Leucovorin ameliorated methotrexate induced intestinal toxicity via modulation of the gut microbiota. 2020

Xinyi Huang, and Qing Fang, and Tai Rao, and Luping Zhou, and Xiangchang Zeng, and Zhirong Tan, and Lulu Chen, and Dongsheng Ouyang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, PR China; Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 411000, PR China.

Methotrexate (MTX) is a widely used therapeutic agent for the treatment of cancer and autoimmune diseases. However, its efficacy is often limited by adverse effects, such as intestinal toxicity. Although treatment with leucovorin (LV) is the most common method to reduce the toxic effects of MTX, it may also compromise the therapeutic effects of MTX. The gut microbiome has been reported to be associated with the intestinal toxicity of MTX. In this study, the intestinal damage of MTX was ameliorated by treatment with LV. Moreover, the population, diversity, and principal components of the gut microbiota in MTX-treated mice were restored by treatment with LV. The only element of the gut microbiota that was significantly changed after treatment with LV was Bifidobacterium, and supplementation with Bifidobacterium longum ameliorated MTX-induced intestinal damage. In conclusion, our results suggest that the balance and the composition of gut microbiota have an important role in the LV-mediated protection against MTX-induced intestinal toxicity. This work provides foundation of data in support of a new potential mechanism for the prevention of MTX-induced intestinal toxicity.

UI MeSH Term Description Entries
D007410 Intestinal Diseases Pathological processes in any segment of the INTESTINE from DUODENUM to RECTUM. Disease, Intestinal,Diseases, Intestinal,Intestinal Disease
D008297 Male Males
D008727 Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D002955 Leucovorin The active metabolite of FOLIC ACID. Leucovorin is used principally as an antidote to FOLIC ACID ANTAGONISTS. Calcium Leucovorin,Citrovorum Factor,Folinic Acid,N(5)-Formyltetrahydrofolate,5-Formyltetrahydrofolate,5-Formyltetrahydropteroylglutamate,Calcium Folinate,Folinic Acid-SF,Leucovorin, (D)-Isomer,Leucovorin, (DL)-Isomer,Leucovorin, (R)-Isomer,Leucovorin, Calcium (1:1) Salt,Leucovorin, Calcium (1:1) Salt, (DL)-Isomer,Leucovorin, Calcium (1:1) Salt, Pentahydrate,Leucovorin, Monosodium Salt,Leukovorin,Leukovorum,Wellcovorin,5 Formyltetrahydrofolate,5 Formyltetrahydropteroylglutamate,Acid, Folinic,Factor, Citrovorum,Folinate, Calcium,Folinic Acid SF,Leucovorin, Calcium,Monosodium Salt Leucovorin
D003106 Colon The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON. Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental
D004269 DNA, Bacterial Deoxyribonucleic acid that makes up the genetic material of bacteria. Bacterial DNA
D000069196 Gastrointestinal Microbiome All of the microbial organisms that naturally exist within the GASTROINTESTINAL TRACT. Enteric Bacteria,Gastric Microbiome,Gastrointestinal Flora,Gastrointestinal Microbial Community,Gastrointestinal Microbiota,Gastrointestinal Microflora,Gut Flora,Gut Microbiome,Gut Microbiota,Gut Microflora,Intestinal Flora,Intestinal Microbiome,Intestinal Microbiota,Intestinal Microflora,Bacteria, Enteric,Flora, Gastrointestinal,Flora, Gut,Flora, Intestinal,Gastric Microbiomes,Gastrointestinal Microbial Communities,Gastrointestinal Microbiomes,Gastrointestinal Microbiotas,Gut Microbiomes,Gut Microbiotas,Intestinal Microbiomes,Intestinal Microbiotas,Microbial Community, Gastrointestinal,Microbiome, Gastric,Microbiome, Gastrointestinal,Microbiome, Gut,Microbiome, Intestinal,Microbiota, Gastrointestinal,Microbiota, Gut,Microbiota, Intestinal,Microflora, Gastrointestinal,Microflora, Gut,Microflora, Intestinal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001644 Bifidobacterium A rod-shaped, gram-positive, non-acid-fast, non-spore-forming, non-motile bacterium that is a genus of the family Bifidobacteriaceae, order Bifidobacteriales, class ACTINOBACTERIA. It inhabits the intestines and feces of humans as well as the human vagina.

Related Publications

Xinyi Huang, and Qing Fang, and Tai Rao, and Luping Zhou, and Xiangchang Zeng, and Zhirong Tan, and Lulu Chen, and Dongsheng Ouyang
September 2023, Foods (Basel, Switzerland),
Xinyi Huang, and Qing Fang, and Tai Rao, and Luping Zhou, and Xiangchang Zeng, and Zhirong Tan, and Lulu Chen, and Dongsheng Ouyang
June 2017, Nature reviews. Gastroenterology & hepatology,
Xinyi Huang, and Qing Fang, and Tai Rao, and Luping Zhou, and Xiangchang Zeng, and Zhirong Tan, and Lulu Chen, and Dongsheng Ouyang
January 2022, Frontiers in immunology,
Xinyi Huang, and Qing Fang, and Tai Rao, and Luping Zhou, and Xiangchang Zeng, and Zhirong Tan, and Lulu Chen, and Dongsheng Ouyang
January 2022, Frontiers in pharmacology,
Xinyi Huang, and Qing Fang, and Tai Rao, and Luping Zhou, and Xiangchang Zeng, and Zhirong Tan, and Lulu Chen, and Dongsheng Ouyang
April 2024, Food & function,
Xinyi Huang, and Qing Fang, and Tai Rao, and Luping Zhou, and Xiangchang Zeng, and Zhirong Tan, and Lulu Chen, and Dongsheng Ouyang
December 2023, Molecular nutrition & food research,
Xinyi Huang, and Qing Fang, and Tai Rao, and Luping Zhou, and Xiangchang Zeng, and Zhirong Tan, and Lulu Chen, and Dongsheng Ouyang
January 2022, Frontiers in immunology,
Xinyi Huang, and Qing Fang, and Tai Rao, and Luping Zhou, and Xiangchang Zeng, and Zhirong Tan, and Lulu Chen, and Dongsheng Ouyang
January 2019, Journal of immunology research,
Xinyi Huang, and Qing Fang, and Tai Rao, and Luping Zhou, and Xiangchang Zeng, and Zhirong Tan, and Lulu Chen, and Dongsheng Ouyang
January 2023, FEMS microbiology letters,
Xinyi Huang, and Qing Fang, and Tai Rao, and Luping Zhou, and Xiangchang Zeng, and Zhirong Tan, and Lulu Chen, and Dongsheng Ouyang
November 2020, Gut microbes,
Copied contents to your clipboard!