The brain’s Geppetto—microbes as puppeteers of neural function and behaviour?

Research on the microbiome and its interaction with various host organs, including the brain, is increasingly gaining momentum. With more evidence establishing a comprehensive microbiota-gut-brain axis, questions have been raised as to the extent to which microbes influence brain physiology and behaviour. In parallel, there is a growing literature showing active behavioural manipulation in favour of the microbe for certain parasites. However, it seems unclear where the hidden majority of microbes are localised on the parasitism-mutualism spectrum. A long evolutionary history intimately connects host and microbiota, which complicates this classification. In this conceptual minireview, we discuss current hypotheses on host-microbe interaction and argue that novel experimental approaches and theoretical concepts, such as the hologenome theory, are necessary to incorporate transgenerational epigenetic inheritance of the microbiome into evolutionary theories.