Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Scientific Reports
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. scientific reports
  3. articles
  4. article
Differences in composition and diversity of the gut microbiota of post-menopausal breast cancer patients
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 09 April 2026

Differences in composition and diversity of the gut microbiota of post-menopausal breast cancer patients

  • Nadia Kabbej1,
  • John D. Sommerville1,
  • Raad Z. Gharaibeh1,2,
  • Khloe Dang1,
  • Erika Atencio1,
  • Erinn Rosenkrantz1,
  • Dominique Day1,
  • Frederick Ashby1,
  • Taqwa Naas1,
  • Josee Gauthier1,
  • Rachel Newsome1,
  • Christian Jobin1,
  • Amira Quevedo1,
  • Mansour MohamadZadeh3 &
  • …
  • Coy D. Heldermon1 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Breast cancer
  • Cancer
  • Oncology

Abstract

The gut microbiota colonizes the intestinal tract with essential roles in immune function, gut epithelial integrity, and metabolic signaling. To investigate the relationship between microbiota composition and breast cancer development, stool samples were collected from 27 treatment naïve post-menopausal breast cancer patients of varying hormone receptor statuses and 25 post-menopausal participants without breast cancer who served as controls. Samples from breast cancer patients and controls were compared for significant differences (p<0.05) in alpha and beta diversity. Significant differences in alpha diversity were observed between all breast cancer types compared to controls (padj=0.042), and between ER+Her2- breast cancer compared to controls (padj=0.006). Using principal coordinate analyses (PCA), significant differences in beta diversity were identified between all breast cancer types compared to controls (padj=0.048), and ER+Her2- breast cancer compared to controls (padj=0.036). Further analyses identified key microbiota genera of microbiota related to breast cancer development and progression. Notably, Akkermansia, a genus associated with gut barrier dysfunction, was reduced in ER+Her2- patients. Overall, this study reports on alterations in microbiota composition in stool samples from untreated postmenopausal breast cancer patients compared to control subjects. The data obtained could provide important insights into the association between altered microbiota and breast cancer progression and guide future patient screening and prevention efforts.

Data availability

Sequencing reads have been deposited in the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) under project ID: PRJNA1260020.

References

  1. Cancer Facts & Figs. 2025. (1930).

  2. Eslami-S, Z., Majidzadeh-A, K., Halvaei, S., Babapirali, F. & Esmaeili, R. Microbiome and Breast Cancer: New Role for an Ancient Population. Front Oncol 10:120, (2020) doi: 10.3389/fonc.2020.00120

  3. Álvarez-Mercado, A. I., del Valle Cano, A., Fernández, M. F. & Fontana, L. Gut Microbiota and Breast Cancer: The Dual Role of Microbes. Cancers 15, 443 (2023).

    Google Scholar 

  4. Baker, J. M., Al-Nakkash, L., Herbst-Kralovetz, M. & M Estrogen–gut microbiome axis: Physiological and clinical implications. Maturitas 103, 45–53 (2017).

    Google Scholar 

  5. Mikó, E. et al. Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness. Biochim. Biophys. Acta Bioenerg. 1859, 958–974 (2018).

    Google Scholar 

  6. Kovács, T. et al. Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors. Sci. Rep. 9, 1300 (2019).

    Google Scholar 

  7. Goedert, J. J. et al. Investigation of the Association Between the Fecal Microbiota and Breast Cancer in Postmenopausal Women: a Population-Based Case-Control Pilot Study. JNCI J. Natl. Cancer Inst. 107, djv147 (2015).

    Google Scholar 

  8. Johnson, J. S. et al. Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis. Nat. Commun. 10, 5029 (2019).

    Google Scholar 

  9. Farhadfar, N. et al. Gut Microbiota Dysbiosis Associated with Persistent Fatigue in Hematopoietic Cell Transplantation Survivors. Transpl. Cell. Ther. 27, 498e1–498e8 (2021).

    Google Scholar 

  10. Tomkovich, S. et al. Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis. Cancer Res. 77, 2620–2632 (2017).

    Google Scholar 

  11. Callahan, B. J. et al. DADA2: High-resolution sample inference from Illumina amplicon data. Nat. Methods. 13, 581–583 (2016).

    Google Scholar 

  12. McMurdie, P. J. & Holmes, S. phyloseq: An R Package for Reproducible Interactive Analysis and Graphics of Microbiome Census Data. PLOS ONE. 8, e61217 (2013).

