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      Gut Microbiome of Indonesian Adults Associated with Obesity and Type 2 Diabetes: A Cross-Sectional Study in an Asian City, Yogyakarta

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          Abstract

          Indonesia is a developing country facing the national problem of the growing obesity and diabetes in its population due to recent drastic dietary and lifestyle changes. To understand the link between the gut microbiome, diet, and health of Indonesian people, fecal microbiomes and metabolomes of 75 Indonesian adults in Yogyakarta City, including obese people ( n = 21), type 2 diabetes (T2D) patients ( n = 25), and the controls ( n = 29) were characterized together with their dietary and medical records. Variations of microbiomes showed a triangular distribution in the principal component analysis, driven by three dominant bacterial genera, namely Bacteroides, Prevotella, and Romboutsia. The Romboutsia-driven microbiome, characterized by low bacterial diversity and high primary bile acids, was associated with fat-driven obesity. The Bacteroides-driven microbiome, which counteracted Prevotella but was associated with Ruminococcaceae concomitantly increased with high-carbohydrate diets, showed positive correlation with T2D indices but negative correlation with body mass index. Notably, Bacteroides fragilis was increased in T2D patients with a decrease in fecal conjugated bile acids, particularly tauroursodeoxycholic acid (TUDCA), a farnesoid X receptor (FXR) antagonist with anti-diabetic activity, while these features disappeared in patients administered metformin. These results indicate that the gut microbiome status of Indonesian adults is differently associated with obesity and T2D under their varied dietary habits.

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          Metagenomic biomarker discovery and explanation

          This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.
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            UPARSE: highly accurate OTU sequences from microbial amplicon reads.

            Amplified marker-gene sequences can be used to understand microbial community structure, but they suffer from a high level of sequencing and amplification artifacts. The UPARSE pipeline reports operational taxonomic unit (OTU) sequences with ≤1% incorrect bases in artificial microbial community tests, compared with >3% incorrect bases commonly reported by other methods. The improved accuracy results in far fewer OTUs, consistently closer to the expected number of species in a community.
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              A metagenome-wide association study of gut microbiota in type 2 diabetes.

              Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                22 April 2021
                May 2021
                : 9
                : 5
                : 897
                Affiliations
                [1 ]Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan; vo_21851@ 123456hotmail.com (P.T.); lana745143663@ 123456gmail.com (Y.S.); msr456852@ 123456gmail.com (M.T.)
                [2 ]Faculty of Agricultural Technology, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia; maria_slimshady@ 123456yahoo.com (M.M.); almunifah@ 123456gmail.com (M.A.); nancyekaputri@ 123456gmail.com (N.E.P.M.); siskaindriarsih@ 123456gmail.com (S.I.); endangsrahayu@ 123456ugm.ac.id (E.S.R.)
                [3 ]Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan; ly22999@ 123456hotmail.com (Y.L.); aknagata@ 123456mail.ecc.u-tokyo.ac.jp (K.N.)
                [4 ]Material Management Center of Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan; kfukami@ 123456mmc.kyushu-u.ac.jp
                [5 ]Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; t-ikeda@ 123456surg2.med.kyushu-u.ac.jp
                [6 ]Endoscopy and Endoscopic Surgery, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan
                [7 ]Department of Microbiology and Immunology, National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore; micleeyk@ 123456nus.edu.sg
                Author notes
                [* ]Correspondence: nakayama@ 123456agr.kyushu-u.ac.jp ; Tel.: +81-92-802-4737
                Author information
                https://orcid.org/0000-0001-7875-4265
                https://orcid.org/0000-0002-4704-0603
                Article
                microorganisms-09-00897
                10.3390/microorganisms9050897
                8147061
                33922321
                4d19e018-c16a-4755-b965-2958ada11466
                © 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 ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 27 March 2021
                : 20 April 2021
                Categories
                Article

                gut microbiome,bile acids,dietary habits,obesity,type 2 diabetes

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