A Budding Relationship: Bacterial Extracellular Vesicles in the Microbiota-Gut-Brain Axis.

Sandor Haas-Neill,Paul Forsythe

doi:10.3390/ijms21238899

Abstract

The discovery of the microbiota-gut-brain axis has revolutionized our understanding of systemic influences on brain function and may lead to novel therapeutic approaches to neurodevelopmental and mood disorders. A parallel revolution has occurred in the field of intercellular communication, with the realization that endosomes, and other extracellular vesicles, rival the endocrine system as regulators of distant tissues. These two paradigms shifting developments come together in recent observations that bacterial membrane vesicles contribute to inter-kingdom signaling and may be an integral component of gut microbe communication with the brain. In this short review we address the current understanding of the biogenesis of bacterial membrane vesicles and the roles they play in the survival of microbes and in intra and inter-kingdom communication. We identify recent observations indicating that bacterial membrane vesicles, particularly those derived from probiotic organisms, regulate brain function. We discuss mechanisms by which bacterial membrane vesicles may influence the brain including interaction with the peripheral nervous system, and modulation of immune activity. We also review evidence suggesting that, unlike the parent organism, gut bacteria derived membrane vesicles are able to deliver cargo, including neurotransmitters, directly to the central nervous system and may thus constitute key components of the microbiota-gut-brain axis.

Highlights

The microbiota–gut–brain axis refers to wide-ranging interactions between the gut microbiota and the central nervous system which involve endocrine, immune, and neural signaling pathways [1]
There are numerous studies indicating that the gut microbiota plays a role in development of the central nervous system (CNS) and modulates systems associated with stress responses, anxiety [3,4,5] and memory [1]
Depression and anxiety have been associated with disruption of immune regulation and an inflammatory immune profile [84,85,86] In animal models, immune activation has been linked to changes in anxiety, memory, social behavior, and learning [87,88,89,90,91], and the development of symptoms associated with mood and cognitive disorders [92,93,94,95]

Summary

Introduction

The microbiota–gut–brain axis refers to wide-ranging interactions between the gut microbiota and the central nervous system which involve endocrine, immune, and neural signaling pathways [1]. Commensal bacteria indirectly regulate release of HPA hormones such as cortisol, modifying the stress response and anxiety-like behavior [2,40] This control is achieved through the microbial secretion of short chain fatty acids which are able to diffuse past the intestinal epithelium to induce epigenetic change, as well as bind to G protein coupled receptors: GPR43, GPR41, and GPR109A on the surface of cells to transduce downstream hormone release [41,42]. Neurotransmitters, including serotonin, dopamine, noradrenaline, and GABA, are both indirectly regulated by the presence of certain gut bacteria, and are produced by certain bacteria [45,46,47] Neurotransmitters and their precursors, hormone-like metabolites, and short chain fatty acids are transported or diffuse across the epithelial barrier and into the blood, in which they are carried throughout the body including to the brain where they act on respective receptors to modulate neuronal and microglial function [41,42,43]. Once they are in the blood it is implied that they travel throughout the entire body and may deliver cargo to several organs including the brain

Bacterial MV Modulate Immune Activity

Bacterial MV Stimulate the Local Nervous System

Bacterial MV Carry Psychoactive Cargo