AUTHOR=Stilling Roman M., Bordenstein Seth R., Dinan Timothy G., Cryan John F. TITLE=Friends with social benefits: host-microbe interactions as a driver of brain evolution and development? JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=4 YEAR=2014 URL=https://www.frontiersin.org/articles/10.3389/fcimb.2014.00147 DOI=10.3389/fcimb.2014.00147 ISSN=2235-2988 ABSTRACT=The tight association of the human body with trillions of colonizing microbes that we observe today is the result of a long evolutionary history. Only very recently have we started to understand how this symbiosis also affects brain function and behavior. In this hypothesis and theory article, we propose how host-microbe associations potentially influenced mammalian brain evolution and development. In particular, we explore the integration of human brain development with evolution, symbiosis, and RNA biology, which together represent a “social triangle” that drives human social behavior and cognition. We argue that, in order to understand how inter-kingdom communication can affect brain adaptation and plasticity, it is inevitable to consider epigenetic mechanisms as important mediators of genome-microbiome interactions on an individual as well as a transgenerational time scale. Finally, we unite these interpretations with the hologenome theory of evolution. Taken together, we propose a tighter integration of neuroscience fields with host-associated microbiology by taking an evolutionary perspective.