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      Discrepant gut microbiota markers for the classification of obesity-related metabolic abnormalities

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          Abstract

          The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for obesity in patients with different metabolic abnormalities and investigate their relationships with clinical indicators, 1,914 Chinese adults were enrolled for 16S rRNA gene sequencing in this retrospective study. Based on GM composition, Random forest classifiers were constructed to screen the obesity patients with (Group OA) or without metabolic diseases (Group O) from healthy individuals (Group H), and high accuracies were observed for the discrimination of Group O and Group OA (areas under the receiver operating curve (AUC) equal to 0.68 and 0.76, respectively). Furthermore, six GM markers were shared by obesity patients with various metabolic disorders ( Bacteroides, Parabacteroides, Blautia, Alistipes, Romboutsia and Roseburia). As for the discrimination with Group O, Group OA exhibited low accuracy (AUC = 0.57). Nonetheless, GM classifications to distinguish between Group O and the obese patients with specific metabolic abnormalities were not accurate (AUC values from 0.59 to 0.66). Common biomarkers were identified for the obesity patients with high uric acid, high serum lipids and high blood pressure, such as Clostridium XIVa, Bacteroides and Roseburia. A total of 20 genera were associated with multiple significant clinical indicators. For example, Blautia, Romboutsia, Ruminococcus2, Clostridium sensu stricto and Dorea were positively correlated with indicators of bodyweight (including waistline and body mass index) and serum lipids (including low density lipoprotein, triglyceride and total cholesterol). In contrast, the aforementioned clinical indicators were negatively associated with Bacteroides, Roseburia, Butyricicoccus, Alistipes, Parasutterella, Parabacteroides and Clostridium IV. Generally, these biomarkers hold the potential to predict obesity-related metabolic abnormalities, and interventions based on these biomarkers might be beneficial to weight loss and metabolic risk improvement.

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          Most cited references14

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          Enterotypes in the landscape of gut microbial community composition

          Population stratification is a useful approach towards a better understanding of complex biological problems in human health and well-being. The proposal that such stratification applies to the human gut microbiome, in the form of distinct community composition types, termed “enterotypes”, was met with both excitement and controversy. In view of accumulated data and re-analyses since the original work, we revisit the enterotype concept, discuss different methods of dividing up the landscape of possible microbiome configurations, and put these concepts into a functional, ecological and medical context. As enterotypes are of use in describing the gut microbial community landscape and may become relevant in clinical practice, we aim to reconcile differing views and encourage a balanced application of the concept.
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            Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity

            This population-based study calculates lifetime risk estimates for incident cardiovascular disease and subtypes of cardiovascular disease and estimates years lived with and without cardiovascular disease by weight status. Question What is the association of body mass index with cardiovascular disease (CVD) morbidity and mortality? Findings In this population-based study, overweight and obesity were associated with significantly increased risk for CVD. Obesity was associated with shorter longevity and a greater proportion of life lived with CVD; overweight was associated with similar longevity as normal weight but at the expense of a greater proportion of life lived with CVD. Meaning These results provide critical perspective on CVD associated with overweight and obesity and challenge both the obesity paradox as well as the view that overweight is associated with greater longevity. Importance Prior studies have demonstrated lower all-cause mortality in individuals who are overweight compared with those with normal body mass index (BMI), but whether this may come at the cost of greater burden of cardiovascular disease (CVD) is unknown. Objective To calculate lifetime risk estimates of incident CVD and subtypes of CVD and to estimate years lived with and without CVD by weight status. Design, Setting, and Participants In this population-based study, we used pooled individual-level data from adults (baseline age, 20-39, 40-59, and 60-79 years) across 10 large US prospective cohorts, with 3.2 million person-years of follow-up from 1964 to 2015. All participants were free of clinical CVD at baseline with available BMI index and CVD outcomes data. Data were analyzed from October 2016 to July 2017. Exposures World Health Organization–standardized BMI categories. Main Outcomes and Measures Total CVD and CVD subtype, including fatal and nonfatal coronary heart disease, stroke, congestive heart failure, and other CVD deaths. Heights and weights were measured directly by investigators in each study, and BMI was calculated as weight in kilograms divided by height in meters squared. We performed (1) modified Kaplan-Meier analysis to estimate lifetime risks, (2) adjusted competing Cox models to estimate joint cumulative risks for CVD or noncardiovascular death, and (3) the Irwin restricted mean to estimate years lived free of and with CVD. Results Of the 190 672 in-person examinations included in this study, the mean (SD) age was 46.0 (15.0) years for men and 58.7 (12.9) years for women, and 140 835 patients (73.9%) were female. Compared with individuals with a normal BMI (defined as a BMI of 18.5 to 24.9), lifetime risks for incident CVD were higher in middle-aged adults in the overweight and obese groups. Compared with normal weight, among middle-aged men and women, competing hazard ratios for incident CVD were 1.21 (95% CI, 1.14-1.28) and 1.32 (95% CI, 1.24-1.40), respectively, for overweight (BMI, 25.0-29.9), 1.67 (95% CI, 1.55-1.79) and 1.85 (95% CI, 1.72-1.99) for obesity (BMI, 30.0-39.9), and 3.14 (95% CI, 2.48-3.97) and 2.53 (95% CI, 2.20-2.91) for morbid obesity (BMI, ≥40.0). Higher BMI had the strongest association with incident heart failure among CVD subtypes. Average years lived with CVD were longer for middle-aged adults in the overweight and obese groups compared with adults in the normal BMI group. Similar patterns were observed in younger and older adults. Conclusions and Relevance In this study, obesity was associated with shorter longevity and significantly increased risk of cardiovascular morbidity and mortality compared with normal BMI. Despite similar longevity compared with normal BMI, overweight was associated with significantly increased risk of developing CVD at an earlier age, resulting in a greater proportion of life lived with CVD morbidity.
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              The pathophysiology of hypertension in patients with obesity.

