Profiling the Urinary Microbiota in Male Patients With Bladder Cancer in China

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Reviewed Marked as Reviewed by Svetlana up on 2024-6-11
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Wu P, Zhang G, Zhao J, Chen J, Chen Y, Huang W, Zhong J, Zeng J
Journal
Frontiers in cellular and infection microbiology
Year
2018
Keywords:
extracellular matrix, inflammation, microbiota, urinary bladder neoplasms, urinary tract
Mounting evidence indicates that microbiome plays an important role in the development and progression of cancer. The dogma that urine in healthy individuals must be sterile has been overturned. Dysbiosis of the urinary microbiome has been revealed responsible for various urological disorders, including prostate cancer. The link between chronic inflammation, microbiome and solid tumors has been established for various neoplastic diseases. However, a detailed and comprehensive analysis of urinary microenvironment of bladder cancer has not been yet reported. We performed this study to characterize the potential urinary microbial community possibly associated with bladder cancer. Mid-stream urine was collected from 31 male patients with bladder cancer and 18 non-neoplastic controls. DNA was extracted from urine pellet samples and processed for high throughput 16S rRNA amplicon sequencing of the V4 region using Illumina MiSeq. Sequencing reads were filtered using QIIME and clustered using UPARSE. We observed increased bacterial richness (Observed Species, Chao 1 and Ace indexes; cancer vs. control; 120.0 vs. 56.0; 134.5 vs. 68.3; and 139.6 vs. 72.9, respectively), enrichment of some bacterial genera (e.g., Acinetobacter, Anaerococcus, and Sphingobacterium) and decrease of some bacterial genera (e.g., Serratia, Proteus, and Roseomonas) in cancer group when compared to non-cancer group. Significant difference in beta diversity was found between cancer and non-cancer group, among different risk level, but not among different tumor grade. Enrichment of Herbaspirillum, Porphyrobacter, and Bacteroides was observed in cancer patients with high risk of recurrence and progression, which means these genera maybe potential biomarkers for risk stratification. The PICRUSt showed that various functional pathways were enriched in cancer group, including Staphylococcus aureus infection, glycerolipid metabolism and retinol metabolism. To our knowledge, we performed the most comprehensive study to date to characterize the urinary microbiome associated with bladder cancer. A better understanding of the role of microbiome in the development and progression of bladder cancer could pave a new way for exploring new therapeutic options and biomarkers.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-6-11

Curated date: 2024/04/07

Curator: Ayibatari

Revision editor(s): Ayibatari, Scholastica

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Urine Urine,urine
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Bladder carcinoma bladder cancer,bladder carcinoma,cancer of bladder,cancer of the bladder,cancer of the urinary bladder,cancer of urinary bladder,carcinoma bladder,carcinoma of bladder,carcinoma of the bladder,carcinoma of the urinary bladder,carcinoma of urinary bladder,urinary bladder cancer,urinary bladder carcinoma,Bladder carcinoma
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non-neoplastic (controls)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Bladder cancer
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Male patients with bladder cancer
Group 0 sample size Number of subjects in the control (unexposed) group
18
Group 1 sample size Number of subjects in the case (exposed) group
31
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
1 month

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-11

Curated date: 2024/04/07

Curator: Ayibatari

Revision editor(s): Ayibatari, Scholastica

Source: Figure 4B

Description: Microbial taxa associated with bladder cancer (red) versus non-cancer group (green)

Abundance in Group 1: increased abundance in Bladder cancer

NCBI Quality ControlLinks
Acinetobacter
Acinetobacter baylyi
Anaerococcus
Atopostipes
Candidatus Limnoluna
Carnobacteriaceae
Geobacillus
Rickettsiales
Rothia
Rubrobacter
Rubrobacterales
Sphingobacteriaceae

Revision editor(s): Ayibatari, Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-11

Curated date: 2024/04/07

Curator: Ayibatari

Revision editor(s): Ayibatari, Scholastica

Source: Figure 4B

Description: Microbial taxa associated with bladder cancer (red) versus non-cancer group (green)

