Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives

Lin, Jiaran; Wang, Ziting; Sun, Jian; Yang, Yingying; Li, Xue-Xin; Wang, Xinru; Shi, Yonghui; Zhu, Yunlong; Wang, Ruiting; Wang, Mina; Xie, Feiyu; Wei, Ping; Liao, Ziqi

doi:10.4239/wjd.v13.i4.308

Cited by 23 publications

(20 citation statements)

References 75 publications

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“…However, therapies based on these mechanisms have limited effects; more researches about DKD pathogenesis are essential and may provide new insights into treating DKD. Intriguingly, the gut microbiota as a novel intervention for diabetes and its complications, such as DKD, is now attracting more and more attention (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associatied with increasing effect on the gut microbiota in db/db mice

Chen²,

Yang³

et al. 2023

Front. Endocrinol.

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BackgroundThe intestinal microbiota disorder gradually aggravates during the progression of diabetes. Dapagliflozin (DAPA) can improve diabetes and diabetic kidney disease(DKD). However, whether the gut microbiota plays a role in the protection of DAPA for DKD remains unclear.MethodsTo investigate the effects of DAPA on DKD and gut microbiota composition during disease progression, in our study, we performed 16S rRNA gene sequencing on fecal samples from db/m mice (control group), db/db mice (DKD model group), and those treated with DAPA (treat group) at three timepoints of 14weeks\18weeks\22weeks.ResultsWe found that DAPA remarkably prevented weight loss and lowered fasting blood glucose in db/db mice during disease progression, eventually delaying the progression of DKD. Intriguingly, the study strongly suggested that there is gradually aggravated dysbacteriosis and increased bile acid during the development of DKD. More importantly, comparisons of relative abundance at the phylum level and partial least squares-discriminant analysis (PLS-DA) plots roughly reflected that the effect of DAPA on modulating the flora of db/db mice increased with time. Specifically, the relative abundance of the dominant Firmicutes and Bacteroidetes was not meaningfully changed among groups at 14 weeks as previous studies described. Interestingly, they were gradually altered in the treat group compared to the model group with a more protracted intervention of 18 weeks and 22 weeks. Furthermore, the decrease of Lactobacillus and the increase of norank_f:Muribaculaceae could account for the differences at the phylum level observed between the treat group and the model group at 18 weeks and 22 weeks.ConclusionWe firstly found that the protective effect of DAPA on DKD may be related to the dynamic improvement of the gut microbiota over time, possibly associated with the impact of DAPA on the bile acid pool and its antioxidation effect.

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Section: Introductionmentioning

confidence: 99%

Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associatied with increasing effect on the gut microbiota in db/db mice

Chen²,

Yang³

et al. 2023

Front. Endocrinol.

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“…G_ Odoribacter , g_ ruminiclorstridium , g_ Adlercreutzia and G_ LachnospiraceaeNK4A136. The increase of this group and g_u_ruminococcaceae nk4a214 group accelerated the process of DKD ( 59 ). In prediabetes, or impaired glucose tolerance (IGT), researchers observed a significant decrease in Clostridium ( 60 ) and butyric-producing bacteria ( 39 ) in the intestinal flora, while there was an increase in Dolella .…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota diversity in middle-aged and elderly patients with end-stage diabetic kidney disease

Chen¹,

Zhu²,

Yang³

et al. 2022

Ann Transl Med

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Background: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD), but the mechanism between DKD and ESRD remains unclear. Some experts have put forward the "microbial-centered ESRD development theory", believing that the bacterial load caused by gut microecological imbalance and uremia toxin transfer are the core pathogenic links. The purpose of this study was to analyze the genomic characteristics of gut microbiota in patients with ESRD, specifically DKD or non-diabetic kidney disease (NDKD). Methods:In this cross-sectional study, patients with ESRD were recruited in a community, including 22 DKD patients and 22 NDKD patients matched using gender and age. Fecal samples of patients were collected for 16S rDNA sequencing and gut microbiota analysis. The distribution structure, diversity, and abundance of microflora in DKD patients were analyzed by constructing species evolutionary trees and analyzing alpha diversity, beta diversity, and linear discriminant analysis effect size (LEfSe). Results:The results of our study showed that there were statistically significant differences in the richness and species of gut microbiota at the total level between DKD patients and NDKD patients. The analysis of genus level between the two groups showed significant differences in 16 bacterial genera. Among them, Oscillibacter, Bilophila, UBA1819, Ruminococcaceae UCG-004, Anaerotruncus, Ruminococcaceae, and Ruminococcaceae NK4A214 bacteria in DKD patients were higher than those in NDKD patients.Conclusions: 16S rDNA sequencing technology was used in this study to analyze the characteristics of intestinal flora in ESRD patients with or without diabetes. We found that there was a significant difference in the intestinal flora of ESRD patients caused by DKD and NDKD, suggesting that these may be potential causative bacteria for the development of ERSD in DKD patients.

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“…Accumulating evidence has demonstrated that alterations of composition and function in gut microbiota were correlated with increased risk of the occurrence and development of diabetes and its associated complications (36). This review was designed to comprehensively characterize the alterations of gut microbiome in DKD, by comparing with diabetes, NDKD, and healthy controls.…”

Section: Discussionmentioning

confidence: 99%

A systematic review and meta-analysis of gut microbiota in diabetic kidney disease: Comparisons with diabetes mellitus, non-diabetic kidney disease, and healthy individuals

et al. 2022

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BackgroundGut microbiota has been reported to play an important role in diabetic kidney disease (DKD), however, the alterations of gut bacteria have not been determined.MethodsStudies comparing the differences of gut microbiome between patients with DKD and non-DKD individuals using high-throughput sequencing technology, were systematically searched and reviewed. Outcomes were set as gut bacterial diversity, microbial composition, and correlation with clinical parameters of DKD. Qualitative data were summarized and compared through a funnel R script, and quantitative data were estimated by meta-analysis.ResultsA total of 15 studies and 1640 participants were included, the comparisons were conducted between DKD, diabetes mellitus (DM), non-diabetic kidney disease (NDKD), and healthy controls. There were no significant differences of α-diversity between DKD and DM, and between DKD and NDKD, however, significant lower microbial richness was found in DKD compared to healthy controls. Different bacterial compositions were found between DKD and non-DKD subjects. The phylum Actinobacteria were found to be enriched in DKD compared to healthy controls. At the genus level, we found the enrichment of Hungatella, Bilophila, and Escherichia in DKD compared to DM, patients with DKD showed lower abundances of Faecalibacterium compared to those with NDKD. The genera Butyricicoccus, Faecalibacterium, and Lachnospira were depleted in DKD compared to healthy controls, whereas Hungatella, Escherichia, and lactobacillus were significantly enriched. The genus Ruminococcus torques group was demonstrated to be inversely correlated with estimated glomerular filtration rate of DKD.ConclusionsGut bacterial alterations was demonstrated in DKD, characterized by the enrichment of the genera Hungatella and Escherichia, and the depletion of butyrate-producing bacteria, which might be associated with the occurrence and development of DKD. Further studies are still needed to validate these findings, due to substantial heterogeneity.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022340870.

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Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives

Cited by 23 publications

References 75 publications

Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associatied with increasing effect on the gut microbiota in db/db mice

Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associatied with increasing effect on the gut microbiota in db/db mice

Gut microbiota diversity in middle-aged and elderly patients with end-stage diabetic kidney disease

A systematic review and meta-analysis of gut microbiota in diabetic kidney disease: Comparisons with diabetes mellitus, non-diabetic kidney disease, and healthy individuals

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