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      Compositional Alterations of Gut Microbiota in Patients with Diabetic Kidney Disease and Type 2 Diabetes Mellitus

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          Abstract

          Purpose

          Emerging evidence has revealed that gut microbiota plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T 2DM) and diabetic kidney disease (DKD). However, few studies have used metagenomic sequencing to analyze the alterations of gut microbiota community in patients with early-stage DKD.

          Methods

          We carried out metagenomic sequencing in fecal samples of 10 DKD patients (DKD group) and 10 T 2DM patients who appeared to be less prone to DKD (non-DKD group), aiming to compare the composition and function of gut microbiota between the DKD and non-DKD groups.

          Results

          The gut microbial community of the DKD group was significantly different from that of the non-DKD group, characterized by a marked increase in phylum Proteobacteria, genus Selenomonadales, Neosynechococcus, Shigella, Bilophila, Acidaminococcus, species, Escherichia coli, Bacteroides plebeius, Megasphaera elsdenii, Acidaminococcus unclassified, and Bilophila wadsworthia. The amounts of species Citrobacter farmeri and Syntrophaceticus schinkii were significantly and positively correlated with the urinary albumin creatinine ratio in the DKD group. Furthermore, functional analysis based on dbCAN and KEGG databases showed aberrant lipopolysaccharide (LPS) biosynthesis and carbohydrate metabolism in the gut microbiome of the DKD group.

          Conclusion

          Our findings provided evidence for alterations in the composition and function of gut microbiota in patients with DKD versus the non-DKD group. These data may contribute to a more comprehensive understanding of the pathological mechanisms of DKD.

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          Most cited references40

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          A human gut microbial gene catalogue established by metagenomic sequencing.

          To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.
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            Host-gut microbiota metabolic interactions.

            The composition and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiologically connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.
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              Proteobacteria: microbial signature of dysbiosis in gut microbiota.

              Recent advances in sequencing techniques, applied to the study of microbial communities, have provided compelling evidence that the mammalian intestinal tract harbors a complex microbial community whose composition is a critical determinant of host health in the context of metabolism and inflammation. Given that an imbalanced gut microbiota often arises from a sustained increase in abundance of the phylum Proteobacteria, the natural human gut flora normally contains only a minor proportion of this phylum. Here, we review studies that explored the association between an abnormal expansion of Proteobacteria and a compromised ability to maintain a balanced gut microbial community. We also propose that an increased prevalence of Proteobacteria is a potential diagnostic signature of dysbiosis and risk of disease.
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                Author and article information

                Journal
                Diabetes Metab Syndr Obes
                Diabetes Metab Syndr Obes
                dmso
                Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
                Dove
                1178-7007
                06 March 2022
                2022
                : 15
                : 755-765
                Affiliations
                [1 ]Dialysis Department of Nephrology Hospital, First Affiliated Hospital of Xi’an Jiaotong University , Xi’an, 710061, People’s Republic of China
                [2 ]Department of Nephrology, First Affiliated Hospital of Xi’an Jiaotong University , Xi’an, 710061, People’s Republic of China
                Author notes
                Correspondence: Zhigang Wang, First Affiliated Hospital of Xi’an Jiaotong University , West Yanta Road 277, Xi’an, 710061, People’s Republic of China, Email wangzhigang2017@xjtu.edu.cn
                Article
                347805
                10.2147/DMSO.S347805
                8911313
                35280499
                800f0f26-878a-4b4c-8b5e-8921deb9e227
                © 2022 He et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 04 November 2021
                : 25 February 2022
                Page count
                Figures: 6, Tables: 1, References: 43, Pages: 11
                Funding
                Funded by: the National Natural Science Foundation of China;
                This work was supported by the National Natural Science Foundation of China (No. 81700644).
                Categories
                Original Research

                Endocrinology & Diabetes
                diabetic kidney disease,gut microbiota,metagenomics,type 2 diabetes mellitus

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