A Comparative Study of the Gut Microbiota Associated with Immunoglobulin A Nephropathy and Membranous Nephropathy

2020 ◽  
Author(s):  
shiren sun ◽  
Ruijuan Dong ◽  
Ming Bai ◽  
Jin Zhao ◽  
Di Wang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Membranous Nephropathy ◽  
Kidney Biopsy ◽  
Immunoglobulin A ◽  
Amplicon Sequencing ◽  
Healthy Controls ◽  
Immunoglobulin A Nephropathy ◽  
Positive Correlation ◽  
16S Rdna Amplicon Sequencing ◽  
The Oxford Classification

Abstract Background The pathogenesis of immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) is characterized by immune dysregulation, which is related to gut dysbiosis. The aim of the study was to compare the gut microbiota of patients with IgAN and MN versus healthy controls. We used 16S rDNA amplicon sequencing to investigate the bacterial communities of 44 patients with kidney biopsy-proven IgAN, 40 patients with kidney biopsy-proven MN, and 30 matched healthy controls (HC). Results The abundance of Escherichia-Shigella and Defluviitaleaceae_incertae_sedis were significantly higher in IgAN than in HC, whereas lower abundances were observed for Roseburia, Lachnospiraceae_ unclassified, Clostridium_sensu_stricto_1, and Fusobacterium . Furthermore, the abundance of Escherichia-Shigella, Peptostreptococcaceae_incertae_sedis , Streptococcus, and Enterobacteriaceae_ unclassified increased, while that of Lachnospira, Lachnospiraceae_ unclassified, Clostridium_sensu_stricto_1, and Veillonella decreased in MN. The abundance of Megasphaera and Bilophila was higher, whereas that of Megamonas, Veillonella, Klebsiella, and Streptococcus was lower in patients with IgAN than in those with MN. Analysis of the correlations showed that in the IgAN group, Prevotella was positively correlated, while Klebsiella , Citrobacter, and Fusobacterium were negatively correlated with the level of serum albumin. Positive correlation also existed between Bilophila and Crescents in the Oxford classification of IgAN. In the MN group, negative correlation was observed between Escherichia-Shigella and proteinuria, Bacteroides and Klebsiella showed positive correlation with the MN stage. Conclusions Patients with IgAN and MN exhibited gut microbial signatures distinct from healthy controls. Our study suggests the potential of gut microbiota as specific biomarker and contributor in the pathogenesis of IgAN and MN.

scholarly journals Gut microbiota in Immunoglobulin A Nephropathy: a Malaysian Perspective

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Agni Nhirmal Kumar Sugurmar ◽  
Rozita Mohd ◽  
Shamsul Azhar Shah ◽  
Hui-min Neoh ◽  
Rizna Abdul Cader
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Immunoglobulin A ◽  
Alpha Diversity ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Control Cohort ◽  
Immunoglobulin A Nephropathy ◽  
Ckd Stage ◽  
The Mean

Abstract Introduction The alteration of the gut microbiome in the gut-kidney axis has been associated with a pro-inflammatory state and chronic kidney disease (CKD). A small-scaled Italian study has shown an association between the gut microbiome and Immunoglobulin A Nephropathy (IgAN). However, there is no data on gut microbiota in IgAN in the Asian population. This study compares the gut microbial abundance and diversity between healthy volunteers and Malaysian IgAN cohort. Methods A comparative cross-sectional study was conducted involving biopsy-proven IgAN patients in clinical remission with matched controls in a Malaysian tertiary centre. Demographic data, routine blood and urine results were recorded. Stool samples were collected and their DNA was extracted by 16S rRNA gene sequencing to profile their gut microbiota. Results Thirty-six IgAN patients (13 male; 23 female) with the mean age of 45.5 ± 13.4 years and median estimated glomerular filtration rate (eGFR) of 79.0 (62.1–92.2) mls/min/1.73m2 with median remission of 7 years were analysed and compared with 12 healthy controls (4 male; 8 female) with the mean age of 46.5 ± 13.5 years and eGFR of 86.5 (74.2–93.7) mls/min/1.73m2. Other demographic and laboratory parameters such as gender, ethnicity, body mass index (BMI), haemoglobin, serum urea and serum albumin were comparable between the two groups. There were no significant differences seen in the Operational Taxonomic Unit (OTU) and alpha diversity (Shannon index) between IgAN and healthy controls. Alpha diversity increased with increasing CKD stage (p = 0.025). Firmicutes/Bacteroidetes (F/B) ratio was low in both IgAN and healthy cohort. Fusobacteria phylum was significantly increased (p = 0.005) whereas Euryarchaoeota phylum was reduced (p = 0.016) in the IgAN group as compared to the control cohort. Conclusion Although we found no differences in OTU and alpha diversity between IgAN in remission and control cohort, there were some differences between the two groups at phylum level.