              The combination of obesity and hypertension is associated with high morbidity and mortality because it leads to cardiovascular and kidney disease. Potential mechanisms linking obesity to hypertension include dietary factors, metabolic, endothelial and vascular dysfunction, neuroendocrine imbalances, sodium retention, glomerular hyperfiltration, proteinuria, and maladaptive immune and inflammatory responses. Visceral adipose tissue also becomes resistant to insulin and leptin and is the site of altered secretion of molecules and hormones such as adiponectin, leptin, resistin, TNF and IL-6, which exacerbate obesity-associated cardiovascular disease. Accumulating evidence also suggests that the gut microbiome is important for modulating these mechanisms. Uric acid and altered incretin or dipeptidyl peptidase 4 activity further contribute to the development of hypertension in obesity. The pathophysiology of obesity-related hypertension is especially relevant to premenopausal women with obesity and type 2 diabetes mellitus who are at high risk of developing arterial stiffness and endothelial dysfunction. In this Review we discuss the relationship between obesity and hypertension with special emphasis on potential mechanisms and therapeutic targeting that might be used in a clinical setting.
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                Author and article information

                Contributors
                k.zhou@hust.edu.cn
                shuaicli@cityu.edu.hk
                wenkuidai2-c@my.cityu.edu.hk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                17 September 2019
                17 September 2019
                2019
                : 9
                : 13424
                Affiliations
                [1 ]ISNI 0000 0004 1761 8894, GRID grid.414252.4, Health management institute, , People’s Liberation Army General Hospital, ; Beijing, China
                [2 ]ISNI 0000 0004 0368 7223, GRID grid.33199.31, Wuhan National Laboratory for Optoelectronics, , Huazhong University of Science and Technology, ; Wuhan, Hubei Province China
                [3 ]Department of Microbial Research, WeHealthGene Institute, Shenzhen, Guangdong Province China
                [4 ]ISNI 0000 0004 1806 5224, GRID grid.452787.b, Joint Laboratory of Micro-ecology and Children’s Health, , Shenzhen Children’s Hospital & Shenzhen WeHealthGene Co. Ltd., ; Shenzhen, Guangdong Province China
                [5 ]National Research Institute for Health, Beijing, China
                [6 ]ISNI 0000 0004 1792 6846, GRID grid.35030.35, Department of Computer Science, College of Science and Engineering, , City University of Hong Kong, ; Hong Kong, China
                [7 ]ISNI 0000 0000 9878 7032, GRID grid.216938.7, School of Statistics and Data Science, , Nankai University, ; Tianjin, China
                [8 ]ISNI 0000 0004 1760 6682, GRID grid.410570.7, Southwest Hospital of Third Military Medical University, ; Chongqing, China
                [9 ]Health management center, The 910th Hospital of People’s Liberation Army, Quanzhou, Fujian Province China
                [10 ]ISNI 0000 0004 1771 3349, GRID grid.415954.8, The China-Japan Union Hospital of Jilin University, ; Changchun, Jilin Province China
                [11 ]ISNI 0000 0004 1806 5224, GRID grid.452787.b, Department of Respiratory, , Shenzhen Children’s Hospital, ; Shenzhen, Guangdong Province China
                [12 ]Department of Cardiology, Longkou People’s Hospital, Longkou, Shandong Province China
                [13 ]ISNI 0000 0004 1936 8200, GRID grid.55602.34, Department of Mathematics and Statistics, , Dalhousie University, ; Halifax, Nova Scotia Canada
                [14 ]GRID grid.414011.1, Department of Health Management, , Henan Provincial People’s Hospital, ; Zhengzhou, Henan Province China
                Article
                49462
                10.1038/s41598-019-49462-w
                6748942
                31530820
                03bc227f-90ae-4d69-9402-caed15dcd0ff
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 4 December 2018
                : 20 August 2019
                Funding
                Funded by: The State Science and Technology Support Program (No.2012BAI37B04) The Military Healthcare Program (No.15BJZ48 and No.16BJZ40)
                Funded by: FundRef https://doi.org/10.13039/501100010877, Shenzhen Science and Technology Innovation Commission;
                Award ID: JCYJ20170816170527583
                Award Recipient :
                Categories
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                © The Author(s) 2019

                Uncategorized
                data mining,microbial ecology
                Uncategorized
                data mining, microbial ecology

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