Intestinal Research

Original Articles

Tumor

Impact of stool transplantation and metformin on polyp reduction and inflammation in an APC Min mouse model: Yeon Ji Kim, Jiwon Lee, Eunmi Lee, Seun Ja Park, Jae Hyun Kim; Intest Res 2025;23(3):382-389. Published online May 19, 2025; DOI: https://doi.org/10.5217/ir.2025.00011

Abstract PDF PubReader ePub: Background/Aims
Familial adenomatous polyposis is a hereditary condition characterized by numerous adenomatous polyps in the colon and rectum, significantly increasing colorectal cancer risk. Current management strategies, such as prophylactic colectomy, are invasive and have long-term consequences, highlighting the need for alternative therapies. This study aimed to evaluate whether stool transplantation and metformin therapy synergistically reduce polyp formation and inflammation.
Methods
APC Min mice were divided into 4 groups: control, anti-control (antibiotic pretreatment), stool (stool transplantation), and stool+metformin. Polyp burden, bacterial abundance, inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, IL-10), and tumorigenic markers (NF-κB, Cox2, c-myc, β-catenin) were assessed using messenger RNA (mRNA) and protein analyses of intestinal tissues, along with serum and fecal microbiota evaluations.
Results
Stool transplantation combined with metformin significantly reduced bacterial abundance and polyp burden. The anti-control group showed similar reductions, suggesting suppression of gut microbiota re-establishment. TNF-α and IL-10 levels remained unchanged, but a significant increase in IL-6 was observed in the stool+metformin group’s intestinal tissues, indicating localized immune activation. Intestinal Cox2 mRNA expression was reduced in the combination group, correlating with polyp suppression. Protein levels of NF-κB, Cox2, and β-catenin showed no significant changes in vivo, while in vitro experiments revealed a decrease in NF-κB and an increase in Cox2, suggesting complex regulation of inflammation-related pathways.
Conclusions
Stool transplantation combined with metformin reduces polyp burden in APC Min mice through gut microbiota modulation and localized immune activation. These findings support the therapeutic potential of this combination treatment for familial adenomatous polyposis.

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Inhibitory Effect of Metformin Therapy on the Incidence of Colorectal Advanced Adenomas in Patients With Diabetes: Yo Han Kim, Ran Noh, Sun Young Cho, Seong Jun Park, Soung Min Jeon, Hyun Deok Shin, Suk Bae Kim, Jeong Eun Shin; Intest Res 2015;13(2):145-152. Published online April 27, 2015; DOI: https://doi.org/10.5217/ir.2015.13.2.145

Abstract PDF PubReader

Background/Aims

Metformin use has been associated with decreased colorectal cancer risk and mortality among diabetic patients. Recent research suggests that metformin use may decrease the incidence of colorectal adenomas in diabetic patients with previous colorectal cancer. This study aimed to assess the clinical effect of metformin use on the development of colorectal adenomas in diabetic patients without previous colorectal cancer.

Methods

Among 604 consecutive diabetic patients who underwent colonoscopic surveillance after initial colonoscopy between January 2002 and June 2012, 240 patients without previous colorectal cancer were enrolled in this study and were divided in two groups: 151 patients receiving metformin and 89 patients not receiving metformin. Patient demographics and clinical characteristics as well as the colorectal adenoma incidence rate were retrospectively analyzed.

Results

The incidence rate of total colorectal adenomas was not different according to metformin use (P=0.349). However, the advanced adenoma incidence rate was significantly lower in the metformin group compared with the non-metformin group (relative risk [RR], 0.09; P=0.011). Metformin use was independently associated with a decreased incidence of advanced colorectal adenomas after adjustment for clinically relevant factors (RR, 0.072; P=0.016). In addition, the cumulative development rate of advanced adenomas during follow-up was significantly lower in the metformin group compared with the non-metformin group (P=0.007).

Conclusions

Metformin use in diabetic patients without previous colorectal cancer is associated with a lower risk of advanced colorectal adenomas.

