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.
Davies et al. (2026) studied this question.