Microbial-derived metabolites induce actin cytoskeletal rearrangement and protect blood-brain barrier function

Emily G Knox; Maria R Aburto; Carmen Tessier; Jatin Nagpal; Gerard Clarke; Caitriona M O'Driscoll; John F Cryan

doi:10.1016/j.isci.2022.105648

Microbial-derived metabolites induce actin cytoskeletal rearrangement and protect blood-brain barrier function

iScience. 2022 Nov 23;25(12):105648. doi: 10.1016/j.isci.2022.105648. eCollection 2022 Dec 22.

Authors

Emily G Knox^{1

2}, Maria R Aburto^{2

3}, Carmen Tessier², Jatin Nagpal², Gerard Clarke^{2

4}, Caitriona M O'Driscoll¹, John F Cryan^{2

4}

Affiliations

¹ Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland.
² APC Microbiome Ireland, University College Cork, Cork, Ireland.
³ Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
⁴ Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.

Abstract

The gut microbiota influences host brain function, but the underlying gut-brain axis connections and molecular processes remain unclear. One pathway along this bidirectional communication system involves circulating microbially derived metabolites, such as short-chain fatty acids (SCFAs), which include butyrate and propionate. Brain endothelium is the main interface of communication between circulating signals and the brain, and it constitutes the main component of the blood-brain barrier (BBB). Here, we used a well-established in vitro BBB model treated with physiologically relevant concentrations of butyrate and propionate with and without lipopolysaccharide (LPS) to examine the effects of SCFAs on the actin cytoskeleton and tight junction protein structure. Both SCFAs induced distinct alterations to filamentous actin directionality. SCFAs also increased tight junction protein spikes and protected from LPS-induced tight-junction mis-localization, improved BBB integrity, and modulated mitochondrial network dynamics. These findings identify the actin cytoskeletal dynamics as another target further illuminating how SCFAs can influence BBB physiology.

Keywords: Biological sciences; cell biology; functional aspects of cell biology; organizational aspects of cell biology.