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The impact of gut microbiota manipulation with antibiotics on colon tumorigenesis in a murine model

Title
The impact of gut microbiota manipulation with antibiotics on colon tumorigenesis in a murine model
Author
은창수
Keywords
INFLAMMATORY-BOWEL-DISEASE; LOW-GRADE DYSPLASIA; ULCERATIVE-COLITIS; INTESTINAL INFLAMMATION; CANCER; MANAGEMENT; FATE
Issue Date
2019-12
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v. 14, no. 12, article no. e0226907
Abstract
It has been suggested that manipulation of gut microbiota using antibiotics can inhibit colitis-associated colorectal cancer (CAC) in a mouse model. We investigated whether timing of gut microbial manipulation using antibiotics affects colon tumorigenesis in the azoxy-methane (AOM)/dextran sodium sulfate (DSS)-induced CAC model. CAC was induced in C57BL/6 mice by injection of 12.5 mg/kg AOM followed by three rounds of 1.7% DSS exposure. There were six groups based on timing of antibiotic administration. Colonic inflammation, proliferation, and tumorigenesis were evaluated after animal sacrifice. High-throughput sequencing of the mice feces was performed to characterize changes in gut microbiota. Full-time antibiotic treatment significantly decreased the number and size of tumors, histological scores, and expression of pro-inflammatory cytokines compared to the AOM/DSS group without antibiotic treatment. The early and late antibiotic groups, antibiotic administration from the first and second rounds of DSS to the end of the study, showed significantly lower histological scores and tumor burden. In contrast, the pretreatment antibiotic group, antibiotic administration from 3 weeks prior to AOM to the first round of DSS, did not exhibit decreased tumorigenesis. Principal coordinate analysis showed similar gut microbial community structures among the full-time, early, and late antibiotic groups, whereas other groups showed distinct gut microbial profiles. There was a positive correlation between number of tumors and number of operational taxonomic units. Colonic tumorigenesis was attenuated by antibiotic administration, except for that only prior to DSS administration, suggesting that gut microbial changes should be maintained throughout the entire period of inflammation to suppress tumorigenesis.
URI
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226907https://repository.hanyang.ac.kr/handle/20.500.11754/156893
ISSN
1932-6203
DOI
10.1371/journal.pone.0226907
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COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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