scholarly journals Integrated Fecal Microbiome and Serum Metabolomics Analysis Reveals Abnormal Changes in Rats with Immunoglobulin A Nephropathy and the Intervention Effect of Zhen Wu Tang

2021 ◽  
Vol 11 ◽  
Author(s):  
Jicheng Li ◽  
Yiwen Cao ◽  
Ruirui Lu ◽  
Honglian Li ◽  
Yu Pang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Renal Disease ◽  
Intestinal Microbiota ◽  
Renal Damage ◽  
Immunoglobulin A ◽  
Metabolic Phenotype ◽  
Immunoglobulin A Nephropathy ◽  
Metabolic Phenotypes ◽  
Potential Relationship ◽  
Rdna Sequencing

Immunoglobulin A nephropathy (IgAN), an autoimmune renal disease with complicated pathogenesis, is one of the principal reasons for end-stage renal disease in the clinic. Evidence has linked apparent alterations in the components of the microbiome and metabolome to renal disease in rats. However, thus far, there is insufficient evidence that supports the potential relationship between gut microbiome, circulating metabolites, and IgAN. This study was designed to probe the effects of IgAN on intestinal microecology and metabolic phenotypes and to understand the possible underlying mechanisms. Fecal and serum samples were collected from IgAN rats. Composition of the gut microbiota and biochemical changes in the metabolites was analyzed using 16S rDNA sequencing and untargeted metabolomics. The IgAN rats exhibited renal insufficiency and increased concentration of 24-h urine protein, in addition to deposition of IgA and IgG immune complexes in the kidney tissues. There was a disturbance in the balance of gut microbiota in IgAN rats, which was remarkably associated with renal damage. Marked changes in microbial structure and function were accompanied by apparent alterations in 1,403 serum metabolites, associated with the disorder of energy, carbohydrate, and nucleotide metabolisms. Administration of Zhen Wu Tang ameliorated microbial dysbiosis and attenuated the renal damage. Besides, treatment with Zhen Wu Tang modulated the metabolic phenotype perturbation in case of gut microbiota dysbiosis in IgAN rats. In conclusion, these findings provided a comprehensive understanding of the potential relationship between the intestinal microbiota and metabolic phenotypes in rats with IgAN. Elucidation of the intestinal microbiota composition and metabolic signature alterations could identify predictive biomarkers for disease diagnosis and progression, which might contribute to providing therapeutic strategies for IgAN.

scholarly journals The molecular mechanisms of inflammation and scarring in the kidneys of immunoglobulin A nephropathy

2021 ◽  
Author(s):  
Francesco Paolo Schena ◽  
Michele Rossini ◽  
Daniela Isabel Abbrescia ◽  
Gianluigi Zaza
Keyword(s):  
Molecular Mechanisms ◽  
Clinical Decision Making ◽  
Kidney Biopsy ◽  
Immunoglobulin A ◽  
Renal Tissue ◽  
Urinary Biomarkers ◽  
Specific Gene ◽  
Rna Seq ◽  
Immunoglobulin A Nephropathy ◽  
Renal Lesions

