Aspirin Modulation of the Colorectal Cancer-Associated Microbe Fusobacterium nucleatum
| Autor: | Geicho Nakatsu, Jonathan N. Glickman, David A. Drew, Robert E. Schoen, Caitlin A. Brennan, Wendy S. Garrett, Carey Ann Gallini Comeau, Andrew T. Chan |
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| Rok vydání: | 2021 |
| Předmět: |
Adenoma
Male Colorectal cancer Carcinogenesis Colon Colorectal adenoma medicine.disease_cause Microbiology 03 medical and health sciences Mice Virology Medicine Animals Humans Microbiome 030304 developmental biology 0303 health sciences Aspirin biology Bacteria Fusobacterium nucleatum 030306 microbiology business.industry Cancer biology.organism_classification medicine.disease QR1-502 digestive system diseases stomatognathic diseases Cell Transformation Neoplastic colon cancer Cancer research Female business Colorectal Neoplasms medicine.drug Research Article |
| Zdroj: | mBio mBio, Vol 12, Iss 2 (2021) |
| ISSN: | 2150-7511 |
| Popis: | There is an increasing understanding of the clinical correlations and potential mechanistic roles of specific members of the gut and tumoral microbiota in colorectal cancer (CRC) initiation, progression, and survival. However, we have yet to parlay this knowledge into better CRC outcomes through microbially informed diagnostic, preventive, or therapeutic approaches. Aspirin is a chemopreventive agent for colorectal adenoma and cancer (CRC) that, like many drugs inclusive of chemotherapeutics, has been investigated for its effects on bacterial growth and virulence gene expression. Given the evolving recognition of the roles for bacteria in CRC, in this work, we investigate the effects of aspirin with a focus on one oncomicrobe—Fusobacterium nucleatum. We show that aspirin and its primary metabolite salicylic acid alter F. nucleatum strain Fn7-1 growth in culture and that aspirin can effectively kill both actively growing and stationary Fn7-1. We also demonstrate that, at levels that do not inhibit growth, aspirin influences Fn7-1 gene expression. To assess whether aspirin modulation of F. nucleatum may be relevant in vivo, we use the ApcMin/+ mouse intestinal tumor model in which Fn7-1 is orally inoculated daily to reveal that aspirin-supplemented chow is sufficient to inhibit F. nucleatum-potentiated colonic tumorigenesis. We expand our characterization of aspirin sensitivity across other F. nucleatum strains, including those isolated from human CRC tissues, as well as other CRC-associated microbes, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli. Finally, we determine that individuals who use aspirin daily have lower fusobacterial abundance in colon adenoma tissues, as determined by quantitative PCR performed on adenoma DNA. Together, our data support that aspirin has direct antibiotic activity against F. nucleatum strains and suggest that consideration of the potential effects of aspirin on the microbiome holds promise in optimizing risk-benefit assessments for use of aspirin in CRC prevention and management. |
| Databáze: | OpenAIRE |
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