Exercise, diet and stress as modulators of gut microbiota: Implications for neurodegenerative diseases.

The last decade has witnessed an exponentially growing interest in gut microbiota and the gut-brain axis in health and disease. Accumulating evidence from preclinical and clinical research indicate that gut microbiota, and their associated microbiomes, may influence pathogenic processes and thus the onset and progression of various diseases, including neurological and psychiatric disorders. In fact, gut dysbiosis (microbiota dysregulation) has been associated with a range of neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's and motor neuron disease, as well as multiple sclerosis. The gut microbiota constitutes a dynamic microbial system constantly challenged by many biological variables, including environmental factors. Since the gut microbiota constitute a changeable and experience-dependent ecosystem, they provide potential therapeutic targets that can be modulated as new interventions for dysbiosis-related disorders, including neurodegenerative diseases. This article reviews the evidence for environmental modulation of gut microbiota and its relevance to brain disorders, exploring in particular the implications for neurodegenerative diseases. We will focus on three major environmental factors that are known to influence the onset and progression of those diseases, namely exercise, diet and stress. Further exploration of environmental modulation, acting via both peripheral (e.g. gut microbiota and associated metabolic dysfunction or 'metabolopathy') and central (e.g. direct effects on CNS neurons and glia) mechanisms, may lead to the development of novel therapeutic approaches, such as enviromimetics, for a wide range of neurological and psychiatric disorders.