Citations

Citations to this article as recorded by

Metformin for primary prevention of colorectal neoplasms in adenoma-free populations: a systematic review and dose-response meta-analysis
Mengdan Shen, Shan Lu, Zihao Xu, Feifei Zhou, Li-Ting Sheng, Qiang Yu
Frontiers in Pharmacology.2025;[Epub] CrossRef
Metformin Use Is Inversely Associated with Prevalent, but Not Incident Colorectal Adenomas
Anna Krigel, Snow Trinh T. Nguyen, Nawar Talukder, Ching-Ho Huang, Carlos Buitrago, Gabriel Karkenny, Benjamin Lebwohl, Julian A. Abrams, James L. Araujo
Digestive Diseases and Sciences.2022; 67(10): 4886. CrossRef
The Impact of Diabetes Mellitus on the Second Primary Malignancies in Colorectal Cancer Patients
Jana Halamkova, Tomas Kazda, Lucie Pehalova, Roman Gonec, Sarka Kozakova, Lucia Bohovicova, Ondrej Slaby, Regina Demlova, Marek Svoboda, Igor Kiss
Frontiers in Oncology.2021;[Epub] CrossRef
Suppressive effects of metformin on colorectal adenoma incidence and malignant progression
Min Deng, Siqin Lei, Dongdong Huang, Hui Wang, Shuli Xia, Enping Xu, Yihua Wu, Honghe Zhang
Pathology - Research and Practice.2020; 216(2): 152775. CrossRef
Metformin and colorectal cancer: a systematic review, meta-analysis and meta-regression
Cheng-Ann Winston Ng, Amy Aimei Jiang, Emma Min Shuen Toh, Cheng Han Ng, Zhi Hao Ong, Siyu Peng, Hui Yu Tham, Raghav Sundar, Choon Seng Chong, Chin Meng Khoo
International Journal of Colorectal Disease.2020; 35(8): 1501. CrossRef
Cirrhosis and insulin resistance: current knowledge, pathophysiological mechanisms, complications and potential treatments
Frédéric Clarembeau, Georgia Bale, Nicolas Lanthier
Clinical Science.2020; 134(16): 2117. CrossRef
Age at menarche and risk of colorectal adenoma
Nam Hee Kim, Jung Ho Park, Dong Il Park, Chong Il Sohn, Kyuyong Choi, Yoon Suk Jung
The Korean Journal of Internal Medicine.2019; 34(5): 998. CrossRef
Diabetes Mellitus: a Clinical Condition Associated with Metabolic Syndrome and Colorectal Cancer Risk
Vesna Brzacki, Aleksandar Nagorni, Manolis Kallistratos, Athanasios Manolis, Dragan Lovic
Current Pharmacology Reports.2019; 5(4): 205. CrossRef
Diabetes Mellitus and Colon Carcinogenesis: Expectation for Inhibition of Colon Carcinogenesis by Oral Hypoglycemic Drugs
Junichi Kato, Yohei Shirakami, Masahito Shimizu
Gastrointestinal Disorders.2019; 1(2): 273. CrossRef
Metformin Is Associated With Reduced Odds for Colorectal Cancer Among Persons With Diabetes
Joshua Demb, Armaan Yaseyyedi, Lin Liu, Ranier Bustamante, Ashley Earles, Pradipta Ghosh, J. Silvio Gutkind, Andrew J. Gawron, Tonya R. Kaltenbach, Maria Elena Martinez, Samir Gupta
Clinical and Translational Gastroenterology.2019; 10(11): e00092. CrossRef
Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects
Muhamad Noor Alfarizal Kamarudin, Md. Moklesur Rahman Sarker, Jin-Rong Zhou, Ishwar Parhar
Journal of Experimental & Clinical Cancer Research.2019;[Epub] CrossRef
Postoperative adjuvant chemotherapy is associated with a lower incidence of colorectal adenomas in patients with previous colorectal cancer
Hee Seung Lee, Sung Bae Kim, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Jae Hee Cheon, Won Ho Kim, Tae Il Kim
Gastrointestinal Endoscopy.2018; 87(3): 688. CrossRef
Metformin use and the risk of colorectal adenoma: A systematic review and meta‐analysis
Yoon Suk Jung, Chan Hyuk Park, Chang Soo Eun, Dong Il Park, Dong Soo Han
Journal of Gastroenterology and Hepatology.2017; 32(5): 957. CrossRef
The effect of metformin on the recurrence of colorectal adenoma in diabetic patients with previous colorectal adenoma
Min Seok Han, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Jae Hee Cheon, Won Ho Kim, Tae Il Kim
International Journal of Colorectal Disease.2017; 32(8): 1223. CrossRef
Ursodeoxycholic acid inhibits the proliferation of colon cancer cells by regulating oxidative stress and cancer stem-like cell growth
Eun-Kyung Kim, Jae Hee Cho, EuiJoo Kim, Yoon Jae Kim, Aamir Ahmad
PLOS ONE.2017; 12(7): e0181183. CrossRef
Serum CEA and CA 19-9 Levels are Associated with the Presence and Severity of Colorectal Neoplasia
Nam Hee Kim, Mi Yeon Lee, Jung Ho Park, Dong Il Park, Chong Il Sohn, Kyuyong Choi, Yoon Suk Jung
Yonsei Medical Journal.2017; 58(5): 918. CrossRef
Synergistic Benefit of Statin and Metformin in Gastrointestinal Malignancies
George K. Nimako, Zachary A. P. Wintrob, Dmitriy A. Sulik, Jennifer L. Donato, Alice C. Ceacareanu
Journal of Pharmacy Practice.2017; 30(2): 185. CrossRef
Risk Factors for False Fecal Immunochemical Test Results in Colorectal Cancer Screening
Nam Hee Kim, Jung Ho Park, Dong Il Park, Chong Il Sohn, Kyuyong Choi, Yoon Suk Jung
Journal of Clinical Gastroenterology.2017; 51(2): 151. CrossRef
Parameters of Glucose and Lipid Metabolism Affect the Occurrence of Colorectal Adenomas Detected by Surveillance Colonoscopies
Nam Hee Kim, Jung Yul Suh, Jung Ho Park, Dong Il Park, Yong Kyun Cho, Chong Il Sohn, Kyuyong Choi, Yoon Suk Jung
Yonsei Medical Journal.2017; 58(2): 347. CrossRef
Are Hemorrhoids Associated with False-Positive Fecal Immunochemical Test Results?
Nam Hee Kim, Jung Ho Park, Dong Il Park, Chong Il Sohn, Kyuyong Choi, Yoon Suk Jung
Yonsei Medical Journal.2017; 58(1): 150. CrossRef
Association Between Low Relative Muscle Mass and the Risk of Colorectal Neoplasms
Yoon Suk Jung, Nam Hee Kim, Seungho Ryu, Jung Ho Park, Dong Il Park, Chong Il Sohn
Journal of Clinical Gastroenterology.2017; 51(10): e83. CrossRef
Metformin therapy and the risk of colorectal adenoma in patients with type 2 diabetes: A meta-analysis
Yi-Chao Hou, Qiang Hu, Jiao Huang, Jing-Yuan Fang, Hua Xiong
Oncotarget.2017; 8(5): 8843. CrossRef
Metformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: A systematic review and meta-analysis
Feifei Liu, Lijing Yan, Zhan Wang, Yuanan Lu, Yuanyuan Chu, Xiangyu Li, Yisi Liu, Dongsheng Rui, Shaofa Nie, Hao Xiang
Oncotarget.2017; 8(9): 16017. CrossRef
Kaffee senkt Rückfallrate bei Patienten mit Kolonkarzinom im Stadium III
Michael Fink
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Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies
Vibha Rani, Gagan Deep, Rakesh K. Singh, Komaraiah Palle, Umesh C.S. Yadav
Life Sciences.2016; 148: 183. CrossRef
Weight Change and Obesity Are Associated with a Risk of Adenoma Recurrence
Yoon Suk Jung, Jung Ho Park, Dong Il Park, Chong Il Sohn, Kyuyong Choi
Digestive Diseases and Sciences.2016; 61(9): 2694. CrossRef