Abundance in Group 1: decreased abundance in Bladder cancer

NCBI Quality ControlLinks
Acetobacteraceae
Bacteroidia
Burkholderiaceae
Eubacterium xylanophilum
Proteus
Rhodospirillales
Roseomonas
Serratia
Ruminiclostridium-6Ruminiclostridium-6
Muribaculaceae

Revision editor(s): Ayibatari, Scholastica

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-6-11

Curated date: 2024/04/07

Curator: Ayibatari

Revision editor(s): Ayibatari, Scholastica

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Disease recurrence relapse,Disease recurrence,disease recurrence
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Lower risk of recurrence (LER)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Higher risk of recurrence (HER)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Male bladder cancer patients stratified into the higher risk of recurrence group (HER, recurrence score of EORTC ≥ 5) based on European Organization for Research and Treatment of Cancer (EORTC) scoring system
Group 0 sample size Number of subjects in the control (unexposed) group
16
Group 1 sample size Number of subjects in the case (exposed) group
10

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-11

Curated date: 2024/04/07

Curator: Ayibatari

Revision editor(s): Ayibatari, Scholastica

Source: Supplementary Figure 4B

Description: Microbial taxa associated with high risk of recurrence (HER, red) versus low risk of recurrence (LER, green)

Abundance in Group 1: increased abundance in Higher risk of recurrence (HER)

NCBI Quality ControlLinks
Aeromonadaceae
Aeromonadales
Aeromonas
Bacteroidaceae
Bacteroides
Campylobacteraceae
Campylobacterales
Chloroflexales
Chloroflexia
Dermabacteraceae
Epsilonproteobacteria
Erythrobacteraceae
Faecalibacterium
Gemella
Herbaspirillum
Nocardioidaceae
Porphyrobacter
Family_XIFamily_XI
Lachnospiraceae_ND3007_groupLachnospiraceae_ND3007_group

Revision editor(s): Ayibatari, Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-11

Curated date: 2024/04/07

Curator: Ayibatari

Revision editor(s): Ayibatari, Scholastica

Source: Supplementary Figure 4B

Description: Microbial taxa associated with high risk of recurrence (HER, red) versus low risk of recurrence (LER, green)

Abundance in Group 1: decreased abundance in Higher risk of recurrence (HER)

NCBI Quality ControlLinks
Escherichia/Shigella sp.

Revision editor(s): Ayibatari, Scholastica

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-6-11

Curated date: 2024/04/07

Curator: Ayibatari

Revision editor(s): Ayibatari, Scholastica

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Disease progression measurement Disease progression measurement,disease progression measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Lower risk of progression (LEP)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Higher risk of progression (HEP)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Male bladder cancer patients stratified into the higher risk of progression group (HEP, progression score of EORTC ≥ 7) based on European Organization for Research and Treatment of Cancer (EORTC) scoring system
Group 0 sample size Number of subjects in the control (unexposed) group
15
Group 1 sample size Number of subjects in the case (exposed) group
11

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-11

Curated date: 2024/04/07

Curator: Ayibatari

Revision editor(s): Ayibatari, Scholastica

Source: Supplementary Figure 5B

Description: Microbial taxa associated with high risk of progression (HEP, red) versus low risk of progression (LEP, green)

Abundance in Group 1: increased abundance in Higher risk of progression (HEP)

NCBI Quality ControlLinks
Bacteroidaceae
Bacteroides
Chloroflexales
Dermabacteraceae
Erythrobacteraceae
Marmoricola
Micrococcaceae
Nocardioidaceae
Porphyrobacter
Lachnospiraceae_ND3007_groupLachnospiraceae_ND3007_group

Revision editor(s): Ayibatari, Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-11

Curated date: 2024/04/07

Curator: Ayibatari

Revision editor(s): Ayibatari, Scholastica

Source: Supplementary Figure 5B

Description: Microbial taxa associated with high risk of progression (HEP, red) versus low risk of progression (LEP, green)

Abundance in Group 1: decreased abundance in Higher risk of progression (HEP)

NCBI Quality ControlLinks
Bacilli
Bacillota
Cyanobacteriota
Lactobacillales
uncultured Corynebacterium sp.

Revision editor(s): Ayibatari, Scholastica