Very pleased to present our latest work on the mechanisms of the gut-brain axis (https://doi.org/10.1101/2022.11.12.516113) and how the blood-brain barrier is affected in chronic kidney disease

Work was led by Sita Shah and co-authors Tobias Knausenberger, Emily Connell, Gwen Le Gall, Tom Hardy, David Randall, Kieran McCafferty, Magdi Yaqoob, Egle Solito, Michael Muller, Andrew Stachulski, Bobby Glen, David Vauzour and @BugsInYourGuts

People with CKD are at increased risk of stroke and brain blood vessel disease, but we don’t really know why. We looked at the role of the gut microbe-derived toxin p-cresol sulfate (pCS)

Using cell and mouse models we show that pCS activates the EGF receptor to cause metalloprotease release, damaging and weakening the blood-brain barrier

Importantly, we also showed that serum from patients undergoing haemodialysis for CKD damaged blood-brain barrier integrity in vitro, an effect we could block by treating with an EGF receptor inhibitor

We think this further highlights the importance of gut microbes in disease, and shows just how interlinked different organ systems are #gutkidneybrainaxis

And maybe EGF receptor inhibitors might be useful in modifying CKD stroke risk?

All of this was made possible by Alzheimer's Research UK awarding us a pilot project grant six years ago. Think we might have got a bit carried away with the amount of #gutbrainaxis work we did with it, but we are incredibly grateful!

#gutbrainaxis #BBB #CKD #cresolsulfate #kidney #gutmicrobiota #uraemia #Alzheimer'sResearchUK