Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Anti–PD-L1 Antibody and/or 17β-Estradiol Treatment Induces Changes in the Gut Microbiome in MC38 Colon Tumor Model: Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Soo In Choi, Jae Young Jang, Jina Choi, Ha-Na Lee; Cancer Res Treat. 2023;55(3):894-909. Published online January 9, 2023; DOI: https://doi.org/10.4143/crt.2022.1427

Purpose
17β-Estradiol (E2) supplementation suppresses MC38 tumor growth by downregulating the expression of programmed death-ligand 1 (PD-L1). This study aims to figure out the gut microbiota that respond to anti–PD-L1 and/or estrogen treatment in MC38 colon cancer model.
Materials and Methods
A syngeneic colon tumor model was developed by injection of MC38 cells into C57BL/6 background male and female mice. Three days before MC38 cells injection, E2 was supplemented to male mice daily for 1 week. Male and female mice with MC38 tumors (50-100 mm3) were injected with anti–PD-L1 antibody. Fresh feces were collected 26 days after injection of MC38 cells and 16S rRNA metagenomics sequencing of DNA extracted from feces was used to assess gut microbial composition.
Results
At the taxonomic family level, Muribaculaceae was enriched only in the MC38 male control group. In male mice, linear discriminant analysis effect size analysis at the species level revealed that the four microorganisms were commonly regulated in single and combination treatment with anti–PD-L1 and/or E2; a decrease in PAC001068_g_uc and PAC001070_s (family Muribaculaceae) and increase in PAC001716_s and PAC001785_s (family Ruminococcaceae). Interestingly, in the anti–PD-L1 plus E2 group, a decrease in opportunistic pathogens (Enterobacteriaceae group) and an increase in commensal bacteria (Lactobacillus murinus group and Parabacteroides goldsteinii) were observed. Furthermore, the abundance of Parabacteroides goldsteinii was increased in both males and females in the anti–PD-L1 group.
Conclusion
Our results suggest that gut microbial changes induced by the pretreatment of estrogen before anti–PD-L1 might contribute to treatment of MC38 colon cancer.

Citations

Citations to this article as recorded by

Gut microbiome–driven colorectal cancer via immune, metabolic, neural, and endocrine axes reprogramming
Jhommara Bautista, Mónica Lamas-Maceiras, Camila Hidalgo-Tinoco, Antonio Guerra-Guerrero, Anapaula Betancourt-Velarde, Andrés López-Cortés
npj Biofilms and Microbiomes.2026;[Epub] CrossRef
Gastrointestinal cancers in women: The role of sex hormones
Amit Yadav, Usha Dutta
Indian Journal of Gastroenterology.2026; 45(2): 211. CrossRef
Wuda granules target estrogen receptors and modulate gut microbiota to alleviate postoperative ileus: A multi-omics perspective
Tao Wang, Yi-Hua Xu, Yang-Hui Ou, Wen-Jun Xiong, Li-Jie Luo, Jin Li, Yao-Hui Peng, Yan Chen, Hai-Ping Zeng, Yang Yu, Hai-Peng Tang, Fei Wang, Hong-Liang Yao, Wei Wang
World Journal of Gastroenterology.2026;[Epub] CrossRef
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Frontiers in Veterinary Science.2026;[Epub] CrossRef
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Food Research International.2026; 242: 119827. CrossRef
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Xiu-Nan Zhao, Shu-Xin Liu, Shuang Zhang, Zhen-Zhen Wang, Zi Lin, Xue-Lian Jian, Cui Dong, Yi-Nan Zhang
Clinical Kidney Journal.2025;[Epub] CrossRef
Parabacteroides as a promising target for disease intervention: current stage and pending issues
Jing Liu, Hui Qiu, Jiamin Zhao, Nan Shao, Chao Chen, Zhixu He, Xu Zhao, Juanjuan Zhao, Ya Zhou, Lin Xu
npj Biofilms and Microbiomes.2025;[Epub] CrossRef
Therapeutic potential of the gut commensal bacterium Parabacteroides goldsteinii in human health and disease treatment
Ziyun Li, Li Zhang, Zhenxia Wan, Huijuan Liu, Ting Zhang, Yan Li
Frontiers in Microbiology.2025;[Epub] CrossRef
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Fu Xu, Yang Yue, Defeng Sun
International Journal of Neuropsychopharmacology.2025;[Epub] CrossRef
Unveiling the interplay between microbiota and PD1/PD-L1 axis in tumor immunity and immunotherapy
Qiguang Lu, Jiasheng Wu, Xiaoyan Yu, Juanjuan Qian, Zhengwei Song
Frontiers in Immunology.2025;[Epub] CrossRef
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Zihong Wu, Yuqing Huang, Renyi Zhang, Chuan Zheng, Fengming You, Min Wang, Chong Xiao, Xueke Li
Cell Communication and Signaling.2024;[Epub] CrossRef
17β-estradiol in colorectal cancer: friend or foe?
Zihong Wu, Chong Xiao, Jiamei Wang, Min Zhou, Fengming You, Xueke Li
Cell Communication and Signaling.2024;[Epub] CrossRef
Sexual dimorphism of gut microbiota in colorectal cancer
Zihong Wu, Ziming Wang, Jiamei Wang, Chong Xiao, Fengming You, Xueke Li
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Direct and indirect effects of estrogens, androgens and intestinal microbiota on colorectal cancer
Zihong Wu, Yi Sun, Wenbo Huang, Zhenzhen Jin, Fengming You, Xueke Li, Chong Xiao
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Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef

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Changes in Gut Microbiome upon Orchiectomy and Testosterone Administration in AOM/DSS-Induced Colon Cancer Mouse Model: Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Soo In Choi, Jae Young Jang, Ha-Na Lee; Cancer Res Treat. 2023;55(1):196-218. Published online July 1, 2022; DOI: https://doi.org/10.4143/crt.2022.080

Abstract PDF Supplementary Material PubReader ePub

Purpose
Sex hormones are known to affect the gut microbiota. Previously, we reported that endogenous and exogenous testosterone are associated with colorectal cancer (CRC) development and submucosal invasion. In the present study, we investigated whether the gut microbiota is affected by orchiectomy (ORX) and testosterone propionate (TP) administration using an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC mouse model.
Materials and Methods
Gut microbiota was evaluated by means of 16S rRNA gene sequencing of stool DNA extracted from feces that were obtained at 13 weeks after AOM injection (from 22-week-old animals) and stored in a gas-generating pouch.
Results
The increase in microbial diversity (Chao1 and Phylogenetic Diversity index) and Firmicutes/Bacteroidetes (F/B) ratio upon AOM/DSS treatment in ORX mice was significantly decreased by TP supplementation. The ratio of commensal bacteria to opportunistic pathogens was lower in the TP-administered females and ORX mice than in the AOM/DSS group. Opportunistic pathogens (Mucispirillum schaedleri or Akkermansia muciniphila) were identified only in the TP group. In addition, microbial diversity and F/B ratio were higher in male controls than in female and ORX controls. Flintibacter butyricus, Ruminococcus bromii, and Romboutsia timonensis showed similar changes in the male control group as those in the female and ORX controls.
Conclusion
In conclusion, testosterone determines the dysbiosis of gut microbiota, which suggests that it plays a role in the sex-related differences in colorectal carcinogenesis.

Citations

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