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      Microbiota‐derived extracellular vesicles in interkingdom communication in the gut

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          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.

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          Most cited references219

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          Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

          ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
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            Biofilms: an emergent form of bacterial life.

            Bacterial biofilms are formed by communities that are embedded in a self-produced matrix of extracellular polymeric substances (EPS). Importantly, bacteria in biofilms exhibit a set of 'emergent properties' that differ substantially from free-living bacterial cells. In this Review, we consider the fundamental role of the biofilm matrix in establishing the emergent properties of biofilms, describing how the characteristic features of biofilms - such as social cooperation, resource capture and enhanced survival of exposure to antimicrobials - all rely on the structural and functional properties of the matrix. Finally, we highlight the value of an ecological perspective in the study of the emergent properties of biofilms, which enables an appreciation of the ecological success of biofilms as habitat formers and, more generally, as a bacterial lifestyle.
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              Metabolic endotoxemia initiates obesity and insulin resistance.

              Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, respectively, on a nutritional basis and that a 4-week high-fat diet chronically increased plasma LPS concentration two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat-fed mice. In addition, adipose tissue F4/80-positive cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet-induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.
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                Author and article information

                Contributors
                lbaldoma@ub.edu
                Journal
                J Extracell Vesicles
                J Extracell Vesicles
                10.1002/(ISSN)2001-3078
                JEV2
                Journal of Extracellular Vesicles
                John Wiley and Sons Inc. (Hoboken )
                2001-3078
                04 November 2021
                November 2021
                : 10
                : 13 ( doiID: 10.1002/jev2.v10.13 )
                : e12161
                Affiliations
                [ 1 ] Secció de Bioquímica i Biología Molecular, Departament de Bioquímica i Fisiologia Facultat de Farmàcia i Ciències de l'Alimentació Universitat de Barcelona Barcelona Spain
                [ 2 ] Institut de Recerca Sant Joan de Déu (IRSJD) Institut de Biomedicina de la Universitat de Barcelona (IBUB) Barcelona Spain
                Author notes
                [*] [* ] Correspondence

                Laura Baldomà, Secció de Bioquímica i Biología Molecular, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Barcelona, Spain.

                Email: lbaldoma@ 123456ub.edu

                Author information
                https://orcid.org/0000-0003-1220-015X
                https://orcid.org/0000-0003-0768-5033
                https://orcid.org/0000-0002-7678-269X
                Article
                JEV212161
                10.1002/jev2.12161
                8568775
                34738337
                5849f0ca-4d8c-42a4-b6c4-3aa94ef863a4
                © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 30 September 2021
                : 25 May 2021
                : 06 October 2021
                Page count
                Figures: 5, Tables: 1, Pages: 29, Words: 22829
                Funding
                Funded by: Ministerio de Ciencia e Innovación, Gobierno de España
                Award ID: PID2019‐107327RB‐100
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                November 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.8 mode:remove_FC converted:05.11.2021

                bacterial membrane vesicles,gut microbiota,gut permeability,immune regulation,intestinal homeostasis,probiotics

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