Journal
NATURE CANCER
Volume 1, Issue 7, Pages 723-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s43018-020-0078-7
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Funding
- NIH [R01DK073338, TL1TR001428]
- University of Florida Health Cancer Center Funds
- University of Florida Department of Medicine Gatorade Fund
- Crohn's & Colitis Foundation of America research fellowship award [409472]
- UF Health Cancer Center Funds
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Intestinal inflammation and microbiota are two important components of colorectal cancer (CRC) etiology. However, it is not clear how tuning inflammation using clinically relevant anti-inflammatory treatment impacts microbiota or whether this consequently influences CRC outcome. Here, using chemically induced (DSS/Apc(min/+)) and spontaneous (Apc(min/+);Il10(-/-)) mouse CRC models colonized by colibactin-producing Escherichia coli, we established the role of microbiota in mediating the antitumorigenic effect of anti-tumor necrosis factor (TNF) therapy. We found that TNF blockade attenuated colitis and CRC development. Microbiota community structure and gene activities significantly changed with disease development, which was prevented by TNF blockade. Several microbiota functional pathways underwent similar changes in patients following anti-TNF therapy. Under cohousing condition, TNF blockade failed to prevent colitis, cancer development and disease-associated microbiota structural changes. Finally, microbiota transplantation showed reduced carcinogenic activity of microbiota from anti-TNF-treated mice. Together, our data demonstrate the plasticity of microbiota, which could be reverted to noncarcinogenic status by targeting inflammation. Jobin and colleagues show that targeting inflammation with TNF therapy has a preventative effect on carcinogenic activity of the microbiota in mouse models of colitis-associated colorectal cancer.
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