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      Effects of Exercise on the Oral Microbiota and Saliva of Patients with Non-Alcoholic Fatty Liver Disease

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          Abstract

          Exercise can be hypothesized to play an important role in non-alcoholic fatty liver disease (NAFLD) treatment by changing the oral bacterial flora and in the mechanism underlying periodontal disease. We performed salivary component analysis before and after an exercise regimen, and genome analysis of the oral bacterial flora to elucidate the underlying mechanism. Obese middle-aged men with NAFLD and periodontal disease were allocated to 12-week exercise ( n = 49) or dietary restriction ( n = 21) groups. We collected saliva to compare the oral microflora; performed predictive analysis of metagenomic functions; and, measured the salivary immunoglobulin A, cytokine, bacterial lipopolysaccharide (LPS), and lactoferrin concentrations. The exercise group showed improvements in the clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. Analysis of the microbial composition revealed that the numbers of Campylobacter (+83.9%), Corynebacterium (+142.3%), Actinomyces (+75.9%), and Lautropia (+172.9%) were significantly higher, and that of Prevotella (−28.3%) was significantly lower. The findings suggest that an exercise regimen improves the oral environment of NAFLD patients by increasing the diversity of the oral microflora and reducing the number of periodontal bacteria that produce LPS and its capability.

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          Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences

          Profiling phylogenetic marker genes, such as the 16S rRNA gene, is a key tool for studies of microbial communities but does not provide direct evidence of a community’s functional capabilities. Here we describe PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a computational approach to predict the functional composition of a metagenome using marker gene data and a database of reference genomes. PICRUSt uses an extended ancestral-state reconstruction algorithm to predict which gene families are present and then combines gene families to estimate the composite metagenome. Using 16S information, PICRUSt recaptures key findings from the Human Microbiome Project and accurately predicts the abundance of gene families in host-associated and environmental communities, with quantifiable uncertainty. Our results demonstrate that phylogeny and function are sufficiently linked that this ‘predictive metagenomic’ approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available.
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            Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis.

            Whereas in most cases a fatty liver remains free of inflammation, 10%-20% of patients who have fatty liver develop inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Inflammation may precede steatosis in certain instances. Therefore, NASH could reflect a disease where inflammation is followed by steatosis. In contrast, NASH subsequent to simple steatosis may be the consequence of a failure of antilipotoxic protection. In both situations, many parallel hits derived from the gut and/or the adipose tissue may promote liver inflammation. Endoplasmic reticulum stress and related signaling networks, (adipo)cytokines, and innate immunity are emerging as central pathways that regulate key features of NASH.
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              Data, information, knowledge and principle: back to metabolism in KEGG

              In the hierarchy of data, information and knowledge, computational methods play a major role in the initial processing of data to extract information, but they alone become less effective to compile knowledge from information. The Kyoto Encyclopedia of Genes and Genomes (KEGG) resource (http://www.kegg.jp/ or http://www.genome.jp/kegg/) has been developed as a reference knowledge base to assist this latter process. In particular, the KEGG pathway maps are widely used for biological interpretation of genome sequences and other high-throughput data. The link from genomes to pathways is made through the KEGG Orthology system, a collection of manually defined ortholog groups identified by K numbers. To better automate this interpretation process the KEGG modules defined by Boolean expressions of K numbers have been expanded and improved. Once genes in a genome are annotated with K numbers, the KEGG modules can be computationally evaluated revealing metabolic capacities and other phenotypic features. The reaction modules, which represent chemical units of reactions, have been used to analyze design principles of metabolic networks and also to improve the definition of K numbers and associated annotations. For translational bioinformatics, the KEGG MEDICUS resource has been developed by integrating drug labels (package inserts) used in society.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                26 March 2021
                April 2021
                : 18
                : 7
                : 3470
                Affiliations
                [1 ]Department of Oral and Maxillofacial Surgery, University of Tsukuba Hospital, Tsukuba, Ibaraki 305-8576, Japan; uchiyamada1031@ 123456yahoo.co.jp
                [2 ]Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; ohsechang@ 123456md.tsukuba.ac.jp
                [3 ]Department of Medical Technology and Sciences, International University of Health and Welfare, Narita, Chiba 286-8686, Japan; t-shida@ 123456iuhw.ac.jp
                [4 ]Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; hideoszk@ 123456md.tsukuba.ac.jp (H.S.); yuji-mizokami@ 123456md.tsukuba.ac.jp (Y.M.)
                [5 ]Department of Oral and Maxillofacial Surgery, Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; y-kenji@ 123456md.tsukuba.ac.jp (K.Y.); bukawah-cuh@ 123456umin.ac.jp (H.B.)
                [6 ]Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; tanaka.kiyoji.ft@ 123456u.tsukuba.ac.jp
                Author notes
                [* ]Correspondence: shodaj@ 123456md.tsukuba.ac.jp ; Tel.: +81-29-853-5795
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-1469-7449
                https://orcid.org/0000-0001-7231-7478
                Article
                ijerph-18-03470
                10.3390/ijerph18073470
                8036855
                33810609
                e814e52d-a719-44df-8751-ed3361a20e85
                © 2021 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
                : 19 February 2021
                : 23 March 2021
                Categories
                Article

                Public health
                periodontal disease,non-alcoholic fatty liver disease,exercise,clinical trial,oral microbiota,saliva components

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