Microbiota‐derived extracellular vesicles in interkingdom communication in the gut

Abstract

The intestine is fundamental in controlling human health. Intestinal epithelial and immune cells are continuously exposed to millions of microbes that greatly impact on intestinal epithelial barrier and immune function. This microbial community, known as gut microbiota, is now recognized as an important partner of the human being that actively contribute to essential functions of the intestine but also of distal organs. In the gut ecosystem, bidirectional microbiota‐host communication does not involve direct cell contacts. Both microbiota and host‐derived extracellular vesicles (EVs) are key players of such interkingdom crosstalk. There is now accumulating body of evidence that bacterial secreted vesicles mediate microbiota functions by transporting and delivering into host cells effector molecules that modulate host signalling pathways and cell processes. Consequently, vesicles released by the gut microbiota may have great influence on health and disease. Here we review current knowledge on microbiota EVs and specifically highlight their role in controlling host metabolism, intestinal barrier integrity and immune training.

Multi-Organ Crosstalk with Endocrine Pancreas: A Focus on How Gut Microbiota Shapes Pancreatic Beta-Cells

“…Interestingly and as was mentioned earlier, the microbiota can produce EVs with different compositions regulating key events in disease progression and in health maintenance [ 92 , 93 ]. In fact, the EVs derived from bacteria are known as microbiota-released extracellular vesicles (MEVs).…”

Biogenesis and Biological Functions of Extracellular Vesicles in Cellular and Organismal Communication With Microbes

“…Processes associated with BEV release include cell wall turnover; physical, salt, or antibiotic-induced stress; lipopolysaccharide and phospholipid remodeling of the outer membrane; and the action of quorum-sensing signal molecules (Díaz-Garrido et al, 2021a). OMVs have been characterized as containing cell wall components, lipopolysaccharides, enzymes and other proteins, and secondary metabolites, as well as DNA molecules and an array of RNA molecules including tRNAs, mRNAs, non-coding RNAs, and fragments of rRNAs (Woith et al, 2019;Munhoz da Rocha et al, 2020;Cai et al, 2021;Díaz-Garrido et al, 2021a). Gram-negative bacteria also produce "outer-inner membrane vesicles" (O-IMVs), likely by similar mechanisms as OMVs.…”

“…Bacteria-derived extracellular vesicles produced by Gramnegative bacteria have been implicated in many aspects of bacterial pathogenicity and proliferation, including nutrient acquisition, stress responses, virulence factor delivery, biofilm formation, and development of antibiotic resistance (Kuehn and Kesty, 2005;Schwechheimer and Kuehn, 2015;Joffe et al, 2016;Toyofuku et al, 2019;Woith et al, 2019;Díaz-Garrido et al, 2021a). Virulence factors delivered by BEVs include alkaline phosphatase, hemolytic phospholipase C and Cif toxin in the case of Pseudomonas aeruginosa (Bomberger et al, 2009) and Shiga toxin 2a, cytolethal distending toxin V and EHEC-hemolysin in the case of enterohemorrhagic Escherichia coli (Bielaszewska et al, 2017).…”

“…BEV cargoes are rich in enzymes such as glycosidases, sulfatases, proteases, and inositol phosphatases that can break down host-indigestible dietary glycans and also host mucins, releasing nutrients such as carbohydrates, short chain fatty acids, and phosphates to both host and microbes. BEVs are also important effectors of the role of the gut microbiome in stimulating the maintenance of the epithelial barrier and providing a healthy ongoing priming of the innate immune system (Díaz-Garrido et al, 2021a). BEVs can also cross the epithelial layer into the body, likely via paracellular diffusion, transcytosis and/or via phagocytotic cells in the mucosal epithelium (Jones et al, 2020;Díaz-Garrido et al, 2021a), with physiological effects that are still being explored.…”

“…by a thick, rigid cell wall, and EVs produced by Gram-positive bacteria consist of cytoplasmic membrane vesicles (CMVs) (Díaz-Garrido et al, 2021a; Table 1 and Figure 1B). Archaeal…”