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      Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review

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          Abstract

          Diabetic kidney disease (DKD) is one of the main microvascular complications of diabetes mellitus, as well as the leading cause of end-stage renal disease. Intestinal microbiota has emerged as a crucial regulator of its occurrence and development. Dysbiosis of the intestinal microbiota can disrupt the intestinal mucosal barrier, abnormal immunological response, reduction in short-chain fatty acid metabolites, and elevation of uremic toxins, all closely related to the occurrence and development of DKD. However, the underlying mechanisms of how intestinal microbiota and its metabolites influence the onset and progression of DKD has not been fully elucidated. In the current review, we will try to summarize the microecological mechanism of DKD by focusing on three aspects: the intestinal microbiota and its associated metabolites, and the “gut–kidney axis,” and try to summarize therapies targeted at managing the intestinal microbiota, expecting to provide theoretical basis for the subsequent study of the relationship between intestinal homeostasis and DKD, and will open an emerging perspective and orientation for DKD treatment.

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          Gut metagenome in European women with normal, impaired and diabetic glucose control.

          Type 2 diabetes (T2D) is a result of complex gene-environment interactions, and several risk factors have been identified, including age, family history, diet, sedentary lifestyle and obesity. Statistical models that combine known risk factors for T2D can partly identify individuals at high risk of developing the disease. However, these studies have so far indicated that human genetics contributes little to the models, whereas socio-demographic and environmental factors have greater influence. Recent evidence suggests the importance of the gut microbiota as an environmental factor, and an altered gut microbiota has been linked to metabolic diseases including obesity, diabetes and cardiovascular disease. Here we use shotgun sequencing to characterize the faecal metagenome of 145 European women with normal, impaired or diabetic glucose control. We observe compositional and functional alterations in the metagenomes of women with T2D, and develop a mathematical model based on metagenomic profiles that identified T2D with high accuracy. We applied this model to women with impaired glucose tolerance, and show that it can identify women who have a diabetes-like metabolism. Furthermore, glucose control and medication were unlikely to have major confounding effects. We also applied our model to a recently described Chinese cohort and show that the discriminant metagenomic markers for T2D differ between the European and Chinese cohorts. Therefore, metagenomic predictive tools for T2D should be specific for the age and geographical location of the populations studied.
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            Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22.

            Endogenous tryptophan (Trp) metabolites have an important role in mammalian gut immune homeostasis, yet the potential contribution of Trp metabolites from resident microbiota has never been addressed experimentally. Here, we describe a metabolic pathway whereby Trp metabolites from the microbiota balance mucosal reactivity in mice. Switching from sugar to Trp as an energy source (e.g., under conditions of unrestricted Trp availability), highly adaptive lactobacilli are expanded and produce an aryl hydrocarbon receptor (AhR) ligand-indole-3-aldehyde-that contributes to AhR-dependent Il22 transcription. The resulting IL-22-dependent balanced mucosal response allows for survival of mixed microbial communities yet provides colonization resistance to the fungus Candida albicans and mucosal protection from inflammation. Thus, the microbiota-AhR axis might represent an important strategy pursued by coevolutive commensalism for fine tuning host mucosal reactivity contingent on Trp catabolism. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Role of gut microbiota in type 2 diabetes pathophysiology

              A substantial body of literature has provided evidence for the role of gut microbiota in metabolic diseases including type 2 diabetes. However, reports vary regarding the association of particular taxonomic groups with disease. In this systematic review, we focused on the potential role of different bacterial taxa affecting diabetes. We have summarized evidence from 42 human studies reporting microbial associations with disease, and have identified supporting preclinical studies or clinical trials using treatments with probiotics. Among the commonly reported findings, the genera of Bifidobacterium, Bacteroides, Faecalibacterium, Akkermansia and Roseburia were negatively associated with T2D, while the genera of Ruminococcus, Fusobacterium, and Blautia were positively associated with T2D. We also discussed potential molecular mechanisms of microbiota effects in the onset and progression of T2D.
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                Author and article information

                Contributors
                Journal
                Open Life Sci
                Open Life Sci
                biol
                Open Life Sciences
                De Gruyter
                2391-5412
                06 August 2024
                2024
                : 19
                : 1
                : 20220909
                Affiliations
                Clinical College of Chinese Medicine, Hubei University of Chinese Medicine , Wuhan 430061, China
                The First Clinical Medical School, Hubei University of Chinese Medicine , Wuhan, 430061, China
                Department of Nephrology, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine , Wuhan, 430061, China
                Hubei Key Laboratory of Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine , Wuhan, 430061, China
                Article
                biol-2022-0909
                10.1515/biol-2022-0909
                11306963
                39119482
                d3e01dd6-7327-4e57-968a-2771030e5d69
                © 2024 the author(s), published by De Gruyter

                This work is licensed under the Creative Commons Attribution 4.0 International License.

                History
                : 15 April 2024
                : 27 May 2024
                : 17 June 2024
                Page count
                Pages: 11
                Categories
                Review Article

                diabetic kidney disease,intestinal microbiota,metabolite,“gut–kidney axis”

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