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Chun-Ying Wu
Institute of Biomedical Informatics, Institute of Clinical Medicine, Institute of Public Health and Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5053-1801
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Background: Patients with end-stage renal disease (ESRD) have extremely high risks of mortality and morbidity, as well as altered gut microbiota and impaired intestinal barrier function. The translocation of gut-derived molecules in ESRD contributes to systemic complications. In this study, we evaluated the gut microbiome difference in ESRD patients compared to age- and gender-matched subjects without kidney disease in discovery and validation cohorts.
Results: Compared to controls with normal renal function, an increased α-diversity and distinct β-diversity were found in ESRD subjects. The increase in α-diversity was correlated with protein-bound uremic toxins, particularly hippuric acid. A higher microbial dysbiosis index (MDI) was found in ESRD patients with the following enriched genera: Facealibacterium, Ruminococcus, Fusobacterium, Dorea, Anaerovorax, Sarcina, Akkemansia, Streptococcus, and Dysgonomonas. MDI at the genus level demonstrated highly differentiated accuracies between ESRD and control subjects in the discovery cohort (area under the curve [AUC] of 81.9%) and between ESRD and control subjects in the validation cohort (AUC of 83.2%). On functional enrichment analysis with gut metabolic modules, ESRD subjects presented with increased saccharide and amino acid metabolism when compared with matched controls.
Conclusions: An enriched but dysbiotic gut microbiota was presented in ESRD patients, in which the bacteria that were present increase amino acid metabolism linked to the production of protein-bound uremic toxins.
Keywords
microbiota, dysbiosis, end-stage renal disease, protein-bound uremic toxins, hippuric acid
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This is a list of supplementary files associated with this preprint. Click to download.
- Allsupplementaryfiguresandtables20200919.docx
Supplementary information Figure S1. ESRD patients had a different β diversity (Bray-Curtis distance metrics) compared to the general population at different taxonomy levels in the discovery cohort and validation cohort Figure S2. Fecal microbiota composition profiles and the top microbial relative abundance difference between ESRD and control subjects at different taxonomy levels in the discovery cohort. The selected different taxonomy was presented. (A) Phylum level (B) Class level (C) Order level (D) Family level (E) Genus level (F) Species level Figure S3. LEfSe analysis with linear discriminant analysis (LDA) scores representing microbial differences between groups at different taxonomy levels in the discovery cohort. Green indicates taxa enriched in the ESRD group and red indicates taxa enriched in the control group Figure S4. The microbial dysbiosis index (MDI) between ESRD patients and control subjects across different taxonomy levels. The differentiate accuracy of MDI between ESRD patients and control subjects across different taxonomy levels in the discovery cohort and confirmed the differentiate accuracy of MDI in the validation cohort Figure S5. Enrichment analysis was performed to identify gene functions of differential abundances in gut microbiota between ESRD patients and control subjects. Functional classification of the predicted metagenome content of the microbiota of ESRD using clusters of Orthologous Groups (COG) in the discovery cohort and validation cohort. Significance was considered for an adjusted P<0.05 Figure S6. Enrichment analysis was performed to identify gene functions of differential abundances in gut microbiota between ESRD patients and control subjects. Functional classification of the predicted metagenome content of the microbiota of ESRD using the Kyoto Encyclopedia of Genes and Genome (KEGG) in the discovery cohort and validation cohort. Significance was considered for an adjusted P<0.05 Figure S7. Normalized protein catabolic rate (nPCR) and alpha diversity relationship in the discovery cohort. The alpha diversity difference was evaluated between nPCR >1.2 and ≦1.2 g/kg per day Table S1. The specifically increased taxa in ESRD patients using LEfSe analysis Table S2. The full results of GMM enrichment analysis. The GMM enrichment analysis was performed in discovery and validation cohorts contrasting to their respective matched healthy groups. Significance (P value) was tested by a two-tailed Wilcoxon test and adjusted by false-discovery rate correction
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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
Chun-Ying Wu
Institute of Biomedical Informatics, Institute of Clinical Medicine, Institute of Public Health and Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5053-1801
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CURRENT STATUS: Posted
Version 1
Posted 30 Sep, 2020
No community comments so far
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Comments: 0
PDF Downloads: ...
