Friends with social benefits: host-microbe interactions as a driver of brain evolution and development?

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.

Keywords: epigenetics; evo-devo; gene-environment interactions; microbiota; neurodevelopment; non-coding RNA; sociality; transgenerational.

Figure 1

Friends with benefits: Social group living and transmission of microbes. Advantages of living in groups may occur through horizontal transfer of beneficial symbionts that increase abilities to digest a wider range of foods (left) or confer resistance against infectious agents (right). Protection from parasites was suggested to be especially important for non-herbivores, where beneficial microbes create a healthy homeostatic microenvironment and train the immune system of the host. The acquired microbes can further be transmitted vertically to the next generation, strengthening the symbiotic association between host and microbe and conferring increased biological fitness.

Figure 2

Microbes, RNA networks and brain development: A social triangle? An integrated model is proposed for the evolution of human social behavior. Recent human evolution was accompanied by accelerated extension of the neocortex along with an increase in the importance of ncRNAs and RNA diversity, processing and plasticity in the brain. At the same time host-microbe co-evolution contributed to enhance sociability by providing endosymbiotic developmental signals through the microbiota-gut-brain axis. In addition, social behavior affects the composition of the microbiota and vice-versa and differential expression of ncRNAs has been observed in cognitive disorders that are associated with altered social behavior (black arrow heads). Whether the microbiota and the brain's transcriptome interact, especially on the level of non-coding RNAs, is currently under investigation.

Figure 3

The epigenetic trio: RNA, DNA and Chromatin modifications. The molecular epigenetic machinery is comprised of DNA, chromatin modifications and several RNA-based mechanisms, most importantly various species of non-coding RNA. Together these mechanisms orchestrate developmental and gene expression patterns. They form a regulatory network, with significant interaction and mutual influences between the different domains (black arrows).