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26 Crossref

Does Metformin Affect The Incidence of Colonic Polyps and Adenomas in Patients with Type 2 Diabetes Mellitus?: Youn Hee Cho, Bong Min Ko, Shin Hee Kim, Yu Sik Myung, Jong Hyo Choi, Jae Pil Han, Su Jin Hong, Seong Ran Jeon, Hyun Gun Kim, Jin Oh Kim, Moon Sung Lee; Intest Res 2014;12(2):139-145. Published online April 29, 2014; DOI: https://doi.org/10.5217/ir.2014.12.2.139

Abstract PDF PubReader

Background/Aims

Colorectal cancer (CRC) develops from colonic adenomas. Type 2 diabetes mellitus (DM) is associated with a higher risk of CRC and metformin decreases CRC risk. However, it is not certain if metformin affects the development of colorectal polyps and adenomas. This study aimed to elucidate if metforminaffects the incidence of colonic polyps and adenomas in patients with type 2 DM.

Methods

Of 12,186 patients with type 2 DM, 3,775 underwent colonoscopy between May 2001 and March 2013. This study enrolled 3,105 of these patients, and divided them in two groups: 912 patients with metformin use and 2,193 patients without metformin use. Patient clinical characteristics, polyp and adenoma detection rate in the two groups were analyzed retrospectively.

