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Due to the aging of the world population and westernization of lifestyles,the prevalence of neurodegenerative diseases such as Alzheimer's disease (AD)and Parkinson's disease (PD) is rapidly rising and is expected to put a strongsocioeconomic burden on health systems worldwide. Due to the limited success ofclinical trials of therapies against neurodegenerative diseases, research hasextended its scope to a systems medicine point of view, with a particular focuson the gastrointestinal-brain axis as a potential main actor in diseasedevelopment and progression. Microbiome as well as metabolome studies along thegastrointestinal-brain axis have already revealed important insights intodisease pathomechanisms. Both the microbiome and metabolome can be easilymanipulated by dietary and lifestyle interventions, and might thus offer novel,readily available therapeutic options to prevent the onset as well as theprogression of PD and AD. This review summarizes our current knowledge on theassociation between microbiota, metabolites, and neurodegeneration in light ofthe gastrointestinal-brain axis. In this context, we also illustratestate-of-the art methods of microbiome and metabolome research as well asmetabolic modeling that facilitate the identification of diseasepathomechanisms. We conclude our review with therapeutic options to modulatemicrobiome composition to prevent or delay neurodegeneration and illustratepotential future research directions to fight PD and AD.

Microbiome and metabolome insights into the role of the  gastrointestinal-brain axis in neurodegenerative diseases: unveiling  potential therapeutic targets