Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria

From BugSigDB
Reviewed Marked as Reviewed by Peace Sandy on 2024-1-23
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Shrode RL, Knobbe JE, Cady N, Yadav M, Hoang J, Cherwin C, Curry M, Garje R, Vikas P, Sugg S, Phadke S, Filardo E, Mangalam AK
Journal
Scientific reports
Year
2023
As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment.

Experiment 1


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-23

Curated date: 2023/10/03

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Peace Sandy

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
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
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,Breast cancer
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls (HC)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Breast cancer (BC)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
All BC patients eligible for this study were diagnosed with invasive BC of any stage, and recruited from the Breast Molecular Epidemiology Resource (BMER) of the Holden Comprehensive Cancer Center (HCCC)
Group 0 sample size Number of subjects in the control (unexposed) group
19
Group 1 sample size Number of subjects in the case (exposed) group
22
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Antibiotic use within four weeks of sample collection

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
Mann-Whitney (Wilcoxon)
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
Matched on Factors on which subjects have been matched on in a case-control study
body mass index, race, sex

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-23

Curated date: 2023/10/03

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Peace Sandy

Source: Figure 3

Description: Bacteria significantly increased in patients with breast cancer compared to healthy controls. (a–f) Based on the Wilcoxon test and the Benjamini–Hochberg procedure, 6 features were significantly higher in abundance in the breast cancer cohort compared to the healthy controls (p ≤ 0.05, q ≤ .15). Significance: * < 0.05 and ** < 0.01.

Abundance in Group 1: increased abundance in Breast cancer (BC)

NCBI Quality ControlLinks
Actinomyces
Blautia
Eggerthella
Faecalitalea
Intestinibacter bartlettii
Oscillospiraceae

Revision editor(s): ChiomaBlessing, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-23

Curated date: 2023/10/03

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Peace Sandy

Source: Figure 4

Description: Bacteria significantly decreased in patients with breast cancer compared to healthy controls. (a–h) Based on the Wilcoxon test and the Benjamini–Hochberg procedure, 8 features weresignificantly lower in abundance in the breast cancer cohort compared to the healthy controls (p ≤ 0.05, q ≤ 0.15). Significance: * < 0.05, ** < 0.01, and *** < 0.001.

Abundance in Group 1: decreased abundance in Breast cancer (BC)

NCBI Quality ControlLinks
Alistipes sp.
Faecalibacterium prausnitzii
Lachnoclostridium edouardi
Lachnospira pectinoschiza
Oscillibacter sp.
Parabacteroides merdae
uncultured Erysipelotrichaceae bacterium
uncultured Lachnospiraceae bacterium

Revision editor(s): ChiomaBlessing, Peace Sandy

Experiment 2


Needs review

Curated date: 2024/10/14

Curator: Som252

Revision editor(s): Som252

Differences from previous experiment shown

Subjects

Host species Species from which microbiome was sampled. Contact us to have more species added.
Macaca mulatta
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,breast
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Clinical laboratory measurement clinical laboratory techniques,Clinical laboratory measurement,clinical laboratory measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
health-control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Breast cancer
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
gut bacterial dysbiosis in breast cancer could lead to refned prevention and treatment
Group 0 sample size Number of subjects in the control (unexposed) group
24
Group 1 sample size Number of subjects in the case (exposed) group
23
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
4 weeks

Lab analysis

Statistical Analysis

Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.0001
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
3
Matched on Factors on which subjects have been matched on in a case-control study
sex, age

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/10/14

Curator: Som252

Revision editor(s): Som252

Source: Figure 3

Description: Bacteria signifcantly increased in patients with breast cancer compared to healthy controls. (a–f) Based on the Wilcoxon test and the Benjamini–Hochberg procedure, 6 features were signifcantly higher in abundance in the breast cancer cohort compared to the healthy controls (p≤0.05, q≤.15). Signifcance: *<0.05 and **<0.01.

Abundance in Group 1: increased abundance in Breast cancer

NCBI Quality ControlLinks
Bacteria
Acidobacteriota
Blastocatellia

Revision editor(s): Som252

Signature 2

Needs review

Curated date: 2024/10/14

Curator: Som252

Revision editor(s): Som252

Source: Figure 3

Description: Bacteria significantly increased in patients with breast cancer compared to healthy controls. (a–f) Based on the Wilcoxon test and the Benjamini–Hochberg procedure, 6 features were significantly higher in abundance in the breast cancer cohort compared to the healthy controls (p≤0.05, q≤.15). Significance: *<0.05 and **<0.01.

Abundance in Group 1: decreased abundance in Breast cancer

NCBI Quality ControlLinks
Bacteria
Acidobacteriota
Blastocatellia

Revision editor(s): Som252