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      A metagenome-wide association study of gut microbiota in asthma in UK adults

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          Abstract

          Background

          Asthma, one of the most common chronic respiratory disorders, is associated with the hyper-activation of the T-cell subset of adaptive immunity. The gut microbiota may be involved in the development of asthma through the production of short-chain fatty acids (SCFAs), exhibiting modulatory effects on Th. So, we performed a metagenome-wide association study (MWAS) of the fecal microbiota from individuals with asthma and healthy controls. And that was the first case to resolve the relationship between asthma and microbiome among UK adults.

          Results

          The microbiota of the individuals with asthma consisted of fewer microbial entities than the microbiota of healthy individuals. Faecalibacterium prausnitzii, Sutterella wadsworthensis and Bacteroides stercoris were depleted in cases, whereas Clostridiums with Eggerthella lenta were over-represented in individuals with asthma. Functional analysis shows that the SCFAs might be altered in the microbiota of asthma patients.

          Conclusion

          In all, the adult human gut microbiome of asthma patients is clearly different from healthy controls. The functional and taxa results showed that the change of asthma patients might related to SCFAs.

          Electronic supplementary material

          The online version of this article (10.1186/s12866-018-1257-x) contains supplementary material, which is available to authorized users.

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          Most cited references13

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          Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease.

          Specific members of the intestinal microbiota dramatically affect inflammatory bowel disease (IBD) in mice. In humans, however, identifying bacteria that preferentially affect disease susceptibility and severity remains a major challenge. Here, we used flow-cytometry-based bacterial cell sorting and 16S sequencing to characterize taxa-specific coating of the intestinal microbiota with immunoglobulin A (IgA-SEQ) and show that high IgA coating uniquely identifies colitogenic intestinal bacteria in a mouse model of microbiota-driven colitis. We then used IgA-SEQ and extensive anaerobic culturing of fecal bacteria from IBD patients to create personalized disease-associated gut microbiota culture collections with predefined levels of IgA coating. Using these collections, we found that intestinal bacteria selected on the basis of high coating with IgA conferred dramatic susceptibility to colitis in germ-free mice. Thus, our studies suggest that IgA coating identifies inflammatory commensals that preferentially drive intestinal disease. Targeted elimination of such bacteria may reduce, reverse, or even prevent disease development. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut.

            The human gut is home to trillions of microbes, thousands of bacterial phylotypes, as well as hydrogen-consuming methanogenic archaea. Studies in gnotobiotic mice indicate that Methanobrevibacter smithii, the dominant archaeon in the human gut ecosystem, affects the specificity and efficiency of bacterial digestion of dietary polysaccharides, thereby influencing host calorie harvest and adiposity. Metagenomic studies of the gut microbial communities of genetically obese mice and their lean littermates have shown that the former contain an enhanced representation of genes involved in polysaccharide degradation, possess more archaea, and exhibit a greater capacity to promote adiposity when transplanted into germ-free recipients. These findings have led to the hypothesis that M. smithii may be a therapeutic target for reducing energy harvest in obese humans. To explore this possibility, we have sequenced its 1,853,160-bp genome and compared it to other human gut-associated M. smithii strains and other Archaea. We have also examined M. smithii's transcriptome and metabolome in gnotobiotic mice that do or do not harbor Bacteroides thetaiotaomicron, a prominent saccharolytic bacterial member of our gut microbiota. Our results indicate that M. smithii is well equipped to persist in the distal intestine through (i) production of surface glycans resembling those found in the gut mucosa, (ii) regulated expression of adhesin-like proteins, (iii) consumption of a variety of fermentation products produced by saccharolytic bacteria, and (iv) effective competition for nitrogenous nutrient pools. These findings provide a framework for designing strategies to change the representation and/or properties of M. smithii in the human gut microbiota.
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              The genetics of asthma and allergic disease: a 21st century perspective.

              Asthma and allergy are common conditions with complex etiologies involving both genetic and environmental contributions. Recent genome-wide association studies (GWAS) and meta-analyses of GWAS have begun to shed light on both common and distinct pathways that contribute to asthma and allergic diseases. Associations with variation in genes encoding the epithelial cell-derived cytokines, interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), and the IL1RL1 gene encoding the IL-33 receptor, ST2, highlight the central roles for innate immune response pathways that promote the activation and differentiation of T-helper 2 cells in the pathogenesis of both asthma and allergic diseases. In contrast, variation at the 17q21 asthma locus, encoding the ORMDL3 and GSDML genes, is specifically associated with risk for childhood onset asthma. These and other genetic findings are providing a list of well-validated asthma and allergy susceptibility genes that are expanding our understanding of the common and unique biological pathways that are dysregulated in these related conditions. Ongoing studies will continue to broaden our understanding of asthma and allergy and unravel the mechanisms for the development of these complex traits. © 2011 John Wiley & Sons A/S.
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                Author and article information

                Contributors
                wangqi1@genomics.cn
                lifei1@genomics.cn
                709880442@qq.com
                liangyuhu@genomics.cn
                Chen.3428@buckeyemail.osu.edu
                moxiaodong@cngb.org
                juyanmei@genomics.cn
                zhaohui1@genomics.cn
                jiahuijue@genomics.cn
                tim.spector@kcl.ac.uk
                guoruijin@genomics.cn
                Journal
                BMC Microbiol
                BMC Microbiol
                BMC Microbiology
                BioMed Central (London )
                1471-2180
                12 September 2018
                12 September 2018
                2018
                : 18
                : 114
                Affiliations
                [1 ]BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083 China
                [2 ]ISNI 0000 0001 2034 1839, GRID grid.21155.32, BGI-Shenzhen, ; Shenzhen, 518083 China
                [3 ]ISNI 0000 0001 2034 1839, GRID grid.21155.32, China National Genebank, , BGI-Shenzhen, ; Shenzhen, 518083 China
                [4 ]Macau University of Science and Technology, Taipa, Macau, 999078 China
                [5 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Department of Twin Research and Genetic Epidemiology, , King’s College London, ; London, SE1 7EH UK
                [6 ]GRID grid.416466.7, Department of Oncology, , Nanfang Hospital, Southern Medical University, ; Guangzhou, Guangdong 510515 People’s Republic of China
                [7 ]ISNI 0000 0001 2034 1839, GRID grid.21155.32, Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, , BGI-Shenzhen, ; Shenzhen, 518083 China
                Author information
                http://orcid.org/0000-0001-7863-3797
                Article
                1257
                10.1186/s12866-018-1257-x
                6134768
                30208875
                2c06c974-6223-4be1-8bf1-1964817d5084
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.

                History
                : 25 February 2018
                : 4 September 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 105022/Z/14/Z
                Award Recipient :
                Funded by: Shenzhen Municipal Government of China
                Award ID: JSGG20140702161403250, DRC-SZ [2015]162, CXB201108250098A, JSGG20160229172752028, and JCYJ20160229172757249
                Award Recipient :
                Funded by: Science and Technology Development
                Award ID: 077/ 2014/A2
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Microbiology & Virology
                asthma,mwas,eggerthella lenta,faecalibacterium prausnitzii,scfas
                Microbiology & Virology
                asthma, mwas, eggerthella lenta, faecalibacterium prausnitzii, scfas

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