This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Wei Qin
Sichuan University West China Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4246-5431
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Immunoglobulin A nephropathy (IgAN) is a common autoimmune glomerular disease, the classic manifestations of which are hematuria and proteinuria. The pathogenesis of IgAN has been associated with dysregulated intestinal mucosal immunity. However, whether gut microbial modifications play a part in IgAN remains unclear.
Methods
Blood and fecal samples were collected from 52 IgAN patients and 25 healthy controls (HCs). The gut microbiome was analyzed by 16S ribosomal RNA (rRNA) gene sequencing, followed by analyses of gut microbiota composition. Furthermore, the levels of galactose-deficient IgA1 (Gd-IgA1), soluble cluster of differentiation 14 (sCD14), lipopolysaccharide binding protein (LBP), intercellular adhesion molecule-1 (ICAM-1), and C-reactive protein (CRP) was quantified by enzyme-linked immunosorbent assay (ELISA).
Results
Substantial differences in gut microbiota were found between IgAN patients and HCs (P < 0.05). The abundance of pathogenic bacteria (Bacteroides and Escherichia-Shigella) was significantly higher in IgAN patients than in HCs, while that of beneficial strains (Bifidobacterium and Blautia spp.) was lower. Higher proportions of Escherichia-Shigella and lower proportions of Bifidobacterium spp. were observed in IgAN patients with a high urine RBC count (≥ 10/HP) and proteinuria (≥ 1 g/24 h) levers. Spearman’s correlation analysis was used to assess the association between gut microbiota and biomarkers in IgAN patients. The results showed that the genus Prevotella 7 was negatively correlated with Gd-IgA1, LBP, sCD14, and ICAM-1, while Bifidobacterium spp. presented a significant inverse relationship with LBP and Gd-IgA1. Additionally, Escherichia-Shigella was negatively correlated with Prevotella 7.
Conclusions
In IgAN patients, gut modifications were characterized by an increase in the numbers of pathogenic bacteria and a reduction in the levers of beneficial bacteria. Our results suggest that disturbance of the intestinal microflora might play a critical part in the severity of IgAN, and may be a potential therapeutic target.
Keywords
IgA nephropathy, Modifications of abundances of bacteria, 16S ribosomal RNA, blood biomarkers, severity
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Wei Qin
Sichuan University West China Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4246-5431
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 09 Jul, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Urology & Nephrology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Immunoglobulin A nephropathy (IgAN) is a common autoimmune glomerular disease, the classic manifestations of which are hematuria and proteinuria. The pathogenesis of IgAN has been associated with dysregulated intestinal mucosal immunity. However, whether gut microbial modifications play a part in IgAN remains unclear.
Methods
Blood and fecal samples were collected from 52 IgAN patients and 25 healthy controls (HCs). The gut microbiome was analyzed by 16S ribosomal RNA (rRNA) gene sequencing, followed by analyses of gut microbiota composition. Furthermore, the levels of galactose-deficient IgA1 (Gd-IgA1), soluble cluster of differentiation 14 (sCD14), lipopolysaccharide binding protein (LBP), intercellular adhesion molecule-1 (ICAM-1), and C-reactive protein (CRP) was quantified by enzyme-linked immunosorbent assay (ELISA).
Results
Substantial differences in gut microbiota were found between IgAN patients and HCs (P < 0.05). The abundance of pathogenic bacteria (Bacteroides and Escherichia-Shigella) was significantly higher in IgAN patients than in HCs, while that of beneficial strains (Bifidobacterium and Blautia spp.) was lower. Higher proportions of Escherichia-Shigella and lower proportions of Bifidobacterium spp. were observed in IgAN patients with a high urine RBC count (≥ 10/HP) and proteinuria (≥ 1 g/24 h) levers. Spearman’s correlation analysis was used to assess the association between gut microbiota and biomarkers in IgAN patients. The results showed that the genus Prevotella 7 was negatively correlated with Gd-IgA1, LBP, sCD14, and ICAM-1, while Bifidobacterium spp. presented a significant inverse relationship with LBP and Gd-IgA1. Additionally, Escherichia-Shigella was negatively correlated with Prevotella 7.
Conclusions
In IgAN patients, gut modifications were characterized by an increase in the numbers of pathogenic bacteria and a reduction in the levers of beneficial bacteria. Our results suggest that disturbance of the intestinal microflora might play a critical part in the severity of IgAN, and may be a potential therapeutic target.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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