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Systematic Microbiome Dysbiosis Is Associated with IgA Nephropathy.

ABSTRACT: IgA nephropathy (IgAN) is reportedly associated with microbial dysbiosis. However, the microbiome dysregulation of IgAN patients across multiple niches remains unclear. To gain a systematic understanding of microbial dysbiosis, we conducted large-scale 16S rRNA gene sequencing in IgAN patients and healthy volunteers across 1,732 oral, pharynx, gut, and urine samples. We observed a niche-specific increase of several opportunistic pathogens, including Bergeyella and Capnocytophaga in the oral and pharynx, whereas some beneficial commensals decreased in IgAN patients. Similar alterations were also observed in the early versus advanced stage of chronic kidney disease (CKD) progression. Moreover, Bergeyella, Capnocytophaga, and Comamonas in the oral and pharynx were positively associated with creatinine and urea, indicating renal lesions. Random forest classifiers were developed by using the microbial abundance to predict IgAN, achieving an optimal accuracy of 0.879 in the discovery phase and 0.780 in the validation phase. IMPORTANCE This study provides microbial profiles of IgAN across multiple niches and underlines the potential of these biomarkers as promising, noninvasive tools with which to differentiate IgAN patients for clinical applications.

SUBMITTER: Cai F

PROVIDER: S-EPMC10269816 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Systematic Microbiome Dysbiosis Is Associated with IgA Nephropathy.

Cai Fengtao F Zhou Chenfen C Jiao Na N Liang Xinling X Ye Zhiming Z Chen Wei W Yang Qiongqiong Q Peng Hui H Tang Ying Y Niu Chaoqun C Zhao Guoping G Wang Zefeng Z Zhang Guoqing G Yu Xueqing X

Microbiology spectrum 20230525 3

IgA nephropathy (IgAN) is reportedly associated with microbial dysbiosis. However, the microbiome dysregulation of IgAN patients across multiple niches remains unclear. To gain a systematic understanding of microbial dysbiosis, we conducted large-scale 16S rRNA gene sequencing in IgAN patients and healthy volunteers across 1,732 oral, pharynx, gut, and urine samples. We observed a niche-specific increase of several opportunistic pathogens, including <i>Bergeyella</i> and <i>Capnocytophaga</i> in ...[more]

PMID: 37227280

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Project description:BackgroundRecently, a few studies have indicated a relationship between the gut microbiota and IgA nephropathy (IgAN). Whether the gut microbiota participates in the pathogenesis of IgAN and whether probiotics are effective in treating IgAN are still controversial. Therefore, this study aimed to identify the differences in the structure of the gut microbiota between IgAN and controls and to evaluate the efficacy and mechanism of probiotics in the treatment of IgAN.MethodsTo address this question, 35 IgAN patients and 25 healthy volunteers were enrolled, and a mouse IgAN model was also constructed. The stool microbes were analyzed by 16S rRNA high-throughput sequencing to identify the differential strains between IgAN and healthy controls. The impact of probiotics on the structure of the intestinal flora and the efficacy of the probiotics in the treatment of IgAN were evaluated.ResultsAlthough the microflora structure of mice and humans was not the same, both patients and mice with IgAN exhibited gut microbiota dysbiosis, with all subjects presenting an evident decrease in Bifidobacterium levels. The Bifidobacterium proportion was negatively correlated with proteinuria and hematuria levels, indicating that the decreased Bifidobacterium abundance could be related to IgAN severity. Probiotic treatment containing Bifidobacterium in IgAN mice could significantly alleviate gut dysbiosis, specifically by increasing the proportion of beneficial bacteria and reducing the abundance of potentially pathogenic bacteria. Moreover, both probiotics and their metabolites, short-chain fatty acids (SCFAs), could attenuate IgAN clinicopathological manifestations by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway.ConclusionsSupplementation with probiotics mainly containing Bifidobacterium could markedly improve gut dysbiosis in IgAN. Moreover, both probiotics and their SCFA metabolites could attenuate the clinicopathological manifestations of IgAN by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway. Therefore, probiotics have potential as an adjunctive therapy for IgAN.