AbstractKidney biopsy is the cornerstone for the diagnosis of immunoglobulin A nephropathy (IgAN). The immunofluorescence technique evidences the IgA deposits in the glomeruli; the routine histology shows degree of active and chronic renal lesions. The spectrum of renal lesions is highly variable, ranging from minor or no detectable lesions to diffuse proliferative or crescentic lesions. Over the past three decades, renal transcriptomic studies have been performed on fresh or frozen renal tissue, and formalin-fixed paraffin-embedded kidney tissue specimens obtained from archival histological repositories. This paper aims to describe (1) the transcriptomic profiles of the kidney biopsy and (2) the potential urinary biomarkers that can be used to monitor the follow-up of IgAN patients. The use of quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), microarrays and RNA-sequencing (RNA-seq) techniques on renal tissue and separated compartments of the nephron such as glomeruli and tubule-interstitium has clarified many aspects of the renal damage in IgAN. Recently, the introduction of the single-cell RNA-seq techniques has overcome the limitations of the previous methods, making that it is possible to study the whole renal tissue without the dissection of the nephron segments; it also allows better analysis of the cell-specific gene expression involved in cell differentiation. These gene products could represent effective candidates for urinary biomarkers for clinical decision making. Finally, some of these molecules may be the targets of old drugs, such as corticosteroids, renin–angiotensin–aldosterone blockers, and new drugs such as monoclonal antibodies. In the era of personalized medicine and precision therapy, high-throughput technologies may better characterize different renal patterns of IgAN and deliver targeted treatments to individual patients.

scholarly journals Analysis of tissue PLA2R efficacy in evaluating the prognosis of idiopathic membranous nephropathy in the background of different serum anti-PLA2R levels

2020 ◽  
Author(s):  
Yuemeng Sun ◽  
Ping Lan ◽  
Jie Feng ◽  
Zhigang Wang ◽  
Chao Liu ◽  
...  
Keyword(s):  
Antibody Titer ◽  
Membranous Nephropathy ◽  
Kidney Biopsy ◽  
Clinical Presentation ◽  
Remission Rate ◽  
Antigen Expression ◽  
Predominant Role ◽  
Positive Correlation ◽  
Disease Prognosis ◽  
Antibody Levels

Objective To verify serum PLA2R antibody and glomerular PLA2R antigen expression in membranous nephropathy as well as to explore their relationship with clinical presentation and disease prognosis. Methods We retrospectively analyzed 155 patients clinical figures who were diagnosed with primary membranous nephropathy by kidney biopsy. Patients were divided into 6 groups according to their serum PLA2R antibody or glomerular PLA2R antigen positiveness and the level of serum PLA2R antibody titer. Both clinical features and pathological characteristics were recorded, and remission rate as well as time to response were compared among groups. Correlation between clinical figures and titer of PLA2R antibody or semi-quantity of PLA2R antigen were detected. Results Among patients with positive serum PLA2R antibody and tissue PLA2R antigen, higher baseline PLA2R antibody levels were associated with lower remission rate and longer remission time. A positive correlation between time to partial remission and serum PLA2R antibody titer was found. Among patients with serum PLA2R antibody titer <150U/L, there were shorter remission time in negative tissue PLA2R antigen group compared with positive tissue PLA2R antigen, and a positive correlation between time to complete remission and semi-quantity of tissue PLA2R antigen was found. Conclusion Both glomerular PLA2R antigen and serum PLA2R antibody play a role in disease presentation and prognosis in primary membranous nephropathy. Glomerular PLA2R antigen has a major role on disease prognosis when serum PLA2R antibody titer is less than 150U/L, while serum PLA2R antibody has predominant role in MN prognosis when serum PLA2R antibody titer is above 150 U/L.

scholarly journals Alterations in The Gut Microbiota and Metabolite Profiles in The Context of Neuropathic Pain

2021 ◽  
Author(s):  
Peng Chen ◽  
Chen Wang ◽  
Yan-na Ren ◽  
Zeng-jie Ye ◽  
Chao Jiang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Gut Microbiota ◽  
Amplicon Sequencing ◽  
Differentially Expressed ◽  
Metabolic Disturbances ◽  
Serum Metabolites ◽  
Genus Level ◽  
Metabolite Profiles ◽  
16S Rdna Amplicon Sequencing

