Mental health and gut-brain crosstalk: implications for depression and Alzheimer's disease

Brain health and mental health disorders are increasingly becoming an essential priority for modern societies as they affect different parameters of life, such as brain health, quality of life, and productivity with a heavy societal and economic burden. Among mental health disorders, depression and Alzheimer disease (AD) have the higher impact on mental health globally as they are highly prevalent, cause long-term cognitive and mood deficits while they are deeply interconnected, with chronic stress raising as a risk factor and potential link between both disorders. This review focuses on the gut-brain axis, a bidirectional communication network that links the gut microbiome with the central nervous system, and its role in brain malfunction and pathology related to stress, depression and AD. This intricate gut-brain crosstalk is orchestrated through top-down and bottom-up mechanisms implicating the HPA axis, the enteric nervous system as well as gut microbiota-derived metabolites, neurotransmitters, epigenetic processes and extracellular vesicles/exosomes that can contribute to depression and AD. The current work provides a comprehensive summary of evidence linking gut microbial alterations to these brain pathologies, with particular focus on lifestyle and nutrition (e.g. food, water) as critical regulators. Lastly, we explore the therapeutic potential of microbiome-targeted interventions including pro/pre/post-biotics, and trace elements (e.g. lithium and silicon). Overall, this review highlights the potential of microbiome-centered strategies as novel interventions to support mental health and wellbeing.