From conifers to cognition: Microbes, brain and behavior.

A diversity of bacteria, protozoans and viruses ("endozoites") were recently uncovered within healthy tissues including the human brain. By contrast, it was already recognized a century ago that healthy plants tissues contain abundant endogenous microbes ("endophytes"). Taking endophytes as an informative precedent, we overview the nature, prevalence, and role of endozoites in mammalian tissues, centrally focusing on the brain, concluding that endozoites are ubiquitous in diverse tissues. These passengers often remain subclinical, but they are not silent. We address their routes of entry, mechanisms of persistence, tissue specificity, and potential to cause long-term behavioral changes and/or immunosuppression in mammals, where rabies virus is the exemplar. We extend the discussion to Herpesviridae, Coronaviridae, and Toxoplasma, as well as to diverse bacteria and yeasts, and debate the advantages and disadvantages that endozoite infection might afford to the host and to the ecosystem. We provide a clinical perspective in which endozoites are implicated in neurodegenerative disease, anxiety/depression, and schizophrenia. We conclude that endozoites are instrumental in the delicate balance between health and disease, including age-related brain disease, and that endozoites have played an important role in the evolution of brain function and human behavior.