Ex vivo application of gut microbiota–derived postbiotics in human paediatric cortical tissue

The gut–brain axis (GBA) has been proposed as a modulator of early neurodevelopment, with growing evidence showing that the gut microbiota influences central nervous system (CNS) functions during infancy and childhood. Postbiotic — non-viable microbial products, metabolites, and structural components — represent a promising therapeutic strategy for modulating neuroimmune interactions and supporting brain health. However, it remains challenging to directly assess their effects on the human paediatric brain.This methodological paper describes an efficient protocol to produce and apply gut microbiota-derived postbiotics to ex vivo human paediatric cortical slices. This approach provides a valuable experimental platform to further investigate the direct effects of microbiota-derived factors on human brain circuits, particularly in the context of neurodevelopment and neuroinflammation. Paediatric cortical tissue obtained from patients with drug-resistant epilepsy provides a valuable ex vivo model for assessing postbiotic effects in pathological contexts. Challenges and future directions in standardizing postbiotic-based interventions for neurodevelopmental and neuroimmune disorders are also discussed.