| First Author | Xie J | Year | 2023 |
| Journal | EMBO J | Volume | 42 |
| Issue | 17 | Pages | e111515 |
| PubMed ID | 37427561 | Mgi Jnum | J:341268 |
| Mgi Id | MGI:7528621 | Doi | 10.15252/embj.2022111515 |
| Citation | Xie J, et al. (2023) Gut microbiota regulates blood-cerebrospinal fluid barrier function and Abeta pathology. EMBO J 42(17):e111515 |
| abstractText | Accumulating evidence indicates that gut microbiota dysbiosis is associated with increased blood-brain barrier (BBB) permeability and contributes to Alzheimer's disease (AD) pathogenesis. In contrast, the influence of gut microbiota on the blood-cerebrospinal fluid (CSF) barrier has not yet been studied. Here, we report that mice lacking gut microbiota display increased blood-CSF barrier permeability associated with disorganized tight junctions (TJs), which can be rescued by recolonization with gut microbiota or supplementation with short-chain fatty acids (SCFAs). Our data reveal that gut microbiota is important not only for the establishment but also for the maintenance of a tight barrier. Also, we report that the vagus nerve plays an important role in this process and that SCFAs can independently tighten the barrier. Administration of SCFAs in App(NL-G-F) mice improved the subcellular localization of TJs at the blood-CSF barrier, reduced the beta-amyloid (Abeta) burden, and affected microglial phenotype. Altogether, our results suggest that modulating the microbiota and administering SCFAs might have therapeutic potential in AD via blood-CSF barrier tightening and maintaining microglial activity and Abeta clearance. |
