CANCER AND THE MICROBIOME: A MIXED-METHODS COHORT STUDY ON HOW GUT BACTERIA INFLUENCE TUMOUR GROWTH AND CHEMOTHERAPY RESISTANCE
Main Article Content
Keywords
gut microbiota, chemotherapy resistance, microbial diversity, cancer survival, Fusobacterium nucleatum
Abstract
Background: The gut microbiota has emerged as a modifiable determinant of cancer therapy outcomes. This study investigates the relationship between gut microbiota diversity and composition with chemotherapy response, survival, and adverse events in patients with solid tumours.
Methods: In this prospective cohort study conducted over three years, 114 patients with histologically confirmed solid malignancies were enrolled. Baseline stool samples were collected for 16S rRNA sequencing. Clinical outcomes including response to chemotherapy (per RECIST), overall survival, and treatment-related toxicity were tracked. Statistical analysis included multivariate regression and Kaplan–Meier survival analysis.
Results: Patients with higher baseline Shannon diversity index had significantly better response rates (OR = 2.34, p = 0.001), longer overall survival (HR = 0.62, p = 0.002), and fewer grade ≥2 adverse events. Responders showed enrichment of Faecalibacterium prausnitzii and Bifidobacterium adolescentis, while non-responders were characterized by elevated Fusobacterium nucleatum, which independently predicted poor outcomes. Microbiota diversity remained an independent predictor after adjusting for tumour type and stage.
Conclusion: Gut microbial diversity and composition are significant predictors of chemotherapy efficacy and toxicity. These findings support integrating microbiome profiling into personalized cancer care and justify further research into microbiome-targeted therapeutic strategies.
References
2. Garajová, I., Balsano, R., Wang, H., & Leonardi, F. (2021). The role of the microbiome in drug resistance in gastrointestinal cancers. Expert Review of Anticancer Therapy, 21(2), 151–161. https://doi.org/10.1080/14737140.2021.1844007
3. Mendes, I., & Vale, N. (2023). How can the microbiome induce carcinogenesis and modulate drug resistance in cancer therapy? International Journal of Molecular Sciences, 24(14), 11855. https://doi.org/10.3390/ijms241411855
4. Pouncey, A. L., Scott, A. J., & Alexander, J. L. (2018). Gut microbiota, chemotherapy and the host: the influence of the gut microbiota on cancer treatment. Cancer Drug Resistance, 12, 868. https://pmc.ncbi.nlm.nih.gov/articles/PMC6145523/
5. Pandey, K., & Umar, S. (2021). Microbiome in drug resistance to colon cancer. Translational Oncology, 14(11), 101173. https://www.sciencedirect.com/science/article/pii/S2468867321000973
6. Kenneth, M. J., Wu, C. C., Fang, C. Y., Hsu, T. K., & Lin, I. C. (2025). Exploring the impact of chemotherapy on the emergence of antibiotic resistance in the gut microbiota of colorectal cancer patients. Antibiotics, 14(3), 264. https://doi.org/10.3390/antibiotics14030264
7. Shui, L., Yang, X., Li, J., Yi, C., Sun, Q., & Zhu, H. (2020). Gut microbiome as a potential factor for modulating resistance to cancer immunotherapy. Frontiers in Immunology, 10, 2989. https://doi.org/10.3389/fimmu.2019.02989
8. Yin, B., Wang, X., Yuan, F., Li, Y., & Lu, P. (2022). Research progress on the effect of gut and tumor microbiota on antitumor efficacy and adverse effects of chemotherapy drugs. Frontiers in Microbiology, 13, 899111. https://doi.org/10.3389/fmicb.2022.899111
9. Xiaofeng, N., Jian, C., Jingjing, W., Zhanbo, Q., Yifei, S., Jing, Z., & Shuwen, H. (2023). Correlation of gut microbiota with leukopenia after chemotherapy in patients with colorectal cancer. BMC Microbiology, 23(1), 349. https://doi.org/10.1186/s12866-023-03072-z
10. Li, Y., Dong, B., Wu, W., Wang, J., Jin, H., Chen, K., ... & Yao, Y. (2022). Metagenomic analyses reveal distinct gut microbiota signature for predicting the neoadjuvant chemotherapy responsiveness in breast cancer patients. Frontiers in Oncology, 12, 865121. https://doi.org/10.3389/fonc.2022.865121
11. Aarnoutse, R., Ziemons, J., Hillege, L. E., de Vos-Geelen, J., de Boer, M., Bisschop, S. M., ... & Smidt, M. L. (2022). Changes in intestinal microbiota in postmenopausal oestrogen receptor-positive breast cancer patients treated with (neo)adjuvant chemotherapy. NPJ Breast Cancer, 8(1), 89. https://doi.org/10.1038/s41523-022-00434-8
12. Gong, T. T., He, X. H., Gao, S., & Wu, Q. J. (2021). Application of machine learning in prediction of chemotherapy resistance of ovarian cancer based on gut microbiota. Journal of Cancer, 12(10), 2877–2886. https://doi.org/10.7150/jca.55189
13. El Bairi, K., Jabi, R., Trapani, D., Boutallaka, H., Ouled Amar Bencheikh, B., Bouziane, M., ... & Maleb, A. (2020). Can the microbiota predict response to systemic cancer therapy, surgical outcomes, and survival? The answer is in the gut. Expert Review of Clinical Pharmacology, 13(4), 403–421. https://doi.org/10.1080/17512433.2020.1744782
14. Nakamoto, S., Kajiwara, Y., Taniguchi, K., Hida, A. I., Miyoshi, Y., Kin, T., ... & Toyooka, S. (2024). Baseline gut microbiota as a predictive marker for the efficacy of neoadjuvant chemotherapy in patients with early breast cancer: A multicenter prospective cohort study in the Setouchi Breast Project-14. Breast Cancer Research and Treatment, 208(1), 67–77. https://doi.org/10.1007/s10549-023-07076-y
15. Zuraik, A. A., Daboul, Y., Awama, M. A., Yazigi, H., Kayasseh, M. D. A., & Georges, M. (2024). Effect of chemotherapy on Fusobacterium nucleatum abundance in colorectal cancer patients: A study on relapsing patients. Indian Journal of Microbiology, 64(4), 1938–1950. https://doi.org/10.1007/s12088-024-01124-8
16. Leigh, S. J., Lynch, C. M., Bird, B. R. H., Griffin, B. T., Cryan, J. F., & Clarke, G. (2022). Gut microbiota–drug interactions in cancer pharmacotherapies: Implications for efficacy and adverse effects. Expert Opinion on Drug Metabolism & Toxicology, 18(1), 5–26. https://doi.org/10.1080/17425255.2022.2022145
17. Mafe, A. N., & Büsselberg, D. (2025). Microbiome integrity enhances the efficacy and safety of anticancer drug. Biomedicines, 13(2), 422. https://doi.org/10.3390/biomedicines13020422
18. Kim, K., Lee, M., Shin, Y., Lee, Y., & Kim, T. J. (2025). Optimizing cancer treatment through gut microbiome modulation. Cancers, 17(7), 1252. https://doi.org/10.3390/cancers17071252
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Sree Ramya Dangeti
Assistant Professor, Department of pathology GSL Medical College and Hospital
Dr Neelima Pantagada
Associate Professor, Department of Microbiology GSL Medical College and General Hospital
Sruthi Nannapaneni
Professor, Department of Pathology GSL Medical College Lakshmipuram, Rajamahendravanam