Gut Microbiome Characteristics in IgA Nephropathy: Qualitative and Quantitative Analysis from Observational Studies

Abstract

BackgroundRecent data indicate the importance of gut-kidney axis in the pathogenesis of Immunoglobulin A nephropathy (IgAN). Growing evidence suggests the alterations of diversity and composition of gut microbiome among patients with IgAN, however, the details are not yet fully understood.MethodsEligible studies comparing the gut microbiome between patients with IgAN and non-IgAN individuals were systematically searched from PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and ClinicalTrials.gov. The primary outcomes were alpha- and beta-diversity, and the differences in gut microbiota composition between patients with IgAN and non-IgAN persons. Qualitative analysis and meta-analysis were performed according to available data.ResultsEleven cross-sectional studies, including 409 patients with IgAN and 243 healthy controls, were enrolled. No significant differences in the diversity and enrichment of gut bacteria were found between IgAN and healthy individuals, whereas the beta-diversity consistently showed significant microbial dissimilarities among the two groups. Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia were the dominant phyla, however, no significant differences were found between IgAN patients and healthy controls at the phylum level. The genera, Streptococcus and Paraprevotella showed a higher proportion in patients with IgAN compared to healthy individuals, whereas Fusicatenibacter showed a lower abundance according to meta-analysis. Qualitative analyses suggested that Escherichia-Shigella might be increased in IgAN patients; the genera, Clostridium, Prevotella 9,and Roseburia, members of Ruminococcaceae and Lachnospiraceae families, were likely to have decreased abundances in patients with IgAN compared to healthy individuals.ConclusionGut microbiota dysbiosis was demonstrated in IgAN, which might be involved in the pathogenesis of IgAN. Further studies are needed to confirm the findings of this study, due to the substantial heterogeneity.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42022304034).

Kidney Diseases Associated With Inflammatory Bowel Disease: Impact of Chronic Histologic Damage, Treatments, and Outcomes

“… 23 , 24 The gut-kidney axis hypothesis supports a key role for imbalances between immunity and microbiota in the development or exacerbation of IgAN. 25 , 26 Gut microbiota can lead to B cell activation via B cell activation factor, and this overstimulation promotes a significant shift from IgA2 to IgA1 production. 27 , 28 In addition, an aberrant O -linked glycosylation of IgA is observed in patients with CD.…”

The Effects of Specific Gut Microbiota and Metabolites on IgA Nephropathy—Based on Mendelian Randomization and Clinical Validation

“…Most cross-sectional study results lean towards higher levels of Actinobacteria in the feces of IgAN patients, while Zhong et al [ 26 ] reported significantly lower abundance in IgAN patients. A bibliometric study [ 13 ] found no significant difference in the richness of feces between IgAN patients and healthy controls. This discrepancy may be due to the considerable heterogeneity of the included literature.…”

“…The overproduction of abnormally glycosylated IgA antibodies by intestinal mucosal immune cells leads to a cascade of subsequent multiple immune attacks [ 8 , 9 , 10 ]. It has been demonstrated that gut microbiota and metabolites play a crucial role in inducing IgAN mucosal immunity [ 11 , 12 , 13 ]. Metabolites released by dysregulated flora, such as indoxyl sulfate, p -cresyl sulfate, indole-3-acetic acid, trimethylamine N-oxide (TMAO), and phenylacetylglutamine, may compromise the integrity of the intestinal barrier [ 11 , 14 ].…”

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

“…For qualitative analysis, the results of each prespecified outcome were summarized and presented as stacked histograms. A funnel R script was adopted to explore differential bacteria between different groups at the significance levels of 80% and 95%, through calculating a binomial Poisson distribution score2 (18). For meta-analysis, standardized mean difference (SMD) and 95% confidence intervals (CIs) were calculated to evaluate the differences in diversity indices and relative abundances of gut bacteria between DKD and non-DKD groups.…”