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      Huang-Lian-Jie-Du-Decoction Ameliorates Hyperglycemia and Insulin Resistant in Association With Gut Microbiota Modulation

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          Abstract

          Background: Huang-Lian-Jie-Du-Decoction (HLJDD), a prescription of traditional Chinese medicine, has been clinically used to treat diabetes for thousands of years and its mechanism was reported to be related to gut microbiota. However, no study has explored the effect of HLJDD on the gut microbiota in type 2 diabetes mellitus (T2DM) yet. Therefore, in this study, we investigated the modulation of gut microbiota induced by HLJDD treatment in T2DM in order to unveil the underlying mechanism.

          Methods: A combination of high-fat diet (HFD) and streptozotocin (STZ) was used to induce T2DM in rats. Bacterial communities in the fecal samples from the control group, the T2DM model group, and the HLJDD-treated T2DM group were analyzed by 16S gene sequencing, followed with a subset sample analyzed by shotgun sequencing.

          Results: The HLJDD treatment significantly ameliorated hyperglycemia and inflammation in T2DM rats. Additionally, our results indicated that HLJDD treatment could not only restore the gut dysbiosis in T2DM rats, which was proved by an increasing amount of short chain fatty acids (SCFAs)-producing and anti-inflammatory bacteria such as Parabacteroides, Blautia, and Akkermansia as well as a decreasing amount of conditioned pathogenic bacteria (e.g., Aerococcus, Staphylococcus, and Corynebacterium), but also modulate the dysregulated function of gut microbiome in T2DM rats, including an up-regulation in bile acid biosynthesis as well as a reduction in glycolysis/gluconeogenesis and nucleotide metabolism.

          Conclusion: HLJDD treatment could ameliorate hyperglycemia and restore the dysregulated microbiota structure and function to a normal condition mainly by increasing SCFAs-producing bacteria and reducing conditioned pathogenic bacteria in T2DM rats, which provides insights into the mechanism of HLJDD treatment for T2DM from the view of gut microbiota.

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          Most cited references37

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          FLASH: fast length adjustment of short reads to improve genome assemblies.

          Next-generation sequencing technologies generate very large numbers of short reads. Even with very deep genome coverage, short read lengths cause problems in de novo assemblies. The use of paired-end libraries with a fragment size shorter than twice the read length provides an opportunity to generate much longer reads by overlapping and merging read pairs before assembling a genome. We present FLASH, a fast computational tool to extend the length of short reads by overlapping paired-end reads from fragment libraries that are sufficiently short. We tested the correctness of the tool on one million simulated read pairs, and we then applied it as a pre-processor for genome assemblies of Illumina reads from the bacterium Staphylococcus aureus and human chromosome 14. FLASH correctly extended and merged reads >99% of the time on simulated reads with an error rate of <1%. With adequately set parameters, FLASH correctly merged reads over 90% of the time even when the reads contained up to 5% errors. When FLASH was used to extend reads prior to assembly, the resulting assemblies had substantially greater N50 lengths for both contigs and scaffolds. The FLASH system is implemented in C and is freely available as open-source code at http://www.cbcb.umd.edu/software/flash. t.magoc@gmail.com.
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            Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice

            Recent evidence indicates that the gut microbiota plays a key role in the pathophysiology of obesity. Indeed, diet-induced obesity (DIO) has been associated to substantial changes in gut microbiota composition in rodent models. In the context of obesity, enhanced adiposity is accompanied by low-grade inflammation of this tissue but the exact link with gut microbial community remains unknown. In this report, we studied the consequences of high-fat diet (HFD) administration on metabolic parameters and gut microbiota composition over different periods of time. We found that Akkermansia muciniphila abundance was strongly and negatively affected by age and HFD feeding and to a lower extend Bilophila wadsworthia was the only taxa following an opposite trend. Different approaches, including multifactorial analysis, showed that these changes in Akkermansia muciniphila were robustly correlated with the expression of lipid metabolism and inflammation markers in adipose tissue, as well as several circulating parameters (i.e., glucose, insulin, triglycerides, leptin) from DIO mice. Thus, our data shows the existence of a link between gut Akkermansia muciniphila abundance and adipose tissue homeostasis on the onset of obesity, thus reinforcing the beneficial role of this bacterium on metabolism.
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              Analysis of the chronic wound microbiota of 2,963 patients by 16S rDNA pyrosequencing.

              The extent to which microorganisms impair wound healing is an ongoing controversy in the management of chronic wounds. Because the high diversity and extreme variability of the microbiota between individual chronic wounds lead to inconsistent findings in small cohort studies, evaluation of a large number of chronic wounds using identical sequencing and bioinformatics methods is necessary for clinicians to be able to select appropriate empiric therapies. In this study, we utilized 16S rDNA pyrosequencing to analyze the composition of the bacterial communities present in samples obtained from patients with chronic diabetic foot ulcers (N = 910), venous leg ulcers (N = 916), decubitus ulcers (N = 767), and nonhealing surgical wounds (N = 370). The wound samples contained a high proportion of Staphylococcus and Pseudomonas species in 63 and 25% of all wounds, respectively; however, a high prevalence of anaerobic bacteria and bacteria traditionally considered commensalistic was also observed. Our results suggest that neither patient demographics nor wound type influenced the bacterial composition of the chronic wound microbiome. Collectively, these findings indicate that empiric antibiotic selection need not be based on nor altered for wound type. Furthermore, the results provide a much clearer understanding of chronic wound microbiota in general; clinical application of this new knowledge over time may help in its translation to improved wound healing outcomes.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                08 October 2018
                2018
                : 9
                : 2380
                Affiliations
                [1] 1School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, China
                [2] 2School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine , Guangzhou, China
                [3] 3School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University , Guangzhou, China
                Author notes

                Edited by: George Tsiamis, University of Patras, Greece

                Reviewed by: E-Hu Liu, China Pharmaceutical University, China; Yi Dai, Jinan University, China

                *Correspondence: Qiongfeng Liao, liaoqf2075@ 123456yahoo.com Zhiyong Xie, xiezy2074@ 123456yahoo.com

                This article was submitted to Systems Microbiology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2018.02380
                6186778
                30349514
                3ede4f16-8a34-4275-a8b9-07eda844f5f9
                Copyright © 2018 Chen, Liao, Lu, Wang, Lin, Zhang, Li, Liu, Liao and Xie.

                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
                : 23 May 2018
                : 18 September 2018
                Page count
                Figures: 9, Tables: 2, Equations: 0, References: 65, Pages: 16, Words: 0
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81473319
                Award ID: 81473540
                Funded by: Natural Science Foundation of Guangdong Province 10.13039/501100003453
                Award ID: 2017A030311022
                Award ID: 2015A030313123
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                16s gene sequencing,gut microbiota,hljdd,metagenomics,type 2 diabetes mellitus

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