    Google Scholar 

  13. McCafferty, J. et al. Stochastic changes over time and not founder effects drive cage effects in microbial community assembly in a mouse model. ISME J. 7, 2116–2125 (2013).

    Google Scholar 

  14. Oksanen, J. et al. vegan: Community Ecology Package. (2025).

  15. Zhou, H., He, K., Chen, J. & Zhang, X. LinDA: linear models for differential abundance analysis of microbiome compositional data. Genome Biol. 23, 95 (2022).

    Google Scholar 

  16. Benjamini, Y. & Hochberg, Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J. R Stat. Soc. Ser. B Methodol. 57, 289–300 (1995).

    Google Scholar 

  17. Bobin-Dubigeon, C. et al. Faecal Microbiota Composition Varies between Patients with Breast Cancer and Healthy Women: A Comparative Case-Control Study. Nutrients 13, 2705 (2021).

    Google Scholar 

  18. Ullern, A. et al. Gut microbiota diversity is prognostic and associated with benefit from chemo-immunotherapy in metastatic triple-negative breast cancer. Mol. Oncol. https://doi.org/10.1002/1878-0261.13760 (2024).

    Google Scholar 

  19. Otto-Dobos, L. D. et al. Baseline gut microbiome alpha diversity predicts chemotherapy-induced gastrointestinal symptoms in patients with breast cancer. NPJ Breast Cancer. 10, 99 (2024).

    Google Scholar 

  20. Fernandez, E., Wargo, J. A. & Helmink, B. A. The Microbiome and Cancer: A Translational Science Review. JAMA 333, 2188–2196 (2025).

    Google Scholar 

  21. Rodrigues, V. F. et al. Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes. Front. Immunol. 13, 934695 (2022).

    Google Scholar 

  22. Ghotaslou, R. et al. The metabolic, protective, and immune functions of Akkermansia muciniphila. Microbiol. Res. 266, 127245 (2023).

    Google Scholar 

  23. Frugé, A. D. et al. Fecal Akkermansia muciniphila Is Associated with Body Composition and Microbiota Diversity in Overweight and Obese Women with Breast Cancer Participating in a Presurgical Weight Loss Trial. J. Acad. Nutr. Diet. 120, 650–659 (2020).

    Google Scholar 

  24. Tzenios, N., Tazanios, M. E. & Chahine, M. The impact of BMI on breast cancer – an updated systematic review and meta-analysis. Med. (Baltim). 103, e36831 (2023).

    Google Scholar 

  25. Zhu, L. B., Zhang, Y. C., Huang, H. H. & Lin, J. Prospects for clinical applications of butyrate-producing bacteria. World J. Clin. Pediatr. 10, 84–92 (2021).

    Google Scholar 

  26. Singh, V. et al. Butyrate producers, The Sentinel of Gut: Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics. Front Microbiol 13:1103836, (2023) doi: 10.3389/fmicb.2022.1103836.

  27. Hodgkinson, K. et al. Butyrate’s role in human health and the current progress towards its clinical application to treat gastrointestinal disease. Clin. Nutr. 42, 61–75 (2023).

    Google Scholar 

  28. Chen, J., Zhao, K. N. & Vitetta, L. Effects of Intestinal Microbial–Elaborated Butyrate on Oncogenic Signaling Pathways. Nutrients 11, 1026 (2019).

    Google Scholar 

  29. Seethaler, B. et al. Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: data from the randomized controlled LIBRE trial. Am. J. Clin. Nutr. 116, 928–942 (2022).

    Google Scholar 

  30. Kaźmierczak-Siedlecka, K., Marano, L., Merola, E., Roviello, F. & Połom, K. Sodium butyrate in both prevention and supportive treatment of colorectal cancer. Front Cell. Infect. Microbiol 12:1023806, (2022) doi: 10.3389/fcimb.2022.1023806.

  31. Lee, S. Y. et al. Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer. Gut Microbes. 16, 2300846 (2024).

    Google Scholar 

  32. Zhang, L., Huang, S. & Yuan, Y. Butyrate inhibits the malignant biological behaviors of breast cancer cells by facilitating cuproptosis-associated gene expression. J. Cancer Res. Clin. Oncol. 150, 287 (2024).

