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      Integrative Analysis Toward Different Glucose Tolerance-Related Gut Microbiota and Diet

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          Abstract

          Objective: There is evidence that type 2 diabetes (T2DM) is affected by gut microbiota, and gut microbiota diversity modified by diet. To investigate its modifications in Uyghur patients with different glucose tolerance, we enrolled 561 subjects: newly diagnosed T2DM ( n = 145), impaired glucose regulation (IGR) patients ( n = 138) and in normal control (NC) population ( n = 278).

          Methods: The nutrient intake in food frequency questionnaire was calculated by R language. The regions V3-V4 of 16S ribosomal RNA were sequenced by using Illumina Miseq platform. Sequences were clustered by operational taxonomy units, gut microbiota composition, and diversity was analyzed. Correlations between bacterial composition at different level and dietary factors were evaluated.

          Results: The α-diversity was highest in NC, followed by T2DM and IGR; β-diversity distinguished between patients and NC. Compared to NC, Saccharibacteria was significantly increased in T2DM and IGR. Deferribacteres was significantly increased in T2DM compared to NC and IGR. Veillonella, Pasteurellaceae, and Haemophilus were over-represented in IGR. Abundance of Bacteroidetes was negatively correlated with LDL-C; Abundance of Tenericutes was negatively correlated with hip circumference and total cholesterol, positively correlated with HDL-C and cake intake; Actinobacteria was positively correlated with BMI and folic acid intake, negatively correlated with oil intake. Firmicutes was negatively correlated with beverage and alcohol intake. Spirochaetae was negatively correlated with fungus, fruits, beans, vitamin C, dietary fiber, and calcium. Fusobacteria was positively correlated with beans intake, and was negatively correlated with fat intake. Proteobacteria was positively correlated with tuber crops intake. Synergistetes was positively correlated with cholesterol, nicotinic acid, and selenium intake. Deferribacteres was negatively correlated with magnesium intake.

          Conclusions: At the phylum and genus level, the structure and diversity of intestinal microbiota of T2DM and IGR was altered, the number of OTUs, the relative abundance, and diversity were all decreased. The gut microbiota of the newly diagnosed T2DM, IGR, and NC were related to age, blood lipids, BMI, blood pressure, and dietary nutrient intake. Unbalanced nutrient intake in the three groups may affect the structure and abundance of the gut microbiota, which may play a role in the occurrence and development of T2DM.

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          Most cited references29

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          Antibiotic-Induced Changes in the Intestinal Microbiota and Disease.

          The gut microbiota is a key player in many physiological and pathological processes occurring in humans. Recent investigations suggest that the efficacy of some clinical approaches depends on the action of commensal bacteria. Antibiotics are invaluable weapons to fight infectious diseases. However, by altering the composition and functions of the microbiota, they can also produce long-lasting deleterious effects for the host. The emergence of multidrug-resistant pathogens raises concerns about the common, and at times inappropriate, use of antimicrobial agents. Here we review the most recently discovered connections between host pathophysiology, microbiota, and antibiotics highlighting technological platforms, mechanistic insights, and clinical strategies to enhance resistance to diseases by preserving the beneficial functions of the microbiota.
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            Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA.

            The human gut microflora is important in regulating host inflammatory responses and in maintaining immune homeostasis. The cellular and molecular bases of these actions are unknown. Here we describe a unique anti-inflammatory mechanism, activated by nonpathogenic bacteria, that selectively antagonizes transcription factor NF-kappaB. Bacteroides thetaiotaomicron targets transcriptionally active NF-kappaB subunit RelA, enhancing its nuclear export through a mechanism independent of nuclear export receptor Crm-1. Peroxisome proliferator activated receptor-gamma (PPAR-gamma), in complex with nuclear RelA, also undergoes nucleocytoplasmic redistribution in response to B. thetaiotaomicron. A decrease in PPAR-gamma abolishes both the nuclear export of RelA and the anti-inflammatory activity of B. thetaiotaomicron. This PPAR-gamma-dependent anti-inflammatory mechanism defines new cellular targets for therapeutic drug design and interventions for the treatment of chronic inflammation.
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              Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome.

              Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice-obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac from Taconic-plus three derivative lines generated by breeding these strains in a new, common environment. Analysis of metabolic parameters and gut microbiota in all strains and their environmentally normalized derivatives revealed strong interactions between microbiota, diet, breeding site, and metabolic phenotype. Strain-dependent and strain-independent correlations were found between specific microbiota and phenotypes, some of which could be transferred to germ-free recipient animals by fecal transplantation. Environmental reprogramming of microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus, development of obesity/metabolic syndrome is the result of interactions between gut microbiota, host genetics, and diet. In permissive genetic backgrounds, environmental reprograming of microbiota can ameliorate development of metabolic syndrome.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                27 May 2019
                2019
                : 10
                : 295
                Affiliations
                [1] 1School of Public Health, Xinjiang Medical University , Ürümqi, China
                [2] 2College of Basic Medical Science, Xinjiang Medical University , Ürümqi, China
                [3] 3Medical Department, The Fifth Affiliated Hospital of Xinjiang Medical University , Ürümqi, China
                [4] 4Health Management Institute, The First Affiliated Hospital of Xinjiang Medical University , Ürümqi, China
                Author notes

                Edited by: Anca Dana Dobrian, Eastern Virginia Medical School, United States

                Reviewed by: Venu Lagishetty, University of California, Los Angeles, United States; Wensheng Pan, Zhejiang Provincial People's Hospital, China

                *Correspondence: Patamu Mohemaiti patam0616@ 123456aliyun.com

                This article was submitted to Diabetes, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2019.00295
                6546033
                31191448
                068fd8ed-8f79-4692-8a57-656afdba3913
                Copyright © 2019 Nuli, Cai, Kadeer, Zhang and Mohemaiti.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 January 2019
                : 24 April 2019
                Page count
                Figures: 7, Tables: 7, Equations: 0, References: 48, Pages: 14, Words: 9232
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                gut microbiota,16s rrna,impaired glucose regulation,type 2 diabetes,uyghur,dietary survey

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