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      The Immunomodulatory Properties of Extracellular Vesicles Derived from Probiotics: A Novel Approach for the Management of Gastrointestinal Diseases

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          Abstract

          Probiotics, included in functional foods, nutritional supplements, or nutraceuticals, exhibit different beneficial effects on gut function. They are extensively used to improve the digestive processes as well as reduce the symptoms and progression of different diseases. Probiotics have shown to improve dysbiosis and modulate the immune response of the host by interacting with different cell types. Probiotics and the host can interact in a direct way, but it is becoming apparent that communication occurs also through extracellular vesicles (EVs) derived from probiotics. EVs are key for bacteria–bacteria and bacteria–host interactions, since they carry a wide variety of components that can modulate different signaling pathways, including those involved in the immune response. Interestingly, EVs are recently starting to be considered as an alternative to probiotics in those cases for which the use of live bacteria could be dangerous, such as immunocompromised individuals or situations where the intestinal barrier is impaired. EVs can spread through the mucus layer and interact with the host, avoiding the risk of sepsis. This review summarizes the existing knowledge about EVs from different probiotic strains, their properties, and their potential use for the prevention or treatment of different gastrointestinal diseases.

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          A microbial symbiosis factor prevents intestinal inflammatory disease.

          Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.
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            Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens.

            How can probiotic bacteria transduce their health benefits to the host? Bacterial cell surface macromolecules are key factors in this beneficial microorganism-host crosstalk, as they can interact with host pattern recognition receptors (PRRs) of the gastrointestinal mucosa. In this Review, we highlight the documented signalling interactions of the surface molecules of probiotic bacteria (such as long surface appendages, polysaccharides and lipoteichoic acids) with PRRs. Research on host-probiotic interactions can benefit from well-documented host-microorganism studies that span the spectrum from pathogenicity to mutualism. Distinctions and parallels are therefore drawn with the interactions of similar molecules that are presented by gastrointestinal commensals and pathogens.
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              Probiotics and the gut microbiota in intestinal health and disease.

              The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases. While a growing number of well-conducted, prospective, randomized, controlled, clinical trials are emerging and investigations of underlying mechanisms of action are being undertaken, questions remain with respect to the specific immune and physiological effects of probiotics in health and disease. This Review considers recent advances in clinical trials of probiotics for intestinal disorders in both adult and pediatric populations. An overview of recent in vitro and in vivo research related to potential mechanisms of action of various probiotic formulations is also considered.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                09 May 2019
                May 2019
                : 11
                : 5
                : 1038
                Affiliations
                [1 ]CIBER-EHD, Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, Avenida del Conocimiento s/n 18071-Granada, Spain; jalbertomolinatijeras@ 123456gmail.com (J.A.M.-T.); merodri@ 123456ugr.es (M.E.R.-C.)
                [2 ]Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada 18012, Spain
                Author notes
                [* ]Correspondence: jgalvez@ 123456ugr.es ; Tel.: +34-958-241-793; Fax: +34-958-248-964
                Author information
                https://orcid.org/0000-0001-6876-3782
                Article
                nutrients-11-01038
                10.3390/nu11051038
                6567093
                31075872
                e88ccf5a-4d5d-48fd-b432-2d75cb750f5e
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 March 2019
                : 07 May 2019
                Categories
                Review

                Nutrition & Dietetics
                extracellular vesicles,probiotics,gastrointestinal diseases,microbiota,tlr signaling,tight junctions

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