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      Association Between Serum Thyroid-Stimulating Hormone Levels and Salivary Microbiome Shifts

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          Abstract

          High serum thyroid-stimulating hormone (TSH) levels are linked to many metabolic disorders, but the effects of TSH levels on the oral microbiota are still largely unknown. This study aimed to explore the association between the salivary microbiome in adults and serum TSH levels. Saliva and fasting blood samples were obtained from a health census conducted in Southeast China. All participants were divided according to serum TSH levels. The microbial genetic profiles and changes were acquired by 16S rDNA sequencing and bioinformatics analysis. Relevant anthropometric and biochemical measurements such as insulin resistance, blood lipids, and body composition were evaluated with laboratory tests and physical examinations. The salivary microbiome in individuals with higher TSH level showed significantly higher taxa diversity. Principal coordinates analysis and partial least squares discriminant analysis showed distinct clustering in the Abnormal and Normal Groups (Adonis, P=0.0320). Granulicatella was identified as a discriminative genus for comparison of the two groups. Fasting serum insulin, Homeostatic Model Assessment for Insulin Resistance, and hemoglobin A1 were elevated in the Abnormal Group ( P<0.05), showing the presence of insulin resistance in individuals with abnormal higher serum TSH levels. Distance-based redundancy analysis revealed the association of this distinctive difference with salivary microbiome. In conclusion, shifts in microbial profile were observed in the saliva of individuals with different serum TSH levels, and insulin resistance may play an important role in the biochemical and microbial alteration.

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          Most cited references77

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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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            Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes

            The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM.
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              Thyroid hormone regulation of metabolism.

              Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5'-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                26 February 2021
                2021
                : 11
                : 603291
                Affiliations
                [1] 1 Department of Endodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University, School of Medicine , Shanghai, China
                [2] 2 National Clinical Research Center for Oral Diseases , Shanghai, China
                [3] 3 Shanghai Key Laboratory of Stomatology , Shanghai, China
                [4] 4 Shanghai Research Institute of Stomatology , Shanghai, China
                [5] 5 Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China
                Author notes

                Edited by: You Zhou, Cardiff University, United Kingdom

                Reviewed by: Yan Li, Cleveland Clinic, United States; Selvasankar Murugesan, Sidra Medicine, Qatar

                *Correspondence: Zhengwei Huang, huangzhengwei@ 123456shsmu.edu.cn ; Yingli Lu, luyingli2008@ 123456126.com

                †These authors share first authorship

                This article was submitted to Microbiome in Health and Disease, a section of the journal Frontiers in Cellular and Infection Microbiology

                Article
                10.3389/fcimb.2021.603291
                7952758
                33718264
                ecd691a7-4c69-4fa1-9074-4ab6e8843b5d
                Copyright © 2021 Dong, Zhao, Yuan, Zhu, Wang, Xia, Lu and Huang

                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
                : 12 September 2020
                : 11 January 2021
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 77, Pages: 12, Words: 4871
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81570964, 81371143
                Categories
                Cellular and Infection Microbiology
                Original Research

                Infectious disease & Microbiology
                thyroid stimulating hormone,salivary microbiome,16s rdna sequencing,insulin resistance,community shift

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