Influence of blood-brain barrier and intestinal barrier on microglial phenotypes: a perspective of clinical and prognostic implications

Microglia are highly specialized immune cells of the central nervous system (CNS). These cells exhibit remarkable plasticity, enabling them to adopt distinct phenotypes and functional profiles in response to changes in their microenvironment. Biological barriers, such as the blood-brain barrier (BBB) and the intestinal barrier, play a crucial role in maintaining the organism's homeostasis, protecting organs and tissues against pathogens, toxins, and other external factors. Alterations in the permeability of the BBB and the intestinal barrier expose microglia to peripheral molecules, such as cytokines, LPS, and bacterial metabolites. These molecules reach the CNS via systemic circulation, activating microglia through Toll-Like Receptor (TLR) and Nod-like receptor family pyrin domain-containing (NLRP) receptors and lead to a transition in microglial phenotype. Elucidating bidirectional communication between these barriers and microglia holds significant potential for developing novel therapeutic targets, particularly in neurological disorders with limited treatment options. In this perspective, we discuss how alterations in the BBB and intestinal barrier affect microglial phenotypes, contributing to the development of neurological disorders.