Project description:BackgroundIgA nephropathy (IgAN) has been associated with gut dysbiosis, intestinal membrane disruption, and translocation of bacteria into blood. Our study aimed to understand the association of gut and blood microbiomes in patients with IgAN in relation to healthy controls.MethodsWe conducted a case-control study with 20 patients with progressive IgAN, matched with 20 healthy controls, and analyzed bacterial DNA quantitatively in blood using 16S PCR and qualitatively in blood and stool using 16S metagenomic sequencing. We conducted between-group comparisons as well as comparisons between the blood and gut microbiomes.ResultsHigher median 16S bacterial DNA in blood was found in the IgAN group compared with the healthy controls group (7410 versus 6030 16S rDNA copies/μl blood, P=0.04). α- and β-Diversity in both blood and stool was largely similar between the IgAN and healthy groups. In patients with IgAN, in comparison with healthy controls, we observed higher proportions of the class Coriobacteriia and species of the genera Legionella, Enhydrobacter, and Parabacteroides in blood, and species of the genera Bacteroides, Escherichia-Shigella, and some Ruminococcus in stool. Taxa distribution were markedly different between the blood and stool samples of each subject in both IgAN and healthy groups, without any significant correlation between corresponding gut and blood phyla.ConclusionsImportant bacterial taxonomic differences, quantitatively in blood and qualitatively in both blood and stool samples, that were detected between IgAN and healthy groups warrant further investigation into their roles in the pathogenesis of IgAN. Although gut bacterial translocation into blood may be one of the potential sources of the blood microbiome, marked taxonomic differences between gut and blood samples in each subject in both groups confirms that the blood microbiome does not directly reflect the gut microbiome. Further research is needed into other possible sites of origin and internal regulation of the blood microbiome.

Project description:BackgroundImmunoglobulin A nephropathy (IgAN) is the most common type of primary glomerular disease in adults worldwide. Several studies have reported that galactose-deficient IgA1 (Gd-IgA1) is involved in the pathogenesis of IgAN.MethodsThirty-five patients with IgAN diagnosed with renal biopsy for the first time served as the experimental group, who were hospitalized in our department. Twenty normal healthy cases in the physical examination center of our hospital served as the control group. Then the levels of Gd-IgA1 in serum and urine, and intestinal mucosal barrier injury indexes [diamine oxidase (DAO), serum soluble intercellular adhesion molecule-1 (sICAM-1), D-lactate (D-LAC), and lipopolysaccharide (LPS)] and inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)] in the serum samples were detected. Fecal samples were collected to detect intestinal microbiota using 16 s rDNA sequencing. Then, we assessed possible correlations among clinical and laboratory findings.ResultsIn patients with IgAN, the levels of Gd-IgA1 both in the serum and urine were higher than that of the healthy control. Furthermore, urine Gd-IgA1 level was positively correlated with the serum creatinine level, 24 h urine protein, and M, S, and T parameters in the Oxford classification. ROC curve analysis showed that urine Gd-IgA1 has a greater diagnostic value (AUC = 0.9714, 95% CI, 0.932-1; P < 0.0001) for IgAN. The best cutoff value for urine Gd-IgA1 was 0.745 ng·l/ml·μmol (sensitivity, 94%; specificity, 95%). The intestinal mucosal barrier damage indexes (DAO, sICAM-1, D-LAC, and LPS) were increased in the patients with IgAN, which were positively correlated with Gd-IgA1 levels (P < 0.05) both in serum and urine. The levels of inflammatory factors in the patients with IgAN were increased. 16 s rDNA analysis showed that the intestinal microbiota in these patients was disordered compared to that observed in the healthy subjects. Actinobacteria, Bifidobacterium, Blautia, Bifidobacteriaceae, and Bifidobacteriales were decreased and Shigella was increased in IgAN. The decreased populations of these flora were negatively and significantly correlated with urine Gd-IgA1 and the levels of DAO, sICAM-1, D-LAC, and LPS.ConclusionThe urine Gd-IgA1 levels may be a non-invasive biological marker for evaluating kidney injury in IgAN. Gut flora dysbiosis and intestinal barrier dysfunction may be involved in Gd-IgA1 expression.

Dataset Information

Systematic Microbiome Dysbiosis Is Associated with IgA Nephropathy.

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Systematic Microbiome Dysbiosis Is Associated with IgA Nephropathy.

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