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

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.

Role of Postbiotics in Diabetes Mellitus: Current Knowledge and Future Perspectives

“…Additionally, they can communicate with the host through microbe- and pathogen-associated molecular patterns (MAMP and PAMP, respectively), leading to an immunomodulatory action. The GM is a good source of EVs that move beyond the intestine and disseminate to other organs and tissues [ 44 , 99 ]. Furthermore, host cells also secrete EVs and recent evidence suggests that they could also play a role in the development and progression of T1D and T2D [ 100 , 101 ].…”

“…The GM is probably the major source of postbiotic constituents. Our resident microbes release a myriad of products, including metabolites and also cell components (reviewed in detail in [ 43 ]), that behave as messengers in the microbiota–host interactions and are of major significance to the host [ 44 , 45 ]. In the present review, however, we focus on the potential of exogenous factors that are orally administered.…”

Role of Microbiota-Derived Extracellular Vesicles in Gut-Brain Communication

“…Furthermore, gut microbiota can themselves release metabolites including neurotransmitters such as serotonin, dopamine, noradrenaline and GABA. These neurotransmitters and their precursors, hormone-like metabolites and short-chain fatty acids can travel through the circulation to the brain where they can act on respective receptors modulating neuronal and microglial functions [35]. In this gut-brain communication, endocrine pathways also participate such as enteroendocrine cells and the hypothalamic-pituitary-adrenal axis.…”

Membrane vesicles of Lacticaseibacillus rhamnosus JB-1 contain immunomodulatory lipoteichoic acid and are endocytosed by intestinal epithelial cells

“…Similarly, we have previously shown that the gram-positive bacterium Lacticaseibacillus rhamnosus JB-1 (JB-1; recently reclassified from Lactobacillus 15 and previously misclassified as L. reuteri 16 ) and its MV can promote the number and functions of regulatory T cells, activate TLR2, and induce an immunoregulatory phenotype in dendritic cells (DCs) 17 – 19 . Substantial evidence now exists that MV from beneficial bacteria can independently influence the host 20 , though their mechanisms of action in many cases remain unclear.…”