Composition and Functional Potential of the Human Mammary Microbiota Prior to and Following Breast Tumor Diagnosis
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Hoskinson C, Zheng K, Gabel J, Kump A, German R, Podicheti R, Marino N, Stiemsma LT
Journal
mSystems
Year
2022
Keywords:
16S, breast cancer, breast tissue, functional metagenome, microbiome, transcriptome
Microbiota studies have reported changes in the microbial composition of the breast upon cancer development. However, results are inconsistent and limited to the later phases of cancer development (after diagnosis). We analyzed and compared the resident bacterial taxa of histologically normal breast tissue (healthy, H, n = 49) with those of tissues donated prior to (prediagnostic, PD, n = 15) and after (adjacent normal, AN, n = 49, and tumor, T, n = 46) breast cancer diagnosis (n total = 159). DNA was isolated from tissue samples and submitted for Illumina MiSeq paired-end sequencing of the V3-V4 region of the 16S gene. To infer bacterial function in breast cancer, we predicted the functional bacteriome from the 16S sequencing data using PICRUSt2. Bacterial compositional analysis revealed an intermediary taxonomic signature in the PD tissue relative to that of the H tissue, represented by shifts in Bacillaceae, Burkholderiaceae, Corynebacteriaceae, Streptococcaceae, and Staphylococcaceae. This compositional signature was enhanced in the AN and T tissues. We also identified significant metabolic reprogramming of the microbiota of the PD, AN, and T tissue compared with the H tissue. Further, preliminary correlation analysis between host transcriptome profiling and microbial taxa and genes in H and PD tissues identified altered associations between the human host and mammary microbiota in PD tissue compared with H tissue. These findings suggest that compositional shifts in bacterial abundance and metabolic reprogramming of the breast tissue microbiota are early events in breast cancer development that are potentially linked with cancer susceptibility. IMPORTANCE The goal of this study was to determine the role of resident breast tissue bacteria in breast cancer development. We analyzed breast tissue bacteria in healthy breast tissue and breast tissue donated prior to (precancerous) and after (postcancerous) breast cancer diagnosis. Compared to healthy tissue, the precancerous and postcancerous breast tissues demonstrated differences in the amounts of breast tissue bacteria. In addition, breast tissue bacteria exhibit different functions in pre-cancerous and post-cancerous breast tissues relative to healthy tissue. These differences in function are further emphasized by altered associations of the breast tissue bacteria with gene expression in the human host prior to cancer development. Collectively, these analyses identified shifts in bacterial abundance and metabolic function (dysbiosis) prior to breast tumor diagnosis. This dysbiosis may serve as a therapeutic target in breast cancer prevention.
Experiment 1
Needs review
Subjects
- Location of subjects
- United States of America
- 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
- Breast Mamma,Mammary part of chest,Mammary region,Breast
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- breast cancer breast cancer,breast tumor,cancer of breast,malignant breast neoplasm,malignant breast tumor,malignant neoplasm of breast,malignant neoplasm of the breast,malignant tumor of breast,malignant tumor of the breast,mammary cancer,mammary neoplasm,mammary tumor,primary breast cancer
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Health (H)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Prediagnostic (PD)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Samples donated prior to breast cancer diagnosis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 49
- Group 1 sample size Number of subjects in the case (exposed) group
- 15
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-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
- increased
- Chao1 Abundance-based estimator of species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Needs review
Source: Figure 3b
Description: Differentially abundant taxa in human mammary tissue subtypes. LEfSe analysis for H versus PD
Abundance in Group 1: increased abundance in Prediagnostic (PD)
| NCBI | Quality Control | Links |
|---|---|---|
| Caldimonas | ||
| Fusobacterium | ||
| Pantoea | ||
| Romboutsia | ||
| Sphingomonas | ||
| Staphylococcus | ||
| Streptococcus sp. |
Revision editor(s): OdigiriGreat
Signature 2
Needs review
Source: Figure 3b
Description: Differentially abundant taxa in human mammary tissue subtypes. LEfSe analysis for H versus PD
Abundance in Group 1: decreased abundance in Prediagnostic (PD)
| NCBI | Quality Control | Links |
|---|---|---|
| Corynebacterium |
Revision editor(s): OdigiriGreat
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Adjacent normal (AN)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- samples donated after breast cancer diagnosis (AN)
- Group 1 sample size Number of subjects in the case (exposed) group
- 49
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Needs review
Source: Figure 3c
Description: Differentially abundant taxa in human mammary tissue subtypes. LEfSe analysis for H versus AN
Abundance in Group 1: increased abundance in Adjacent normal (AN)
Revision editor(s): OdigiriGreat
Signature 2
Needs review
Source: Figure 3c
Description: Differentially abundant taxa in human mammary tissue subtypes. LEfSe analysis for H versus AN
Abundance in Group 1: decreased abundance in Adjacent normal (AN)
Revision editor(s): OdigiriGreat
Experiment 3
Needs review
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Tumor (T)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Samples donated after breast cancer diagnosis (tumor)
- Group 1 sample size Number of subjects in the case (exposed) group
- 46
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Needs review
Source: Figure 3d
Description: Differentially abundant taxa in human mammary tissue subtypes. LEfSe analysis for H versus T
Abundance in Group 1: increased abundance in Tumor (T)
| NCBI | Quality Control | Links |
|---|---|---|
| Anaerococcus | ||
| Pseudogracilibacillus | ||
| Rhodococcus | ||
| Enterococcus sp. | ||
| Pseudomonas sp. | ||
| Herbaspirillum sp. | ||
| Staphylococcus sp. |
Revision editor(s): OdigiriGreat
Signature 2
Needs review
Source: Figure 3d
Description: Differentially abundant taxa in human mammary tissue subtypes. LEfSe analysis for H versus T
Abundance in Group 1: decreased abundance in Tumor (T)
Revision editor(s): OdigiriGreat
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