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

Association between serum short-chain fatty acid levels and the risk of all-cause and cardiovascular disease mortality in Chinese patients undergoing maintenance hemodialysis: a retrospective cohort study
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
Mechanism of the AMPK/SIRT1 pathway in gut dysbiosis–mediated postoperative cognitive dysfunction in aged mice
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
Distribution and roles of Ligilactobacillus murinus in hosts
Zhou Chuandong, Jicong Hu, Jiawen Li, Yuting Wu, Chan Wu, Guanxi Lai, Han Shen, Fenglin Wu, Changli Tao, Song Liu, Wenfeng Zhang, Hongwei Shao
Microbiological Research.2024; 282: 127648. CrossRef
Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis
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
Chinese Science Bulletin.2024; 69(35): 5142. CrossRef
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
Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef
Targeting metabolic pathways: a novel therapeutic direction for type 2 diabetes
Zhihui Song, An Yan, Zehui Guo, Yuhang Zhang, Tao Wen, Zhenzhen Li, Zhihua Yang, Rui Chen, Yi Wang
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef

6,859 View
230 Download
9 Web of Science
11 Crossref

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

Citations to this article as recorded by

The Role of Gut Microbiota Dysbiosis in Erectile Dysfunction: From Pathophysiology to Treatment Strategies
Aris Kaltsas, Ilias Giannakodimos, Eleftheria Markou, Konstantinos Adamos, Marios Stavropoulos, Zisis Kratiras, Athanasios Zachariou, Fotios Dimitriadis, Nikolaos Sofikitis, Michael Chrisofos
Microorganisms.2025; 13(2): 250. CrossRef
The Antioxidant and Chemopreventive Activity of a Nutraceutical Derived from Brassicaceae Seed Extracts for Colorectal Cancer
Ana Guzmán-Carrasco, Cristina Mesas, Kevin Doello, Jesús M. Porres, Alejandro García-Beltrán, Rosario Martínez, Francisco Bermúdez, Mercedes Peña, Consolación Melguizo, Jose Prados
Nutrients.2025; 17(8): 1358. CrossRef
AI for rapid identification of major butyrate-producing bacteria in rhesus macaques (Macaca mulatta)
Annemiek Maaskant, Donghyeok Lee, Huy Ngo, Roy C. Montijn, Jaco Bakker, Jan A. M. Langermans, Evgeni Levin
Animal Microbiome.2025;[Epub] CrossRef
Juvenile Rats Exposed to Antibiotics Early in Life Display Sexual Dimorphisms on Social Behaviour and Sex Hormone Deconjugating Activity
Ivanka M. Kuehnel, Cristofer E. González‐Irarrázabal, Renato Pardo, Marcela Julio‐Pieper, Javier A. Bravo
Journal of Neurochemistry.2025;[Epub] CrossRef
Delineating the fecal microbiome of healthy domestic short-hair cats in South Korea
Hyun-Young Cho, Hyung-Joon Park, Jin-Sik Choi, Se-Hoon Kim, Min-Ok Ryu, Kyoung-Won Seo
Frontiers in Veterinary Science.2025;[Epub] CrossRef
Sexual dimorphism in colon is mediated by an androgen-IL33+ stromal cell axis
Haoyu Wang, Baowei Jing, Juan Zou, Tian Lan, Mengxin Hu, Lan Lin, Hanhua Cheng, Rongjia Zhou
Cell & Bioscience.2025;[Epub] CrossRef
Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis
Zihong Wu, Yuqing Huang, Renyi Zhang, Chuan Zheng, Fengming You, Min Wang, Chong Xiao, Xueke Li
Cell Communication and Signaling.2024;[Epub] CrossRef
Comparison of the fecal bacterial microbiota in mice, rats, and pigs after oral administration of alpha-glycosyl isoquercitrin
Hong Liu, Ryo Inoue, Mihoko Koyanagi, Shim-mo Hayashi, Gen Watanabe, Kentaro Nagaoka
The Journal of Toxicological Sciences.2024; 49(4): 151. CrossRef
Gut Microbes in Polycystic Ovary Syndrome and Associated Comorbidities; Type 2 Diabetes, Non-Alcoholic Fatty Liver Disease (NAFLD), Cardiovascular Disease (CVD), and the Potential of Microbial Therapeutics
Vineet Singh, Kanika Mahra, DaRyung Jung, Jae-Ho Shin
Probiotics and Antimicrobial Proteins.2024; 16(5): 1744. CrossRef
Role of sex steroids in colorectal cancer: pathomechanisms and medical applications
Jianglan Wu
American Journal of Cancer Research.2024; 14(7): 3200. CrossRef
Gender-affirming hormonal therapy induces a gender-concordant fecal metagenome transition in transgender individuals
Timur Liwinski, Matthias K. Auer, Johanna Schröder, Ina Pieknik, Christian Casar, Dorothee Schwinge, Lara Henze, Günter K. Stalla, Undine E. Lang, Alina von Klitzing, Peer Briken, Thomas Hildebrandt, Jeanne C. Desbuleux, Sarah V. Biedermann, Paul-Martin H
BMC Medicine.2024;[Epub] CrossRef
N-acyl glycines produced by commensal bacteria potentiate GLP-1 secretion as GPCR ligands
Anna Drzazga, Przemysław Bernat, Adriana Nowak, Marcin Szustak, Eliza Korkus, Edyta Gendaszewska-Darmach, Maria Koziołkiewicz
Biomedicine & Pharmacotherapy.2024; 180: 117467. CrossRef
Role of intestinal testosterone-degrading bacteria and 3/17β-HSD in the pathogenesis of testosterone deficiency-induced hyperlipidemia in males
Jun Tao, Wen Dai, Yongnan Lyu, Hang Liu, Juan Le, Ting Sun, Qian Yao, Zhiming Zhao, Xuejun Jiang, Yan Li
npj Biofilms and Microbiomes.2024;[Epub] CrossRef
Sexual dimorphism of gut microbiota in colorectal cancer
Zihong Wu, Ziming Wang, Jiamei Wang, Chong Xiao, Fengming You, Xueke Li
Chinese Science Bulletin.2024; 69(35): 5142. CrossRef
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
Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef
From-Toilet-to-Freezer: A Review on Requirements for an Automatic Protocol to Collect and Store Human Fecal Samples for Research Purposes
Frances Widjaja, Ivonne M. C. M. Rietjens
Biomedicines.2023; 11(10): 2658. CrossRef
Murine models of colorectal cancer: the azoxymethane (AOM)/dextran sulfate sodium (DSS) model of colitis-associated cancer
Dzhuliia Dzhalilova, Natalia Zolotova, Nikolai Fokichev, Olga Makarova
PeerJ.2023; 11: e16159. CrossRef

10,873 View
253 Download
19 Web of Science
17 Crossref

First
Prev
Page of 1
Next
Last

Search