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The bladder microbiome, metabolome, cytokines, and phenotypes in patients with systemic lupus erythematosus

Fengping Liu, Jingjie Du, Qixiao Zhai, Jialin Hu, Aaron W. Miller, Tianli Ren, Yangkun Feng, Peng Jiang, Lei Hu, Jiayi Sheng, Chaoqun Gu, Ren Yan, View ORCID ProfileLongxian Lv, View ORCID ProfileAlan J. Wolfe, Ninghan Feng
doi: https://doi.org/10.1101/2022.01.13.476281
Fengping Liu
1Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, China
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Jingjie Du
2Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
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Qixiao Zhai
3State Key Laboratory of Food Science and Technology and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, China
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Jialin Hu
4Department of Urology, Affiliated Wuxi No.2 Hospital, Nanjing Medical University, Wuxi, Jiangsu, 214000, China
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Aaron W. Miller
5Glickman Urological and Kidney Institute, Cleveland Clinicgrid. 239578.2, Cleveland, Ohio, USA
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Tianli Ren
6Department of Rheumatology, Affiliated Wuxi No. 2 Hospital, Nanjing Medical University, Wuxi, 214000, China
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Yangkun Feng
4Department of Urology, Affiliated Wuxi No.2 Hospital, Nanjing Medical University, Wuxi, Jiangsu, 214000, China
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Peng Jiang
4Department of Urology, Affiliated Wuxi No.2 Hospital, Nanjing Medical University, Wuxi, Jiangsu, 214000, China
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Lei Hu
4Department of Urology, Affiliated Wuxi No.2 Hospital, Nanjing Medical University, Wuxi, Jiangsu, 214000, China
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Jiayi Sheng
4Department of Urology, Affiliated Wuxi No.2 Hospital, Nanjing Medical University, Wuxi, Jiangsu, 214000, China
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Chaoqun Gu
4Department of Urology, Affiliated Wuxi No.2 Hospital, Nanjing Medical University, Wuxi, Jiangsu, 214000, China
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Ren Yan
7Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China
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Longxian Lv
7Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China
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  • For correspondence: lvlongxian@aliyun.com awolfe@luc.edu n.feng@njmu.edu.cn
Alan J. Wolfe
2Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
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  • For correspondence: lvlongxian@aliyun.com awolfe@luc.edu n.feng@njmu.edu.cn
Ninghan Feng
4Department of Urology, Affiliated Wuxi No.2 Hospital, Nanjing Medical University, Wuxi, Jiangsu, 214000, China
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  • For correspondence: lvlongxian@aliyun.com awolfe@luc.edu n.feng@njmu.edu.cn
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Abstract

Background and aims Emerging studies reveal a unique bacterial community in the human bladder, with alteration of composition associated to disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by frequent impairment of the kidney. Here, we explored the bladder microbiome, metabolome, and cytokine profiles in SLE patients, as well as correlations between microbiome and metabolome, cytokines, and disease profiles.

Methods and materials We recruited a cohort of 50 SLE patients and 50 individually matched asymptomatic controls. We used transurethral catheterization to collect urine samples, 16S rRNA gene sequencing to profile bladder microbiomes, and LC-MS/MS to perform untargeted metabolomic profiling.

Results Compared to controls, SLE patients possessed a unique bladder microbial community and increased alpha diversity. These differences were accompanied by differences in urinary metabolomes, cytokines, and patients’ disease profiles. The SLE-enriched genera, including Bacteroides, were positively correlated with several SLE-enriched metabolites, including olopatadine. The SLE-depleted genera, such as Pseudomonas, were negatively correlated to SLE-depleted cytokines, including IL-8. Alteration of the bladder microbiome was associated with disease profile. For example, the genera Megamonas and Phocaeicola were negatively correlated with serum complement C3, and Streptococcus was positively correlated with IgG.

Conclusions Our present study reveals associations between the bladder microbiome and the urinary metabolome, cytokines, and disease phenotypes. Our results could help identify biomarkers for SLE.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 14, 2022.
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The bladder microbiome, metabolome, cytokines, and phenotypes in patients with systemic lupus erythematosus
Fengping Liu, Jingjie Du, Qixiao Zhai, Jialin Hu, Aaron W. Miller, Tianli Ren, Yangkun Feng, Peng Jiang, Lei Hu, Jiayi Sheng, Chaoqun Gu, Ren Yan, Longxian Lv, Alan J. Wolfe, Ninghan Feng
bioRxiv 2022.01.13.476281; doi: https://doi.org/10.1101/2022.01.13.476281
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The bladder microbiome, metabolome, cytokines, and phenotypes in patients with systemic lupus erythematosus
Fengping Liu, Jingjie Du, Qixiao Zhai, Jialin Hu, Aaron W. Miller, Tianli Ren, Yangkun Feng, Peng Jiang, Lei Hu, Jiayi Sheng, Chaoqun Gu, Ren Yan, Longxian Lv, Alan J. Wolfe, Ninghan Feng
bioRxiv 2022.01.13.476281; doi: https://doi.org/10.1101/2022.01.13.476281

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