The Specific Alteration of Gut Microbiota in Diabetic Kidney Diseases—A Systematic Review and Meta-Analysis

Abstract

BackgroundEmerging evidence indicates that gut dysbiosis is involved in the occurrence and development of diabetic kidney diseases (DKD). However, the key microbial taxa closely related to DKD have not been determined.MethodsPubMed, Web of Science, Cochrane, Chinese Biomedical Databases, China National Knowledge Internet, and Embase were searched for case-control or cross-sectional studies comparing the gut microbiota of patients with DKD and healthy controls (HC) from inception to February 8, 2022, and random/fixed-effects meta-analysis on the standardized mean difference (SMD) were performed for alpha diversity indexes between DKD and HC, and beta diversity indexes and the relative abundance of gut microbiota were extracted and summarized qualitatively.ResultsA total of 16 studies (578 patients with DKD and 444 HC) were included. Compared to HC, the bacterial richness of patients with DKD was significantly decreased, and the diversity indexes were decreased but not statistically, companying with a distinct beta diversity. The relative abundance of phylum Proteobacteria, Actinobacteria, and Bacteroidetes, family Coriobacteriaceae, Enterobacteriaceae, and Veillonellaceae, genus Enterococcus, Citrobacter, Escherichia, Klebsiella, Akkermansia, Sutterella, and Acinetobacter, and species E. coli were enriched while that of phylum Firmicutes, family Lachnospiraceae, genus Roseburia, Prevotella, and Bifidobacterium were depleted in patients with DKD.ConclusionsThe gut microbiota of patients with DKD may possess specific features characterized by expansion of genus Escherichia, Citrobacter, and Klebsiella, and depletion of Roseburia, which may contribute most to the alterations of their corresponding family and phylum taxa, as well as the bacterial diversity and composition. These microbial taxa may be closely related to DKD and serve as promising targets for the management of DKD.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021289863.

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

“…Recently, Klebsiella was demonstrated to be increased in DKD (63), which was proven to be increased in DC when compared to HC in this study. Microbiota symbiosis helped regulate metabolism and reduce the risk of DM.…”

“…Klebsiella is a natural inhabitant of the gastrointestinal tract microbiome of healthy humans and animals, but it often causes extraintestinal infections, including urinary tract infections, pneumoniae and septicemia ( 62 ). Recently, Klebsiella was demonstrated to be increased in DKD ( 63 ), which was proven to be increased in DC when compared to HC in this study.…”

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“…For instance, as it comes to DKD, it commonly appears that Lactobacillus and Akkermansia reduce, leading to the decrease in short-chain fatty acids (SCFAs) [ 32 ]; conversely, Bacteroides , Paraprevotella , Oscillibacter , and Lachnoclostridium rise, leading to the increase in TMAO, LPS, phenyl sulfate (PS), and indoxyl sulfate (IS). SCFAs have been reported to have multiple beneficial regulatory roles in DKD through inhibiting oxidative stress and inflammation to recover renal function [ 25 , 33 ]. On the contrary, TMAO, LPS, PS, and IS have been suggested to contribute to renal dysfunction by activating the renin–angiotensin–aldosterone system (RAAS) and the endothelin system, and then inducing insulin resistance, inflammation, oxidative stress, and fibrosis [ 34 , 35 ].…”

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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).…”

“…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).…”