The Gut Microbiota is Important for the Maintenance of Blood-Cerebrospinal Fluid Barrier Integrity.

The gut microbiota communicates with the brain though several pathways including the vagus nerve, immune system, microbial metabolites, and through the endocrine system. Pathways along the humoral/immune gut-microbiota-brain axis comprise of a series of vascular and epithelial barriers including the intestinal epithelial barrier, gut-vascular barrier, blood brain barrier, and blood-cerebrospinal fluid barrier. Of these barriers, the relationship between the gut microbiota and blood-cerebrospinal fluid barrier is yet to be fully defined. Here, using a germ-free mouse model, we aimed to assess the relationship between the gut microbiota and the integrity of the blood-cerebrospinal fluid barrier which is localized to the choroid plexus epithelium. Using confocal microscopy, we visualized the tight junction protein zonula occludens-1, an integral aspect of choroid plexus integrity, as well as the choroid plexus fenestrated capillaries. Quantification of tight junction proteins via network analysis led to the observation that there was a decrease in the zonula occludens-1 network organization in germ-free mice, however, we did not observe any differences in capillary structure. Taken together, these data indicate that the blood- cerebrospinal fluid barrier is another barrier along the gut-microbiota-brain axis. Future studies are required to elucidate its relative contribution in signaling from microbiota to the brain.