The ability of bacterial pathogens to influence behavior has been recognized for decades, most notably bacteria that directly invade the nervous system. However, increasing evidence is mounting that microorganisms may directly interact with elements of the host’s neurophysiological system in a noninvasive manner that ultimately results in modification of host behavior. This ability of microorganisms contained within the microbiome to influence behavior through a noninfectious and possibly non-immunemediated route may be due to their ability to produce and recognize neurochemicals that are exactly analogous in structure to those produced by the host nervous system. This form of interkingdom signaling, which is based on bidirectional neurochemical interactions between the host’s neurophysiological system and the microbiome, was introduced two decades ago and has been termed microbial endocrinology [1]. Many of the neuroendocrine hormone biosynthetic pathways that are more commonly associated with eukaryotic cells are found in prokaryotic cells, and the acquisition of such neurochemical-based synthesis pathways by eukaryotic systems is believed to be due to lateral gene transfer from bacteria. Approaching the microbiome from a microbial endocrinology-based vantage point may provide an understanding of the specific pathways by which microorganisms may influence behavior and thereby lead to new approaches to the treatment of specific mental illness based on modulation of the microbiome-gut-brain axis.

What Is Known—Associations of Microbes with Behavior