One consequence of a progressively ageing global population, is the increasing worldwide prevalence of age-related cognitive decline and dementias.
In the absence of effective therapeutic interventions, identifying risk factors associated with cognitive decline becomes increasingly vital. Novel perspectives suggest that a dynamic bidirectional communication system between the gut, its microbiome, & the central nervous system may be a contributing factor for cognitive health and disease.
The exact mechanisms remain as yet undefined however. Microbial-derived metabolites, produced in the gut, can cross the intestinal epithelial barrier, enter systemic circulation and trigger physiological responses both directly and indirectly, affecting the central nervous system & it’s functions. Dysregulation of this system (dysbiosis) can modulate cytotoxic metabolite production, promote neuroinflammation & negatively impact cognition.
In this review, we explore critical connections between microbial-derived metabolites (secondary bile acids, trimethylamine-N-oxide (TMAO), tryptophan derivatives & others) & their influence upon cognitive function & neurodegenerative disorders, with a particular interest in their less-explored role as risk factors of cognitive decline.

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