Potential Risk of Tamoxifen: Gut Microbiota and Inflammation in Mice with Breast Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Jul 20

PMID 37469407

Authors

Hailong Li

Xiufei Gao

Yian Chen

Mengqian Wang

Chuchu Xu

Qinghong Yu

Ying Jin

Jiaqing Song

Qi Zhu

Affiliations

Soon will be listed here.

Abstract

Objective: Tamoxifen is an effective anti-tumor medicine, but evidence has been provided on tamoxifen-related inflammation as well as its impact on gut microbiota. In this study, we aimed to investigate tamoxifen-induced gut microbiota and inflammation alteration.

Methods: We established a BC xenograft mouse model using the MCF-7 cell line. 16S rRNA gene sequencing was used to investigate gut microbiota. qRT-PCR, western blotting, and cytometric bead array were used to investigate inflammation-related biomarkers. Various bioinformatic approaches were used to analyze the data.

Results: Significant differences in gut microbial composition, characteristic taxa, and microbiome phenotype prediction were observed between control, model, and tamoxifen-treated mice. Furthermore, protein expression of IL-6 and TLR5 was up-regulated in tamoxifen-treated mice, while the mRNA of Tlr5 and Il-6, as well as protein expression of IL-6 and TLR5 in the model group, were down-regulated in the colon. The concentration of IFN-γ, IL-6, and IL12P70 in serum was up-regulated in tamoxifen-treated mice. Moreover, correlation-based clustering analysis demonstrated that inflammation-negatively correlated taxa, including and , were enriched in the model group, while inflammation-positively correlated taxa, including and , were enriched in the tamoxifen-treated group. Finally, colon histologic damage was observed in tamoxifen-treated mice.

Conclusion: Tamoxifen treatment significantly altered gut microbiota and increased inflammation in the breast cancer xenograft mice model. This may be related to tamoxifen-induced intestinal epithelial barrier damage and TLR5 up-regulation.

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References

McNamara N, Gallup M, Sucher A, Maltseva I, McKemy D, Basbaum C . AsialoGM1 and TLR5 cooperate in flagellin-induced nucleotide signaling to activate Erk1/2. Am J Respir Cell Mol Biol. 2006; 34(6):653-60. PMC: 2644226. DOI: 10.1165/rcmb.2005-0441OC. View

Forslund S, Chakaroun R, Zimmermann-Kogadeeva M, Marko L, Aron-Wisnewsky J, Nielsen T . Combinatorial, additive and dose-dependent drug-microbiome associations. Nature. 2021; 600(7889):500-505. DOI: 10.1038/s41586-021-04177-9. View

Bailen M, Bressa C, Martinez-Lopez S, Gonzalez-Soltero R, Lominchar M, San Juan C . Microbiota Features Associated With a High-Fat/Low-Fiber Diet in Healthy Adults. Front Nutr. 2021; 7:583608. PMC: 7775391. DOI: 10.3389/fnut.2020.583608. View

Zhang X, Zhao Y, Xu J, Xue Z, Zhang M, Pang X . Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Sci Rep. 2015; 5:14405. PMC: 4585776. DOI: 10.1038/srep14405. View

Biagi E, Franceschi C, Rampelli S, Severgnini M, Ostan R, Turroni S . Gut Microbiota and Extreme Longevity. Curr Biol. 2016; 26(11):1480-5. DOI: 10.1016/j.cub.2016.04.016. View

Zhang X, Coker O, Chu E, Fu K, Lau H, Wang Y . Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites. Gut. 2020; 70(4):761-774. PMC: 7948195. DOI: 10.1136/gutjnl-2019-319664. View

Yu Q, Huo J, Zhang Y, Liu K, Cai Y, Xiang T . Tamoxifen-induced hepatotoxicity via lipid accumulation and inflammation in zebrafish. Chemosphere. 2019; 239:124705. DOI: 10.1016/j.chemosphere.2019.124705. View

Paule B, Terry S, Kheuang L, Soyeux P, Vacherot F, De La Taille A . The NF-kappaB/IL-6 pathway in metastatic androgen-independent prostate cancer: new therapeutic approaches?. World J Urol. 2007; 25(5):477-89. DOI: 10.1007/s00345-007-0175-6. View

Fruge A, Van Der Pol W, Rogers L, Morrow C, Tsuruta Y, Demark-Wahnefried W . 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. 2018; 120(4):650-659. PMC: 6509025. DOI: 10.1016/j.jand.2018.08.164. View

10.

Li C, Daling J, Porter P, Tang M, Malone K . Adjuvant hormonal therapy for breast cancer and risk of hormone receptor-specific subtypes of contralateral breast cancer. Cancer Res. 2009; 69(17):6865-70. PMC: 2745902. DOI: 10.1158/0008-5472.CAN-09-1355. View

11.

Shoaie S, Ghaffari P, Kovatcheva-Datchary P, Mardinoglu A, Sen P, Pujos-Guillot E . Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome. Cell Metab. 2015; 22(2):320-31. DOI: 10.1016/j.cmet.2015.07.001. View

12.

Ngan N, Mai N, Tung N, Lan N, Tai L, Phu N . A randomized open label trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis. Wellcome Open Res. 2019; 4:8. PMC: 6381443. DOI: 10.12688/wellcomeopenres.15010.1. View

13.

Magrone T, Jirillo E . The interaction between gut microbiota and age-related changes in immune function and inflammation. Immun Ageing. 2013; 10(1):31. PMC: 3848811. DOI: 10.1186/1742-4933-10-31. View

14.

Reiman D, Farhat A, Dai Y . Predicting Host Phenotype Based on Gut Microbiome Using a Convolutional Neural Network Approach. Methods Mol Biol. 2020; 2190:249-266. DOI: 10.1007/978-1-0716-0826-5_12. View

15.

Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson E . Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018; 555(7698):623-628. PMC: 6108420. DOI: 10.1038/nature25979. View

16.

Cani P, de Vos W . Next-Generation Beneficial Microbes: The Case of . Front Microbiol. 2017; 8:1765. PMC: 5614963. DOI: 10.3389/fmicb.2017.01765. View

17.

Gierach G, Curtis R, Pfeiffer R, Mullooly M, Ntowe E, Hoover R . Association of Adjuvant Tamoxifen and Aromatase Inhibitor Therapy With Contralateral Breast Cancer Risk Among US Women With Breast Cancer in a General Community Setting. JAMA Oncol. 2016; 3(2):186-193. PMC: 5757540. DOI: 10.1001/jamaoncol.2016.3340. View

18.

Goedert J, Jones G, Hua X, Xu X, Yu G, Flores R . Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study. J Natl Cancer Inst. 2015; 107(8). PMC: 4554191. DOI: 10.1093/jnci/djv147. View

19.

Qu Y, Misaghi S, Newton K, Maltzman A, Izrael-Tomasevic A, Arnott D . NLRP3 recruitment by NLRC4 during Salmonella infection. J Exp Med. 2016; 213(6):877-85. PMC: 4886354. DOI: 10.1084/jem.20132234. View

20.

Jellbauer S, Raffatellu M . An intestinal arsonist: pathobiont ignites IBD and flees the scene. Gut. 2013; 63(7):1034-5. DOI: 10.1136/gutjnl-2013-305589. View