Microbial endocrinology: Host-microbiota neuroendocrine interactions influencing brain and behavior

Mark Lyte, Mark Lyte

Abstract

The ability of microorganisms, whether present as commensals within the microbiota or introduced as part of a therapeutic regimen, to influence behavior has been demonstrated by numerous laboratories over the last few years. Our understanding of the mechanisms that are responsible for microbiota-gut-brain interactions is, however, lacking. The complexity of the microbiota is, of course, a contributing factor. Nonetheless, while microbiologists approaching the issue of microbiota-gut-brain interactions in the behavior well recognize such complexity, what is often overlooked is the equal complexity of the host neurophysiological system, especially within the gut which is differentially innervated by the enteric nervous system. As such, in the search for common mechanisms by which the microbiota may influence behavior one may look for mechanisms which are shared by both host and microbiota. Such interkingdom signaling can be found in the shared production of neurochemical mediators that are found in both eukaryotes and prokaryotes. The study of the production and recognition of neurochemicals that are exactly the same in structure to those produced in the vertebrate organisms is known as microbial endocrinology. The examination of the microbiota from the vantage point of host-microbiota neuroendocrine interactions cannot only identify new microbial endocrinology-based mechanisms by which the microbiota can influence host behavior, but also lead to the design of interventions in which the composition of the microbiota may be modulated in order to achieve a specific microbial endocrinology-based profile beneficial to overall host behavior.

Keywords: behavior; enteric nervous system; hormones; microbial endocrinology; neuroendocrine; signaling.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4153777/bin/gmic-5-381-g1.jpg
Figure 1. The microbial endocrinology-based pathways by which neuroactive compounds produced by both the host and the microbiota can serve as a mechanism by which the brain and behavior can be modulated within the microbiota-gut-brain axis. Food ingested by the host contains both the substrates needed for neurochemical production by the host and the microbiota as well as fully functional neuroactive components (1). The microbiota in the gut is capable of either forming neurochemicals from the substrates present in the ingested food; or responding to the neuroactive food components themselves; or responding to neurochemicals secreted into the gut by components of the host enteric nervous system (2). Neurochemicals produced by the microbiota in the gut have two pathways by which to influence the host; they can either be taken up from the gut into the portal circulation (3) or they can directly interact with receptors found on components of the enteric nervous system which innervates the complete length of the gastrointestinal tract (2). Once in the portal circulation, microbiota-derived neurochemicals can influence components of the nervous system and ultimately the brain (4). Microbiota-derived neurochemicals can also influence components of the nervous system such as the brain through enteric nervous system-central nervous system communication (5). The result of either pathway (4) or (5) on the brain may result in an alteration of behavior or cognition (6) as well as food preferences and appetite (7)., As described in the text, this should not be viewed as a one-way direction of only gut-to-brain since the brain may influence the composition of the microbiota through the specific release of neurochemicals into the gut lumen (2).

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