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| Status |
Public on Aug 23, 2022 |
| Title |
Bacteria modulate tamoxifen-induced death via host fatty acid metabolism |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Our microbiota affects numerous processes involved in development, health, and the response to chemotherapeutic drugs. Tamoxifen is a selective estrogen receptor (ER) modulator that is used to treat ER positive breast cancer, but that at high doses kills both ER positive and ER-negative breast cancer cells. We recapitulate this off-target effect in Caenorhabditis elegans, which does not have an ER ortholog. We find that different bacteria dramatically modulate tamoxifen toxicity in C. elegans, with a three-order of magnitude difference between animals fed Escherichia coli, Comamonas aquatica, and Bacillus subtilis. Remarkably, host fatty acid (FA) biosynthesis mitigates tamoxifen toxicity, and different bacteria provide the animal with different FAs, resulting in distinct FA profiles. Surprisingly these bacteria modulate tamoxifen toxicity by different death mechanisms, some of which are modulated by FA supplementation and others by antioxidants. Together, this work reveals a complex interplay between bacteria, FA metabolism and tamoxifen toxicity that may provide a blueprint for similar studies in more complex mammals.
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| Overall design |
C. elegans RNA-sequencing of three experiments. Animals were treated with 400 µM citrate or 400 µM tamoxifen for 48 hours in biological triplicate.
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| Contributor(s) |
Diot C, Walhout AJ |
| Citation(s) |
36151093 |
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| Submission date |
Oct 28, 2021 |
| Last update date |
Oct 26, 2022 |
| Contact name |
Hefei Zhang |
| E-mail(s) |
hefei.zhang@umassmed.edu
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| Phone |
5083040127
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| Organization name |
University of Massachusetts Chan Medical School
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| Department |
Department of Systems Biology
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| Lab |
Albertha,J,Walhout
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| Street address |
4 Miles Ave
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| City |
Worcester |
| State/province |
Massachusetts |
| ZIP/Postal code |
01545 |
| Country |
USA |
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| Platforms (1) |
| GPL30091 |
DNBSEQ-G400 (Caenorhabditis elegans) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA776017 |
| SRA |
SRP343657 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE186785_citrate_tamoxifen_TPM.txt.gz |
380.8 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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