Abstract The aim of this study was to explore the relationships among gut microbiota disturbances and serum and spinal cord metabolic disorders in neuropathic pain. 16S rDNA amplicon sequencing and serum and spinal cord metabolomics were used to identify alterations in the microbiota and metabolite profiles in the sham rats and the chronic constriction injury (CCI) model rats. Correlations between the abundances of gut microbiota components at the genus level, the levels of serum metabolites, and pain-related behavioural parameters were analysed. Ingenuity pathway analysis (IPA) was applied to analyse the interaction networks of the differentially expressed serum metabolites. First, we found that the composition of the gut microbiota was different between rats with CCI-induced neuropathic pain and sham controls. At the genus level, the abundances of Helicobacter, Phascolarctobacterium, Christensenella, Blautia, Streptococcus, Rothia and Lactobacillus were significantly increased, whereas the abundances of Ignatzschineria, Butyricimonas, Escherichia, AF12, and Corynebacterium were significantly decreased. Additionally, 72 significantly differentially expressed serum metabolites and 17 significantly differentially expressed spinal cord metabolites were identified between the CCI rats and the sham rats. Finally, correlation analysis showed that changes in the gut microbiota was significantly correlated with changes in serum metabolite levels, suggesting that dysbiosis of the gut microbiota is an important factor in modulating metabolic disturbances in the context of neuropathic pain. In conclusion, our research provides a novel perspective on the potential roles of the gut microbiota and related metabolites in neuropathic pain.

scholarly journals Pyruvate Might Bridge Gut Microbiota and Muscle Health in Aging Mice After Chronic High Dose of Leucine Supplementation

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuxiao Liao ◽  
Dan Li ◽  
Xiaolei Zhou ◽  
Zhao Peng ◽  
Zitong Meng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Amplicon Sequencing ◽  
Ultrasound Measurement ◽  
High Dose ◽  
Leucine Supplementation ◽  
Cross Sectional ◽  
Pyruvate Fermentation ◽  
Before And After ◽  
16S Rdna Amplicon Sequencing ◽  
Muscle Health

Background: The previous studies demonstrated that there might be complex and close relationships among leucine supplementation, gut microbiota, and muscle health, which still needs further investigation.Aims: This study aimed to explore the associations of gut microbiota with muscle health after leucine intake.Methods: In this study, 19-month-old male C57BL/6j mice (n = 12/group) were supplemented with ultrapure water, low dose of leucine (500 mg/kg·d), and high dose of leucine (1,250 mg/kg·d) for 12 weeks by oral gavage. The mice fecal samples in each group before and after supplementation were collected for baseline and endpoint gut microbiota analysis by using 16S rDNA amplicon sequencing. Meanwhile, ultrasound measurement, H&amp;E staining, myofiber cross-sectional area (CSA) measurement, and western blotting were performed in the quadriceps subsequently. The pyruvate levels were detected in feces.Results: Improvement in muscle of histology and ultrasonography were observed after both low and high dose of leucine supplementation. High dose of leucine supplementation could promote skeletal muscle health in aging mice via regulating AMPKα/SIRT1/PGC-1α. The richness and diversities of microbiota as well as enriched metabolic pathways were altered after leucine supplementation. Firmicutes-Bacteroidetes ratio was significantly decreased in high-leucine group. Moreover, pyruvate fermentation to propanoate I were negatively associated with differential species and the pyruvate levels were significantly increased in feces after high dose of leucine supplementation.Conclusions: Chronic high dose of leucine supplementation changed gut microbiota composition and increased pyruvate levels in the feces, which possibly provides a novel direction for promoting muscle health in aging mice.

scholarly journals Aberrant mucosal immunoreaction to tonsillar microbiota in immunoglobulin A nephropathy

2020 ◽  
Vol 36 (1) ◽  
pp. 75-86
Author(s):  
Hiroki Yamaguchi ◽  
Shin Goto ◽  
Nao Takahashi ◽  
Masafumi Tsuchida ◽  
Hirofumi Watanabe ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immunoglobulin A ◽  
Gel Filtration ◽  
Amplicon Sequencing ◽  
Enrichment Score ◽  
Immunoglobulin A Nephropathy ◽  
Recurrent Tonsillitis ◽  
Sorting Technique ◽  
Preferential Binding ◽  
Repertoire Sequencing

