Cancer Research and Treatment

Original Articles

Hematologic malignancy

Higher Microbial Abundance and Diversity in Bronchus-Associated Lymphoid Tissue Lymphomas Than in Non-cancerous Lung Tissues: Jung Heon Kim, Jae Sik Kim, Noorie Choi, Jiwon Koh, Yoon Kyung Jeon, Ji Hyun Chang, Eung Soo Hwang, Il Han Kim; Cancer Res Treat. 2025;57(2):580-589. Published online September 30, 2024; DOI: https://doi.org/10.4143/crt.2024.689

Abstract PDF Supplementary Material PubReader ePub: Purpose
It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation next-generation sequencing (NGS) method.
Materials and Methods
DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed.
Results
Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues.
Conclusion
This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

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Clinical Impact of Microbiome Characteristics in Treatment-Naïve Extranodal NK/T-Cell Lymphoma Patients: Sang Eun Yoon, Woorim Kang, Junhun Cho, Mauricio Chalita, Je Hee Lee, Dong-Wook Hyun, Hyun Kim, Seok Jin Kim, Won Seog Kim; Cancer Res Treat. 2025;57(2):597-611. Published online August 16, 2024; DOI: https://doi.org/10.4143/crt.2024.675

Abstract PDF Supplementary Material PubReader ePub: Purpose
Extranodal natural killer/T-cell lymphoma (ENKTL) predominantly manifests in East Asia and Latin America. Despite shared intrinsic factors, such as ethnic and genetic backgrounds, the progression of ENKTL can be influenced by extrinsic factors related to changing lifestyle patterns.
Materials and Methods
This study collected stool samples from newly diagnosed (ND)–ENKTL patients (n=40) and conducted whole genome shotgun sequencing.
Results
ND-ENKTL revealed reduced alpha diversity in ND-ENKTL compared to healthy controls (HCs) (p=0.008), with Enterobacteriaceae abundance significantly contributing to the beta diversity difference between ENKTL and HCs (p < 0.001). Functional analysis indicated upregulated aerobic metabolism and degradation of aromatic compounds in ND-ENKTL. Enterobacteriaceae were associated not only with clinical data explaining disease status (serum C-reactive protein, stage, prognosis index of natural killer cell lymphoma [PINK], and PINK-E) but also with clinical outcomes (early relapse and short progression-free survival). The relative abundance of Enterobacteriaceae at the family level was similar between ENKTL and diffuse large B-cell lymphoma (DLBCL) (p=0.140). However, the ENKTL exhibited a higher abundance of Escherichia, in contrast to the prevalence of Enterobacter and Citrobacter in DLBCL. Linear regression analysis demonstrated a significant association between Escherichia abundance and programmed cell death-ligand-1 (PD-L1) levels in tissue samples (p=0.025), whereas no correlation with PD-L1 was observed for Enterobacteriaceae at the family level (p=0.571).
Conclusion
ND-ENKTL exhibited an abundance of Enterobacteriaceae and a dominant presence of Escherichia. These microbial characteristics correlated with disease status, treatment outcomes, and PD-L1 expression, suggesting the potential of the ENKTL microbiome as a biomarker and cause of lymphomagenesis, which warrants further exploration.

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Gastrointestinal cancer

Fecal Microbial Dysbiosis Is Associated with Colorectal Cancer Risk in a Korean Population: Jeongseon Kim, Madhawa Gunathilake, Hyun Yang Yeo, Jae Hwan Oh, Byung Chang Kim, Nayoung Han, Bun Kim, Hyojin Pyun, Mi Young Lim, Young-Do Nam, Hee Jin Chang; Cancer Res Treat. 2025;57(1):198-211. Published online July 26, 2024; DOI: https://doi.org/10.4143/crt.2024.382

Abstract PDF Supplementary Material PubReader ePub

Purpose
The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking.
Materials and Methods
In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2.
Results
There is a significant divergence of the microbial composition between CRC patients and controls (permutational multivariate analysis of variance p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (odds ratio [OR], 6.93; 95% confidence interval [CI], 3.98 to 12.06; p-trend < 0.001) compared to those in the lowest tertile. Similar results were found for men (OR, 6.28; 95% CI, 3.04 to 12.98; p-trend < 0.001) and women (OR, 7.39; 95% CI, 3.10 to 17.63; p-trend < 0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples.
Conclusion
Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.

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Quantification of Naturally Occurring Prebiotics in Selected Foods
Arianna Natale, Federica Fiori, Federica Turati, Carlo La Vecchia, Maria Parpinel, Marta Rossi
Nutrients.2025; 17(4): 683. CrossRef

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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

Abstract PDF PubReader ePub

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.

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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
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

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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.

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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
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

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