Cerebrovascular damage caused by the gut microbe/host co-metabolite p-cresol sulfate is prevented by blockade of the EGF receptor.

ABSTRACT: The gut microbiota-brain axis has been associated with the pathogenesis of numerous disorders, but the mechanism(s) underlying these links are generally poorly understood. Accumulating evidence indicates the involvement of gut microbe-derived metabolites. Circulating levels of the gut microbe/host co-metabolite p-cresol sulfate (pCS) correlate with cerebrovascular event risk in individuals with chronic kidney disease (CKD), but whether this relationship is mechanistic is unclear. We hypothesized that pCS would impair the function of the blood-brain barrier (BBB), the primary brain vasculature interface. We report that pCS exposure impairs BBB integrity in human cells in vitro and both acutely (≤6 hours) and chronically (28 days) in mice, enhancing tracer extravasation, disrup

SUBMITTER: Shah SN 

PROVIDER: S-EPMC11591591 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature