The Role of Gut Microbiota and Microbiota-Related Serum Metabolites in the Progression of Diabetic Kidney Disease
Objective: Diabetic kidney disease (DKD) has become the major cause of end-stage renal disease (ESRD) associated with the progression of renal fibrosis. As gut microbiota dysbiosis is closely related to renal damage and fibrosis, we investigated the role of gut microbiota and microbiota-related seru...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:488b6a3f8dec454aaff7ed86e573cd1c2021-11-30T17:50:31ZThe Role of Gut Microbiota and Microbiota-Related Serum Metabolites in the Progression of Diabetic Kidney Disease1663-981210.3389/fphar.2021.757508https://doaj.org/article/488b6a3f8dec454aaff7ed86e573cd1c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.757508/fullhttps://doaj.org/toc/1663-9812Objective: Diabetic kidney disease (DKD) has become the major cause of end-stage renal disease (ESRD) associated with the progression of renal fibrosis. As gut microbiota dysbiosis is closely related to renal damage and fibrosis, we investigated the role of gut microbiota and microbiota-related serum metabolites in DKD progression in this study.Methods: Fecal and serum samples obtained from predialysis DKD patients from January 2017 to December 2019 were detected using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Forty-one predialysis patients were divided into two groups according to their estimated glomerular filtration rate (eGFR): the DKD non-ESRD group (eGFR ≥ 15 ml/min/1.73 m2) (n = 22), and the DKD ESRD group (eGFR < 15 ml/min/1.73 m2) (n = 19). The metabolic pathways related to differential serum metabolites were obtained by the KEGG pathway analysis. Differences between the two groups relative to gut microbiota profiles and serum metabolites were investigated, and associations between gut microbiota and metabolite concentrations were assessed. Correlations between clinical indicators and both microbiota-related metabolites and gut microbiota were calculated by Spearman rank correlation coefficient and visualized by heatmap.Results: Eleven different intestinal floras and 239 different serum metabolites were identified between the two groups. Of 239 serum metabolites, 192 related to the 11 different intestinal flora were mainly enriched in six metabolic pathways, among which, phenylalanine and tryptophan metabolic pathways were most associated with DKD progression. Four microbiota-related metabolites in the phenylalanine metabolic pathway [hippuric acid (HA), L-(−)-3-phenylactic acid, trans-3-hydroxy-cinnamate, and dihydro-3-coumaric acid] and indole-3 acetic acid (IAA) in the tryptophan metabolic pathway positively correlated with DKD progression, whereas L-tryptophan in the tryptophan metabolic pathway had a negative correlation. Intestinal flora g_Abiotrophia and g_norank_f_Peptococcaceae were positively correlated with the increase in renal function indicators and serum metabolite HA. G_Lachnospiraceae_NC2004_Group was negatively correlated with the increase in renal function indicators and serum metabolites [L-(−)-3-phenyllactic acid and IAA].Conclusions: This study highlights the interaction among gut microbiota, serum metabolites, and clinical indicators in predialysis DKD patients, and provides new insights into the role of gut microbiota and microbiota-related serum metabolites that were enriched in the phenylalanine and tryptophan metabolic pathways, which correlated with the progression of DKD.Qing ZhangQing ZhangYanmei ZhangYanmei ZhangLu ZengLu ZengGuowei ChenLa ZhangMeifang LiuMeifang LiuHongqin ShengHongqin ShengXiaoxuan HuJingxu SuDuo ZhangDuo ZhangFuhua LuFuhua LuXusheng LiuXusheng LiuLei ZhangLei ZhangFrontiers Media S.A.articlediabetic kidney diseasegut microbiotaserum metabolitesphenylalanine metabolic pathwaytryptophan metabolic pathwayG_AbiotrophiaTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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DOAJ |
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EN |
| topic |
diabetic kidney disease gut microbiota serum metabolites phenylalanine metabolic pathway tryptophan metabolic pathway G_Abiotrophia Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
diabetic kidney disease gut microbiota serum metabolites phenylalanine metabolic pathway tryptophan metabolic pathway G_Abiotrophia Therapeutics. Pharmacology RM1-950 Qing Zhang Qing Zhang Yanmei Zhang Yanmei Zhang Lu Zeng Lu Zeng Guowei Chen La Zhang Meifang Liu Meifang Liu Hongqin Sheng Hongqin Sheng Xiaoxuan Hu Jingxu Su Duo Zhang Duo Zhang Fuhua Lu Fuhua Lu Xusheng Liu Xusheng Liu Lei Zhang Lei Zhang The Role of Gut Microbiota and Microbiota-Related Serum Metabolites in the Progression of Diabetic Kidney Disease |
| description |
Objective: Diabetic kidney disease (DKD) has become the major cause of end-stage renal disease (ESRD) associated with the progression of renal fibrosis. As gut microbiota dysbiosis is closely related to renal damage and fibrosis, we investigated the role of gut microbiota and microbiota-related serum metabolites in DKD progression in this study.Methods: Fecal and serum samples obtained from predialysis DKD patients from January 2017 to December 2019 were detected using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Forty-one predialysis patients were divided into two groups according to their estimated glomerular filtration rate (eGFR): the DKD non-ESRD group (eGFR ≥ 15 ml/min/1.73 m2) (n = 22), and the DKD ESRD group (eGFR < 15 ml/min/1.73 m2) (n = 19). The metabolic pathways related to differential serum metabolites were obtained by the KEGG pathway analysis. Differences between the two groups relative to gut microbiota profiles and serum metabolites were investigated, and associations between gut microbiota and metabolite concentrations were assessed. Correlations between clinical indicators and both microbiota-related metabolites and gut microbiota were calculated by Spearman rank correlation coefficient and visualized by heatmap.Results: Eleven different intestinal floras and 239 different serum metabolites were identified between the two groups. Of 239 serum metabolites, 192 related to the 11 different intestinal flora were mainly enriched in six metabolic pathways, among which, phenylalanine and tryptophan metabolic pathways were most associated with DKD progression. Four microbiota-related metabolites in the phenylalanine metabolic pathway [hippuric acid (HA), L-(−)-3-phenylactic acid, trans-3-hydroxy-cinnamate, and dihydro-3-coumaric acid] and indole-3 acetic acid (IAA) in the tryptophan metabolic pathway positively correlated with DKD progression, whereas L-tryptophan in the tryptophan metabolic pathway had a negative correlation. Intestinal flora g_Abiotrophia and g_norank_f_Peptococcaceae were positively correlated with the increase in renal function indicators and serum metabolite HA. G_Lachnospiraceae_NC2004_Group was negatively correlated with the increase in renal function indicators and serum metabolites [L-(−)-3-phenyllactic acid and IAA].Conclusions: This study highlights the interaction among gut microbiota, serum metabolites, and clinical indicators in predialysis DKD patients, and provides new insights into the role of gut microbiota and microbiota-related serum metabolites that were enriched in the phenylalanine and tryptophan metabolic pathways, which correlated with the progression of DKD. |
| format |
article |
| author |
Qing Zhang Qing Zhang Yanmei Zhang Yanmei Zhang Lu Zeng Lu Zeng Guowei Chen La Zhang Meifang Liu Meifang Liu Hongqin Sheng Hongqin Sheng Xiaoxuan Hu Jingxu Su Duo Zhang Duo Zhang Fuhua Lu Fuhua Lu Xusheng Liu Xusheng Liu Lei Zhang Lei Zhang |
| author_facet |
Qing Zhang Qing Zhang Yanmei Zhang Yanmei Zhang Lu Zeng Lu Zeng Guowei Chen La Zhang Meifang Liu Meifang Liu Hongqin Sheng Hongqin Sheng Xiaoxuan Hu Jingxu Su Duo Zhang Duo Zhang Fuhua Lu Fuhua Lu Xusheng Liu Xusheng Liu Lei Zhang Lei Zhang |
| author_sort |
Qing Zhang |
| title |
The Role of Gut Microbiota and Microbiota-Related Serum Metabolites in the Progression of Diabetic Kidney Disease |
| title_short |
The Role of Gut Microbiota and Microbiota-Related Serum Metabolites in the Progression of Diabetic Kidney Disease |
| title_full |
The Role of Gut Microbiota and Microbiota-Related Serum Metabolites in the Progression of Diabetic Kidney Disease |
| title_fullStr |
The Role of Gut Microbiota and Microbiota-Related Serum Metabolites in the Progression of Diabetic Kidney Disease |
| title_full_unstemmed |
The Role of Gut Microbiota and Microbiota-Related Serum Metabolites in the Progression of Diabetic Kidney Disease |
| title_sort |
role of gut microbiota and microbiota-related serum metabolites in the progression of diabetic kidney disease |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/488b6a3f8dec454aaff7ed86e573cd1c |
| work_keys_str_mv |
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