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

Abstract: 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 strong socioeconomic burden on health systems worldwide. Due to the limited success of clinical trials of therapies against neurodegenerative diseases, research has extended its scope to a systems medicine point of view, with a particular focus on the gastrointestinal-brain axis as a potential main actor in disease development and progression. Microbiome as well as metabolome studies along the gastrointestinal-brain axis have already revealed important insights into disease pathomechanisms. Both the microbiome and metabolome can be easily manipulated by dietary and lifestyle interventions, and might thus offer novel, readily available therapeutic options to prevent the onset as well as the progression of PD and AD. This review summarizes our current knowledge on the association between microbiota, metabolites, and neurodegeneration in light of the gastrointestinal-brain axis. In this context, we also illustrate state-of-the art methods of microbiome and metabolome research as well as metabolic modeling that facilitate the identification of disease pathomechanisms. We conclude our review with therapeutic options to modulate microbiome composition to prevent or delay neurodegeneration and illustrate potential future research directions to fight PD and AD.