Preclinical evidence strongly suggests a role for the gut microbiome in modulating the host central nervous system function and behavior. Several communication channels have been identified that enable microbial signals to reach the brain and that enable the brain to influence gut microbial composition and function. In rodent models, endocrine, neural, and inflammatory signals generated by gut microbes can alter brain structure and function, while autonomic nervous system activity can affect the microbiome by modulating the intestinal environment and by directly regulating microbial behavior. The amount of information that reaches the brain is dynamically regulated by the blood-brain barrier and the intestinal barrier. In humans, associations between gut microbial composition and function and several brain disorders have been reported, and fecal microbial transplants from patient populations into gnotobiotic mice have resulted in the reproduction of homologous features in the recipient mice. However, in contrast to preclinical findings, there is little information about a causal role of the gut microbiome in modulating human central nervous system function and behavior. Longitudinal studies in large patient populations with therapeutic interventions are required to demonstrate such causality, which will provide the basis for future clinical trials. © 2020 American Physiological Society. Compr Physiol 10:57-72, 2020.
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