    Google Scholar 

  33. Devoy, C., Flores Bueso, Y. & Tangney, M. Understanding and harnessing triple-negative breast cancer-related microbiota in oncology. Front Oncol 12:1020121, (2022) doi: 10.3389/fonc.2022.1020121.

  34. Thirunavukkarasan, M. et al. Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells. PLOS ONE. 12, e0186334 (2017).

    Google Scholar 

  35. Kang, X., Lau, H. C. H. & Yu, J. Modulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy. Cell. Rep. Med. 5, 101478 (2024).

    Google Scholar 

Download references

Acknowledgments

Funding for these studies was provided by University of Florida Health Cancer Center Cancer Therapeutics and Host Response Pilot Grant (MMZ and CDH), UF Interdisciplinary Center for Biotechnology Research Pilot Grant (RZG and CDH), Robert A. Wynn Diversity in Clinical Trials Award – Bristol Myers Squibb Foundation (AQ).

Author information

Authors and Affiliations

  1. University of Florida College of Medicine, Gainesville, FL, USA

    Nadia Kabbej, John D. Sommerville, Raad Z. Gharaibeh, Khloe Dang, Erika Atencio, Erinn Rosenkrantz, Dominique Day, Frederick Ashby, Taqwa Naas, Josee Gauthier, Rachel Newsome, Christian Jobin, Amira Quevedo & Coy D. Heldermon

  2. Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA

    Raad Z. Gharaibeh

  3. Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health-San Antonio, San Antonio, TX, USA

    Mansour MohamadZadeh

Authors
  1. Nadia Kabbej
    View author publications

    Search author on:PubMed Google Scholar

  2. John D. Sommerville
    View author publications

    Search author on:PubMed Google Scholar

  3. Raad Z. Gharaibeh
    View author publications

    Search author on:PubMed Google Scholar

  4. Khloe Dang
    View author publications

    Search author on:PubMed Google Scholar

  5. Erika Atencio
    View author publications

    Search author on:PubMed Google Scholar

  6. Erinn Rosenkrantz
    View author publications

    Search author on:PubMed Google Scholar

  7. Dominique Day
    View author publications

    Search author on:PubMed Google Scholar

  8. Frederick Ashby
    View author publications

    Search author on:PubMed Google Scholar

  9. Taqwa Naas
    View author publications

    Search author on:PubMed Google Scholar

  10. Josee Gauthier
    View author publications

    Search author on:PubMed Google Scholar

  11. Rachel Newsome
    View author publications

    Search author on:PubMed Google Scholar

  12. Christian Jobin
    View author publications

    Search author on:PubMed Google Scholar

  13. Amira Quevedo
    View author publications

    Search author on:PubMed Google Scholar

  14. Mansour MohamadZadeh
    View author publications

    Search author on:PubMed Google Scholar

  15. Coy D. Heldermon
    View author publications

    Search author on:PubMed Google Scholar

Contributions

NK and JDS wrote the primary manuscript, KD, EA, ER, DD, NK, and TN consented patients, FA, JG, and RN processed samples for sequencing, CJ provided material support, RZG performed sequencing analysis and manuscript editing, AQ provided material support, MMZ provided material support and conceptualized the study design, CDH provided material support, conceptualized and operationalized the study, consented patients, and edited the manuscript.

Corresponding author

Correspondence to Coy D. Heldermon.

Ethics declarations

Competing interests

The authors declare no competing interests. CDH consults for numerous legal and pharmaceutical interests none of which are conflicts of interest with the current study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1 (download DOCX )

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kabbej, N., Sommerville, J.D., Gharaibeh, R.Z. et al. Differences in composition and diversity of the gut microbiota of post-menopausal breast cancer patients. Sci Rep (2026). https://doi.org/10.1038/s41598-026-47558-8

Download citation

  • Received: 05 June 2025

  • Accepted: 01 April 2026

  • Published: 09 April 2026

  • DOI: https://doi.org/10.1038/s41598-026-47558-8

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Download PDF

Advertisement

Explore content

  • Research articles
  • News & Comment
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • About Scientific Reports
  • Contact
  • Journal policies
  • Guide to referees
  • Calls for Papers
  • Editor's Choice
  • Journal highlights
  • Open Access Fees and Funding

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Scientific Reports (Sci Rep)

ISSN 2045-2322 (online)

nature.com footer links

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer