Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy

Zhang, Lili; Wang, Zhisheng; Zhang, Xiaona; Zhao, Lu; Chu, Jinjin; Li, Haibo; Sun, Wenchang; Yang, Chunjuan; Wang, Hui; Dai, Wenqing; Yan, Shushan; Chen, Xiaohua; Xu, Dongmei

doi:10.1128/spectrum.00324-22

Cited by 40 publications

(37 citation statements)

References 60 publications

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“…Faecalibacterium was proven to increase the intestinal synthesis of glucagon-like peptide-1, peptide YY, acetate and butyrate help to maintain glucose homeostasis ( 58 ). In this study, Faecalibacterium was depleted in DC, corroborating previous reports that linked Faecalibacterium to positive metabolic outcomes ( 29 , 33 , 59 – 61 ). These findings revealed that the alternation of gut microbiota at the genus level was closely related to DC, and the increase of Bifidobacterium , Lactobacillus and Faecalibacterium might be responsible for the pathology of DC.…”

Section: Discussionsupporting

confidence: 92%

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Specific alterations of gut microbiota in diabetic microvascular complications: A systematic review and meta-analysis

Fu²,

Liu³

et al. 2022

Front. Endocrinol.

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BackgroundThe role of gut microbiota in diabetes mellitus (DM) and its complications has been widely accepted. However, the alternation of gut microbiota in diabetic microvascular complications (DC) remains to be determined.MethodsPublications (till August 20th, 2022) on gut microbiota in patients with DC were retrieved from PubMed, Web of Science, Embase and Cochrane. Review Manager 5.3 was performed to estimate the standardized mean difference (SMD) and 95% confidence interval (CI) and calculate alpha diversity indices and the relative abundance of gut microbiota between patients in DC v.s. DM and DC v.s. healthy controls (HC).ResultsWe included 13 studies assessing 329 patients with DC, 232 DM patients without DC, and 241 HC. Compared to DM, patients with DC shared a significantly lower Simpson index (SMD = -0.59, 95% CI [-0.82, -0.36], p < 0.00001), but a higher ACE index (SMD = 0.42, 95% CI[0.11, 0.74], p = 0.009). Compared to HC, DC patients held a lower ACE index (SMD = -0.61, 95% CI[-1.20, -0.02], p = 0.04). The relative abundances of phylum Proteobacteria (SMD = 0.03, 95% CI[0.01, 0.04], p = 0.003, v.s. HC) and genus Klebsiella (SMD = 0.00, 95% CI[0.00, 0.00], p < 0.00001, v.s. HC) were enriched, accompanying with depleted abundances of phylum Firmicutes (SMD = -0.06, 95% CI[-0.11, -0.01], p = 0.02, v.s. HC), genera Bifidobacterium (SMD = -0.01, 95% CI[-0.02,-0.01], p < 0.0001, v.s. DM), Faecalibacterium (SMD = -0.01, 95% CI[-0.02, -0.00], p = 0.009, v.s. DM; SMD = -0.02, 95% CI[-0.02, -0.01], p < 0.00001, v.s. HC) and Lactobacillus (SMD = 0.00, 95% CI[-0.00, -0.00], p < 0.00001, v.s. HC) in DC.ConclusionsGut microbiota perturbations with the depletion of alpha diversity and certain short-chain fatty acids (SCFAs)-producing bacteria were associated with the pathology of DC. Therefore, gut microbiota might serve as a promising approach for the diagnosis and treatment of DC. Further investigations are required to study the mechanisms by which gut dysbiosis acts on the onset and progression of DC.

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Section: Discussionsupporting

confidence: 92%

“…The total 13 studies ( 15 – 17 , 24 – 33 ) captured 329 patients with DC, 232 DM patients without DC, and 241 HC, with the territorial scope covering India (2/13), USA (2/13) and China (9/13). Seven (7/13) of the studies focused on DKD, five (5/13) focused on DR, and one (1/13) focused on DPN.…”

Section: Resultsmentioning

confidence: 99%

Specific alterations of gut microbiota in diabetic microvascular complications: A systematic review and meta-analysis

Fu²,

Liu³

et al. 2022

Front. Endocrinol.

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“…DKD patients displayed dysbiosis with composition, richness and diversity in gut microbiota (17)(18)(19). Roseburia intestinalis was significantly decreased while Bacteroides stercoris was increased in DKD patients (20). Furthermore, studies in early DKD caused by type 1 diabetes indicated that differences in gut microbiota and serum metabolite profiles were dependent on albuminuria levels (21).…”

Section: Gut Microbiota and Its Metabolites Gut Microbiotamentioning

confidence: 99%

Gut microbiota and its metabolites – molecular mechanisms and management strategies in diabetic kidney disease

Mao

Gao²,

Li³

et al. 2023

Front. Immunol.

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Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes mellitus and is also one of the serious risk factors in cardiovascular events, end-stage renal disease, and mortality. DKD is associated with the diversified, compositional, and functional alterations of gut microbiota. The interaction between gut microbiota and host is mainly achieved through metabolites, which are small molecules produced by microbial metabolism from exogenous dietary substrates and endogenous host compounds. The gut microbiota plays a critical role in the pathogenesis of DKD by producing multitudinous metabolites. Nevertheless, detailed mechanisms of gut microbiota and its metabolites involved in the occurrence and development of DKD have not been completely elucidated. This review summarizes the specific classes of gut microbiota-derived metabolites, aims to explore the molecular mechanisms of gut microbiota in DKD pathophysiology and progression, recognizes biomarkers for the screening, diagnosis, and prognosis of DKD, as well as provides novel therapeutic strategies for DKD.

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“…To date, considerable studies have linked the onset and treatment of DKD with gut microbiota. On the one hand, due to the change of the physical and chemical properties of the intestinal microenvironment in DKD state, the intestinal microbiota of patients is disturbed (5)(6)(7). These changes include the predicted function of gut microbiota, a significant reduction in the relative abundance of the butyrate-producing bacteria, SCFAs-producing bacteria and potential probiotics (5,7), an increase in genus Escherichia, Citrobacter and Klebsiella, and a decrease in of Roseburia (6).…”

Section: Introductionmentioning

confidence: 99%

“…On the one hand, due to the change of the physical and chemical properties of the intestinal microenvironment in DKD state, the intestinal microbiota of patients is disturbed (5)(6)(7). These changes include the predicted function of gut microbiota, a significant reduction in the relative abundance of the butyrate-producing bacteria, SCFAs-producing bacteria and potential probiotics (5,7), an increase in genus Escherichia, Citrobacter and Klebsiella, and a decrease in of Roseburia (6). Abnormal gut microbiota can damage the kidneys by activating the intrarenal reninangiotensin system and producing harmful metabolites (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice

et al. 2022

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BackgroundDiabetic kidney disease (DKD), as a serious microvascular complication of diabetes, has limted treatment options. It is reported that the Sacubitril/Valsartan (Sac/Val) can improve kidney function, and the disordered gut microbiota and part of its metabolites are related to the development of DKD. Therefore, we aim to explore whether the effect of Sac/Val on DKD is associated with the gut microbiota and related plasma metabolic profiles.MethodsMale C57BL/6J mice were randomly divided into 3 groups: Con group (n = 5), DKD group (n = 6), and Sac/Val group (n = 6) . Sac/Val group was treated with Sac/Val solution. The intervention was given once every 2 days for 6 weeks. We measured the blood glucose and urine protein level of mice at different times. We then collected samples at the end of experiment for the 16s rRNA gene sequencing analysis and the untargeted plasma metabonomic analysis.ResultsWe found that the plasma creatinine concentration of DKD-group mice was significantly higher than that of Con-group mice, whereas it was reduced after the Sac/Val treatment. Compared with DKD mice, Sac/Val treatment could decrease the expression of indicators related to EndMT and renal fibrosis like vimentin, collagen IV and fibronectin in kidney. According to the criteria of LDA ≥ 2.5 and p<0.05, LefSe analysis of gut microbiota identified 13 biomarkers in Con group, and 33 biomarkers in DKD group, mainly including Prevotella, Escherichia_Shigella and Christensenellaceae_R_7_group, etc. For the Sac/Val group, there were 21 biomarkers, such as Bacteroides, Rikenellaceae_RC9_gut_group, Parabacteroides, Lactobacillus, etc. Plasma metabolomics analysis identified a total of 648 metabolites, and 167 important differential metabolites were screened among groups. KEGG pathway of tryptophan metabolism: M and bile secretion: OS had the highest significance of enrichment.ConclusionsSac/Val improves the renal function of DKD mice by inhibiting renal fibrosis. This drug can also regulate gut microbiota in DKD mice.

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Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy

Cited by 40 publications

References 60 publications

Specific alterations of gut microbiota in diabetic microvascular complications: A systematic review and meta-analysis

Specific alterations of gut microbiota in diabetic microvascular complications: A systematic review and meta-analysis

Gut microbiota and its metabolites – molecular mechanisms and management strategies in diabetic kidney disease

Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice

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