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      The gut microbiome of healthy Japanese and its microbial and functional uniqueness

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          Abstract

          The human gut microbiome has profound influences on the host's health largely through its interference with various intestinal functions. As recent studies have suggested diversity in the human gut microbiome among human populations, it will be interesting to analyse how gut microbiome is correlated with geographical, cultural, and traditional differences. The Japanese people are known to have several characteristic features such as eating a variety of traditional foods and exhibiting a low BMI and long life span. In this study, we analysed gut microbiomes of the Japanese by comparing the metagenomic data obtained from 106 Japanese individuals with those from 11 other nations. We found that the composition of the Japanese gut microbiome showed more abundant in the phylum Actinobacteria, in particular in the genus Bifidobacterium, than other nations. Regarding the microbial functions, those of carbohydrate metabolism were overrepresented with a concurrent decrease in those for replication and repair, and cell motility. The remarkable low prevalence of genes for methanogenesis with a significant depletion of the archaeon Methanobrevibacter smithii and enrichment of acetogenesis genes in the Japanese gut microbiome compared with others suggested a difference in the hydrogen metabolism pathway in the gut between them. It thus seems that the gut microbiome of the Japanese is considerably different from those of other populations, which cannot be simply explained by diet alone. We postulate possible existence of hitherto unknown factors contributing to the population-level diversity in human gut microbiomes.

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          Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease.

          To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. The effect of SCFAs on cytokine release from human neutrophils was studied with ELISA. SCFA-dependent modulation of NF-kappaB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFalpha release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-kappaB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-kappaB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.
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            The gut microbiota of rural papua new guineans: composition, diversity patterns, and ecological processes.

            Although recent research revealed an impact of westernization on diversity and composition of the human gut microbiota, the exact consequences on metacommunity characteristics are insufficiently understood, and the underlying ecological mechanisms have not been elucidated. Here, we have compared the fecal microbiota of adults from two non-industrialized regions in Papua New Guinea (PNG) with that of United States (US) residents. Papua New Guineans harbor communities with greater bacterial diversity, lower inter-individual variation, vastly different abundance profiles, and bacterial lineages undetectable in US residents. A quantification of the ecological processes that govern community assembly identified bacterial dispersal as the dominant process that shapes the microbiome in PNG but not in the US. These findings suggest that the microbiome alterations detected in industrialized societies might arise from modern lifestyle factors limiting bacterial dispersal, which has implications for human health and the development of strategies aimed to redress the impact of westernization.
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              The microbiome of uncontacted Amerindians

              Most studies of the human microbiome have focused on westernized people with life-style practices that decrease microbial survival and transmission, or on traditional societies that are currently in transition to westernization. We characterize the fecal, oral, and skin bacterial microbiome and resistome of members of an isolated Yanomami Amerindian village with no documented previous contact with Western people. These Yanomami harbor a microbiome with the highest diversity of bacteria and genetic functions ever reported in a human group. Despite their isolation, presumably for >11,000 years since their ancestors arrived in South America, and no known exposure to antibiotics, they harbor bacteria that carry functional antibiotic resistance (AR) genes, including those that confer resistance to synthetic antibiotics and are syntenic with mobilization elements. These results suggest that westernization significantly affects human microbiome diversity and that functional AR genes appear to be a feature of the human microbiome even in the absence of exposure to commercial antibiotics. AR genes are likely poised for mobilization and enrichment upon exposure to pharmacological levels of antibiotics. Our findings emphasize the need for extensive characterization of the function of the microbiome and resistome in remote nonwesternized populations before globalization of modern practices affects potentially beneficial bacteria harbored in the human body.
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                Author and article information

                Journal
                DNA Res
                DNA Res
                dnares
                dnares
                DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
                Oxford University Press
                1340-2838
                1756-1663
                April 2016
                06 March 2016
                06 March 2016
                : 23
                : 2
                : 125-133
                Affiliations
                [1 ]Graduate School of Frontier Sciences, The University of Tokyo , Chiba 277-8561, Japan
                [2 ]Department of Microbiology and Immunology, Keio University School of Medicine , Tokyo 160-8582, Japan
                [3 ]RIKEN Center for Integrative Medical Sciences , Kanagawa 230-0045, Japan
                [4 ]Electronics-Inspired Interdisciplinary Research Institute, Toyohashi University of Technology , Aichi 441-8580, Japan
                [5 ]Graduate School of Environmental and Life Science, Okayama University , Okayama 700-8530, Japan
                [6 ]Graduate School of Advanced Science and Engineering, Waseda University , Tokyo 169-8555, Japan
                Author notes
                [* ]To whom correspondence should be addressed. Tel. +81 4-7136-4070. Fax. +81 4-7136-4084. Email: m-hattori@ 123456aoni.waseda.jp

                Edited by Dr Katsumi Isono

                Article
                dsw002
                10.1093/dnares/dsw002
                4833420
                26951067
                547e8fca-51c3-4e73-afc1-a61454a7cabd
                © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 30 December 2015
                : 20 January 2016
                Funding
                Funded by: JSPS Fellows
                Award ID: 267812
                Funded by: Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
                Funded by: Azabu University
                Funded by: Core Research for Evolutional Science and Technology (CREST)
                Funded by: Japan Science and Technology Agency (JST)
                Funded by: University of Tokyo http://dx.doi.org/10.13039/501100004721
                Categories
                Full Papers

                Genetics
                microbiome,gut,metagenome,japanese
                Genetics
                microbiome, gut, metagenome, japanese

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