Paleolithic prescription: incorporating diversity and flexibility in the study of human diet evolution.

Abstract

"Evolutionary paradigms of human health and nutrition center on the evolutionary discordance or "mismatch" model in which human bodies, reflecting adaptations established in the Paleolithic era, are ill-suited to modern industrialized diets, resulting in rapidly increasing rates of chronic metabolic disease. Though this model remains useful, its utility in explaining the evolution of human dietary tendencies is limited. The assumption that human diets are mismatched to the evolved biology of humans implies that the human diet is instinctual or genetically determined and rooted in the Paleolithic era. This review looks at current research indicating that human eating habits are learned primarily through behavioral, social, and physiological mechanisms that start in utero and extend throughout the life course. Adaptations that appear to be strongly genetic likely reflect Neolithic, rather than Paleolithic, adaptations and are significantly influenced by human niche-constructing behavior. Several examples are used to conclude that incorporating a broader understanding of both the evolved mechanisms by which humans learn and imprint eating habits and the reciprocal effects of those habits on physiology would provide useful tools for structuring more lasting nutrition interventions."

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