Results

The Colorectal polyp detection rate was lower in the metformin group than in the non-meformin group (39.4% vs. 62.4%, P<0.01). Colorectal adenoma detection rate was significantly lower in the metformin group than in the non-metformin group (15.2% vs. 20.5%, P<0.01). Fewer advanced adenomas were detected in the metformin group than in the non-metformin group (12.2% vs. 22%, P<0.01). Multivariate analysis identified age, sex, Body mass index and metformin use as factors associated with polyp incidence, whereas only metforminwas independently associated with decreased adenoma incidence (Odd ratio=0.738, 95% CI=0.554-0.983, P=0.03).

Conclusions

In patients with type 2 DM, metformin reduced the incidence of adenomas that may transform into CRC. Therefore, metformin may be useful for the prevention of CRC in patients with type 2 DM.

Citations

Citations to this article as recorded by

Metformin for primary prevention of colorectal neoplasms in adenoma-free populations: a systematic review and dose-response meta-analysis
Mengdan Shen, Shan Lu, Zihao Xu, Feifei Zhou, Li-Ting Sheng, Qiang Yu
Frontiers in Pharmacology.2025;[Epub] CrossRef
Is Metformin Associated with a Lower Prevalence of Polyps, Adenomas, and Colorectal Carcinoma in Patients with Diabetes Mellitus?
Maria Inês Canha, Gonçalo Ramos, Rita Prata, Pedro Lages Martins, Marta Viúla Ramos, João Coimbra
Journal of Gastrointestinal Cancer.2024; 55(1): 435. CrossRef
Metformin administration in prevention of colorectal polyps in type 2 diabetes mellitus patients
Xiao-Qing Wu, Li-Hua Deng, Qian Xue, Xia Li, Meng-Han Li, Jing-Tong Wang
World Journal of Clinical Cases.2024; 12(20): 4206. CrossRef
Anti-cancer Efficacy of Metformin: Recent Updates on Breast and Other Cancers
Md. Imtiazul Kabir, Robin Kumar, Lakshmi Sai Pratyusha Bugata, Komal Raina
Current Pharmacology Reports.2023; 9(5): 284. CrossRef
Metformin Use Is Inversely Associated with Prevalent, but Not Incident Colorectal Adenomas
Anna Krigel, Snow Trinh T. Nguyen, Nawar Talukder, Ching-Ho Huang, Carlos Buitrago, Gabriel Karkenny, Benjamin Lebwohl, Julian A. Abrams, James L. Araujo
Digestive Diseases and Sciences.2022; 67(10): 4886. CrossRef
Effect of metformin on thyroid cancer risk in patients with acromegaly: A preliminary observational study
Cem Sulu, Ayyuce Begum Bektas, Suleyman Sami Guzel, Kubilay Tay, Serdar Sahin, Emre Durcan, Hande Mefkure Ozkaya, Pinar Kadioglu
Growth Hormone & IGF Research.2022; 66: 101484. CrossRef
Metformin Modifies the Gut Microbiota of Mice Infected with Helicobacter pylori
Marine Jauvain, Sarah Courtois, Philippe Lehours, Emilie Bessède
Pharmaceuticals.2021; 14(4): 329. CrossRef
Bovine Meat and Milk Factors (BMMFs): Their Proposed Role in Common Human Cancers and Type 2 Diabetes Mellitus
Ethel-Michele de Villiers, Harald zur Hausen
Cancers.2021; 13(21): 5407. CrossRef
Suppressive effects of metformin on colorectal adenoma incidence and malignant progression
Min Deng, Siqin Lei, Dongdong Huang, Hui Wang, Shuli Xia, Enping Xu, Yihua Wu, Honghe Zhang
Pathology - Research and Practice.2020; 216(2): 152775. CrossRef
Use of metformin and risk of breast and colorectal cancer
Gad Rennert, Hedy S. Rennert, Naomi Gronich, Mila Pinchev, Stephen B. Gruber
Diabetes Research and Clinical Practice.2020; 165: 108232. CrossRef
Diabetes Mellitus: a Clinical Condition Associated with Metabolic Syndrome and Colorectal Cancer Risk
Vesna Brzacki, Aleksandar Nagorni, Manolis Kallistratos, Athanasios Manolis, Dragan Lovic
Current Pharmacology Reports.2019; 5(4): 205. CrossRef
