In vitro models of microbiota-gut-brain axis communication at the blood-brain barrier interface

Date

2026

Authors

Davies, M.R.
Cross, C.B.
Aburto, M.R.
Cryan, J.F.
Wardill, H.R.

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Journal of Cerebral Blood Flow and Metabolism, 2026; 1-20

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Maya R Davies, Courtney B Cross, María Rodriguez Aburto, John F Cryan and Hannah R Wardill

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Abstract

Microbiota-gut-brain axis dysfunction is increasingly implicated in the development of various neuropathologies. The blood-brain barrier (BBB) serves as a critical interface between the central nervous system (CNS) and the systemic milieu, modulated by the gut microbiota and associated secretome. Increasingly, the therapeutic potential of microbial metabolites, such as short-chain fatty acids (SCFAs), in reducing BBB disruption and mitigating neuropathologies across multiple neurological conditions has been explored. However, research methodologies remain inconsistent, owing to a lack of clarity on how to effectively model microbiota-gut-brain interactions at the BBB interface. In order to fully realise the potential of the microbiota-gut-brain axis it is crucial to adopt best-practice study designs alongside ongoing advancements in biotechnology that enable more biologically relevant modelling of this complex system. In this review, we examine current knowledge on the role of the BBB in mediating microbiota-gut-brain interactions and explore both established and emerging methods used to study these processes.

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© The Author(s) 2026. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).

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