Microbial Endocrinology in the Microbiome-Gut-Brain Axis: How Bacterial Production and Utilization of Neurochemicals Influence Behavior

Mark Lyte,Virginia Miller

doi:10.1371/journal.ppat.1003726

Abstract

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-immune-mediated 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.

Highlights

The ability of bacterial pathogens to influence behavior has been recognized for decades, most notably bacteria that directly invade the nervous system
The role of neuroendocrine hormones, especially those biogenic amines related to the stress response, in the pathogenesis of infectious disease has become increasingly recognized following the first reports in the early 1990s that documented the ability of catecholamines to directly stimulate bacterial growth and alter virulence factor production [11]
These initial studies led to the proposal of the field of microbial endocrinology, which in effect represents the intersection of host neurophysiology with the microbiome in which neuroendocrine-bacterial interactions are a governing mechanism

Summary

Introduction

The ability of bacterial pathogens to influence behavior has been recognized for decades, most notably bacteria that directly invade the nervous system. The neuroendocrine hormone norepinephrine is found in plants, as well as in insects and fish, and most critically from the standpoint of microbiologists, in microbes [9] Due to these same shared biochemical pathways, the Citation: Lyte M (2013) Microbial Endocrinology in the Microbiome-Gut-Brain Axis: How Bacterial Production and Utilization of Neurochemicals Influence Behavior. The role of neuroendocrine hormones, especially those biogenic amines related to the stress response, in the pathogenesis of infectious disease has become increasingly recognized following the first reports in the early 1990s that documented the ability of catecholamines to directly stimulate bacterial growth and alter virulence factor production [11] These initial studies led to the proposal of the field of microbial endocrinology, which in effect represents the intersection of host neurophysiology with the microbiome in which neuroendocrine-bacterial interactions are a governing mechanism (for review, see [12]). Synthesis of benzodiazepine receptor ligands by gut bacteria can contribute to the development of encephalopathy that can accompany fulminant hepatic failure by accumulating in the brain and enhancing GABAergic transmission [14]

Moving beyond Infection to Host Behavior

Microbial Endocrinology as a Central and Unifying Mechanism