Diabetes Mellitus and Colon Carcinogenesis: Expectation for Inhibition of Colon Carcinogenesis by Oral Hypoglycemic Drugs
Junichi Kato, Yohei Shirakami, Masahito Shimizu
Gastrointestinal Disorders.2019; 1(2): 273. CrossRef
Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects
Muhamad Noor Alfarizal Kamarudin, Md. Moklesur Rahman Sarker, Jin-Rong Zhou, Ishwar Parhar
Journal of Experimental & Clinical Cancer Research.2019;[Epub] CrossRef
Postoperative adjuvant chemotherapy is associated with a lower incidence of colorectal adenomas in patients with previous colorectal cancer
Hee Seung Lee, Sung Bae Kim, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Jae Hee Cheon, Won Ho Kim, Tae Il Kim
Gastrointestinal Endoscopy.2018; 87(3): 688. CrossRef
Parameters of Glucose and Lipid Metabolism Affect the Occurrence of Colorectal Adenomas Detected by Surveillance Colonoscopies
Nam Hee Kim, Jung Yul Suh, Jung Ho Park, Dong Il Park, Yong Kyun Cho, Chong Il Sohn, Kyuyong Choi, Yoon Suk Jung
Yonsei Medical Journal.2017; 58(2): 347. CrossRef
Diabetes-induced mechanophysiological changes in the small intestine and colon
Mirabella Zhao, Donghua Liao, Jingbo Zhao
World Journal of Diabetes.2017; 8(6): 249. CrossRef
Metformin use and the risk of colorectal adenoma: A systematic review and meta‐analysis
Yoon Suk Jung, Chan Hyuk Park, Chang Soo Eun, Dong Il Park, Dong Soo Han
Journal of Gastroenterology and Hepatology.2017; 32(5): 957. CrossRef
Energy sensing pathways: Bridging type 2 diabetes and colorectal cancer?
Juhong Yang, Reiko Nishihara, Xuehong Zhang, Shuji Ogino, Zhi Rong Qian
Journal of Diabetes and its Complications.2017; 31(7): 1228. CrossRef
Metformin therapy and the risk of colorectal adenoma in patients with type 2 diabetes: A meta-analysis
Yi-Chao Hou, Qiang Hu, Jiao Huang, Jing-Yuan Fang, Hua Xiong
Oncotarget.2017; 8(5): 8843. CrossRef
Metformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: A systematic review and meta-analysis
Feifei Liu, Lijing Yan, Zhan Wang, Yuanan Lu, Yuanyuan Chu, Xiangyu Li, Yisi Liu, Dongsheng Rui, Shaofa Nie, Hao Xiang
Oncotarget.2017; 8(9): 16017. CrossRef
Therapeutic strategies against cancer stem cells in human colorectal cancer (Review)
Magdalena Szaryńska, Agata Olejniczak, Jarosław Kobiela, Piotr Spychalski, Zbigniew Kmieć
Oncology Letters.2017;[Epub] CrossRef
Potential Benefit of Metformin as Treatment for Colon Cancer: the Evidence so Far
Azza Ali Abdelsatir, Nazik Elmalaika Husain, Abdallah Tarig Hassan, Wadie M Elmadhoun, Ahmed O Almobarak, Mohamed H Ahmed
Asian Pacific Journal of Cancer Prevention.2016; 16(18): 8053. CrossRef
Weight Change and Obesity Are Associated with a Risk of Adenoma Recurrence
Yoon Suk Jung, Jung Ho Park, Dong Il Park, Chong Il Sohn, Kyuyong Choi
Digestive Diseases and Sciences.2016; 61(9): 2694. CrossRef
Associations between amount of smoking and alcohol intake and risk of colorectal neoplasm
Yoon Suk Jung, Hwanseok Jung, Kyung Eun Yun, Seungho Ryu, Yoosoo Chang, Dong Il Park, Kyuyong Choi
Journal of Gastroenterology and Hepatology.2016; 31(4): 788. CrossRef
Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer
Jessica K. Paulus, Christina D. Williams, Furha I. Cossor, Michael J. Kelley, Robert E. Martell
Cancer Epidemiology, Biomarkers & Prevention.2016; 25(10): 1418. CrossRef
Inhibitory Effect of Metformin Therapy on the Incidence of Colorectal Advanced Adenomas in Patients With Diabetes
Yo Han Kim, Ran Noh, Sun Young Cho, Seong Jun Park, Soung Min Jeon, Hyun Deok Shin, Suk Bae Kim, Jeong Eun Shin
Intestinal Research.2015; 13(2): 145. CrossRef

9,522 View
64 Download
31 Web of Science
26 Crossref

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