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      Surface components and metabolites of probiotics for regulation of intestinal epithelial barrier

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          Abstract

          The gut microbiota can significantly affect the function of the intestinal barrier. Some intestinal probiotics (such as Lactobacillus, Bifidobacteria, a few Escherichia coli strains, and a new generation of probiotics including Bacteroides thetaiotaomicron and Akkermansia muciniphila) can maintain intestinal epithelial homeostasis and promote health. This review first summarizes probiotics’ regulation of the intestinal epithelium via their surface compounds. Surface layer proteins, flagella, pili and capsular polysaccharides constitute microbial-associated molecular patterns and specifically bind to pattern recognition receptors, which can regulate signaling pathways to produce cytokines or inhibit apoptosis, thereby attenuating inflammation and enhancing the function of the gut epithelium. The review also explains the effects of metabolites (such as secreted proteins, organic acids, indole, extracellular vesicles and bacteriocins) of probiotics on host receptors and the mechanisms by which these metabolites regulate gut epithelial barrier function. Previous reviews summarized the role of the surface macromolecules or metabolites of gut microbes (including both probiotics and pathogens) in human health. However, these reviews were mostly focused on the interactions between these substances and the intestinal mucosal immune system. In the current review, we only focused on probiotics and discussed the molecular interaction between these bacteria and the gut epithelial barrier.

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          The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon.

          The microbiome is being characterized by large-scale sequencing efforts, yet it is not known whether it regulates host metabolism in a general versus tissue-specific manner or which bacterial metabolites are important. Here, we demonstrate that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues. This tissue specificity is due to colonocytes utilizing bacterially produced butyrate as their primary energy source. Colonocytes from germfree mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the TCA cycle. Consequently, there is a marked decrease in NADH/NAD(+), oxidative phosphorylation, and ATP levels, which results in AMPK activation, p27(kip1) phosphorylation, and autophagy. When butyrate is added to germfree colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy. The mechanism is due to butyrate acting as an energy source rather than as an HDAC inhibitor. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4.

            Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed that microbial-specific indoles regulated intestinal barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-α while it upregulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2(-/-)) mice showed a distinctly "leaky" gut physiology coupled with upregulation of the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial barrier were corrected in Nr1i2(-/-)Tlr4(-/-) mice. Our results demonstrate that a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway that involves luminal sensing and signaling by TLR4.
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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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                Author and article information

                Contributors
                zhaiqixiao@sina.com
                Journal
                Microb Cell Fact
                Microb. Cell Fact
                Microbial Cell Factories
                BioMed Central (London )
                1475-2859
                5 February 2020
                5 February 2020
                2020
                : 19
                : 23
                Affiliations
                [1 ]GRID grid.258151.a, ISNI 0000 0001 0708 1323, State Key Laboratory of Food Science and Technology, , Jiangnan University, ; Wuxi, 214122 Jiangsu People’s Republic of China
                [2 ]GRID grid.258151.a, ISNI 0000 0001 0708 1323, School of Food Science and Technology, , Jiangnan University, ; Wuxi, 214122 Jiangsu China
                [3 ]GRID grid.460176.2, ISNI 0000 0004 1775 8598, Wuxi People’s Hospital Affiliated to Nanjing Medical University, ; Wuxi, 214023 Jiangsu People’s Republic of China
                [4 ]GRID grid.258151.a, ISNI 0000 0001 0708 1323, National Engineering Research Center for Functional Food, , Jiangnan University, ; Wuxi, 214122 Jiangsu China
                [5 ]GRID grid.258151.a, ISNI 0000 0001 0708 1323, (Yangzhou) Institute of Food Biotechnology, , Jiangnan University, ; Yangzhou, 225004 China
                [6 ]GRID grid.258151.a, ISNI 0000 0001 0708 1323, International Joint Research Laboratory for Probiotics at Jiangnan University, ; Wuxi, 214122 Jiangsu China
                [7 ]Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi, China
                [8 ]GRID grid.411615.6, ISNI 0000 0000 9938 1755, Beijing Innovation Centre of Food Nutrition and Human Health, , Beijing Technology and Business University (BTBU), ; Beijing, 100048 People’s Republic of China
                Author information
                http://orcid.org/0000-0002-0605-2675
                Article
                1289
                10.1186/s12934-020-1289-4
                7003451
                32024520
                f880bf9b-bec3-45a2-9344-9c3696a52301
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 2 November 2019
                : 20 January 2020
                Funding
                Funded by: National Natural Science Foundation of China Program
                Award ID: 31820103010
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Biotechnology
                probiotic,microbial-associated molecular patterns,metabolites,intestinal epithelial barrier

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