| Summary: | 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 behaviour. Here 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 behaviour 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.
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