Abstract Background Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by mesangial polymeric IgA1 deposition. IgAN is believed to develop owing to aberrant mucosal immunoreaction against commensals in the tonsils. However, the exact interrelation between pathogenic IgA and mucosal microbiota in IgAN patients is unclear. Methods Biopsy-proven IgAN or recurrent tonsillitis (RT) patients who had undergone tonsillectomy were enrolled. We used 16S ribosomal RNA gene amplicon sequencing with a flow cytometry-based bacterial cell sorting technique) and immunoglobulin repertoire sequencing of the IgA heavy chain to characterize IgA-coated bacteria of the tonsillar microbiota (IgA-SEQ) and their corresponding IgA repertoire. Furthermore, we fractionated patient serum using gel-filtration chromatography and performed flow cytometry-based analysis of IgA binding to bacteria cultured from incised tonsils. Results Tonsillar proliferation-inducing ligand and B-cell activating factor levels were significantly higher in IgAN than in RT patients. IgA-SEQ for tonsillar microbiota revealed the preferential binding ability of IgA to Bacteroidetes in IgAN tonsils compared with those from RT patients. Expression of immunoglobulin heavy (IGH) constant alpha 1 with IGH variable 3–30 was significantly higher in IgAN than that in RT, and positively correlated with the IgA-coated enrichment score of Bacteroidetes. Serum polymeric IgA, comprising high levels of GdIgA1, exhibited considerable binding to Bacteroidetes strains cultured from the tonsils of IgAN patients. Conclusions These findings provide evidence that aberrant mucosal immune responses to tonsillar anaerobic microbiota, primarily consisting of members of the phylum Bacteroidetes, are involved in IgAN pathophysiology.

P0339URINE METABOLOMIC ASSAY IN EARLY IGA NEPHROPATHY PATIENTS REVEALS URINE GLYCINE AS A PROGNOSTIC BIOMARKER

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sehoon Park ◽  
Seung Hee Yang ◽  
Kwon Wook Joo ◽  
Jung-Hyun Kim ◽  
Dong Ki Kim
Keyword(s):  
Disease Control ◽  
Kidney Biopsy ◽  
Immunoglobulin A ◽  
Control Group ◽  
Healthy Controls ◽  
Urine Metabolites ◽  
Urine Concentrations ◽  
Glycine Cleavage ◽  
Function Range ◽  
Prognostic Prediction

Abstract Background and Aims A urine metabolomic biomarker from early immunoglobulin A nephropathy (IgAN) can be a useful tool for early detection or prognostic prediction of the disease. Method We profiled the urine metabolomes, using nuclear magnetic resonance (NMR) spectrometry, from 197 IgAN patients with eGFR ≥ 60 mL/min/1.73 m2, and the patients with same kidney function range but have diagnosis of membranous nephropathy (n=81) and minimal change disease (n=50) were included as the disease-control group. Additional 146 healthy controls who received routine health screenings and donated urine samples were included. We calculated the creatinine-adjusted urine concentrations of 27 urine metabolites. Urine metabolites specifically increased in urines from IgAN patients were identified, and their associations with the prognosis of the disease, determined with the outcome of eGFR 30% reduction from baseline, were investigated. Additional kidney biopsy samples from independent patients and controls were stained for molecules included in related biological process for experimental validation. Results Among the 15 metabolites higher in the urines from IgAN patients than those from the healthy controls, only glycine was the metabolite that the median level was significantly higher also than that of the disease-control group. We found that the higher levels of glycine, alanine, citrate, threonine, and valine were significantly associated with higher risks of 30% eGFR reduction in IgAN patients. Among the molecules related to metabolism of glycine, expressions of T and H proteins from glycine cleavage system were significantly reduced in the kidney biopsy slides from independent IgAN patients when compared to the controls. Conclusion Urine glycine may be a prognostic and pathophysiology-related biomarker of IgAN. A further study confirming the clinical usefulness and pathophysiologic significance of urine metabolites in IgAN patients is warranted.

scholarly journals IFI27 Is a Useful Genetic Marker for Diagnosis of Immunoglobulin A Nephropathy and Membranous Nephropathy Using Peripheral Blood

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153252 ◽  
Author(s):  
Yasuyuki Nagasawa ◽  
Daisuke Okuzaki ◽  
Eri Muso ◽  
Ryohei Yamamoto ◽  
Maki Shinzawa ◽  
...  
Keyword(s):  
Genetic Marker ◽  
Peripheral Blood ◽  
Membranous Nephropathy ◽  
Immunoglobulin A ◽  
Immunoglobulin A Nephropathy
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