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

Study information

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

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

36631533

DOI Digital object identifier for electronic documents.

10.1038/s41598-023-27436-3

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

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

Curated date: 2023/10/03

Curator: ChiomaBlessing

Revision editor(s): WikiWorks, Peace Sandy, ChiomaBlessing, KateRasheed

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): 1 month

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

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Curated date: 2023/10/03

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Peace Sandy, WikiWorks

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)

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Actinomyces
Blautia
Eggerthella
Faecalitalea
Intestinibacter bartlettii
Oscillospiraceae

Revision editor(s): ChiomaBlessing, Peace Sandy, WikiWorks

Signature 2

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Curated date: 2023/10/03

Curator: ChiomaBlessing

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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)

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

Revision editor(s): ChiomaBlessing, Peace Sandy, WikiWorks

Experiment 2

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Curated date: 2024/10/14

Curator: Som252

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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

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: age, 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

Richness Number of species: unchanged

Signature 1

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Curated date: 2024/10/14

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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 Control	Links
Bacteria
Acidobacteriota
Blastocatellia

Revision editor(s): Som252, WikiWorks

Signature 2

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/10/14

Curator: Som252

Revision editor(s): Som252, WikiWorks

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 Control	Links
Bacteria
Acidobacteriota
Blastocatellia

Revision editor(s): Som252, WikiWorks