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Subject Areas
General Microbiology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Patients with end-stage renal disease (ESRD) have extremely high risks of mortality and morbidity, as well as altered gut microbiota and impaired intestinal barrier function. The translocation of gut-derived molecules in ESRD contributes to systemic complications. In this study, we evaluated the gut microbiome difference in ESRD patients compared to age- and gender-matched subjects without kidney disease in discovery and validation cohorts.
Results: Compared to controls with normal renal function, an increased α-diversity and distinct β-diversity were found in ESRD subjects. The increase in α-diversity was correlated with protein-bound uremic toxins, particularly hippuric acid. A higher microbial dysbiosis index (MDI) was found in ESRD patients with the following enriched genera: Facealibacterium, Ruminococcus, Fusobacterium, Dorea, Anaerovorax, Sarcina, Akkemansia, Streptococcus, and Dysgonomonas. MDI at the genus level demonstrated highly differentiated accuracies between ESRD and control subjects in the discovery cohort (area under the curve [AUC] of 81.9%) and between ESRD and control subjects in the validation cohort (AUC of 83.2%). On functional enrichment analysis with gut metabolic modules, ESRD subjects presented with increased saccharide and amino acid metabolism when compared with matched controls.
Conclusions: An enriched but dysbiotic gut microbiota was presented in ESRD patients, in which the bacteria that were present increase amino acid metabolism linked to the production of protein-bound uremic toxins.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- Allsupplementaryfiguresandtables20200919.docx
Supplementary information Figure S1. ESRD patients had a different β diversity (Bray-Curtis distance metrics) compared to the general population at different taxonomy levels in the discovery cohort and validation cohort Figure S2. Fecal microbiota composition profiles and the top microbial relative abundance difference between ESRD and control subjects at different taxonomy levels in the discovery cohort. The selected different taxonomy was presented. (A) Phylum level (B) Class level (C) Order level (D) Family level (E) Genus level (F) Species level Figure S3. LEfSe analysis with linear discriminant analysis (LDA) scores representing microbial differences between groups at different taxonomy levels in the discovery cohort. Green indicates taxa enriched in the ESRD group and red indicates taxa enriched in the control group Figure S4. The microbial dysbiosis index (MDI) between ESRD patients and control subjects across different taxonomy levels. The differentiate accuracy of MDI between ESRD patients and control subjects across different taxonomy levels in the discovery cohort and confirmed the differentiate accuracy of MDI in the validation cohort Figure S5. Enrichment analysis was performed to identify gene functions of differential abundances in gut microbiota between ESRD patients and control subjects. Functional classification of the predicted metagenome content of the microbiota of ESRD using clusters of Orthologous Groups (COG) in the discovery cohort and validation cohort. Significance was considered for an adjusted P<0.05 Figure S6. Enrichment analysis was performed to identify gene functions of differential abundances in gut microbiota between ESRD patients and control subjects. Functional classification of the predicted metagenome content of the microbiota of ESRD using the Kyoto Encyclopedia of Genes and Genome (KEGG) in the discovery cohort and validation cohort. Significance was considered for an adjusted P<0.05 Figure S7. Normalized protein catabolic rate (nPCR) and alpha diversity relationship in the discovery cohort. The alpha diversity difference was evaluated between nPCR >1.2 and ≦1.2 g/kg per day Table S1. The specifically increased taxa in ESRD patients using LEfSe analysis Table S2. The full results of GMM enrichment analysis. The GMM enrichment analysis was performed in discovery and validation cohorts contrasting to their respective matched healthy groups. Significance (P value) was tested by a two-tailed Wilcoxon test and adjusted by false-discovery rate correction
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