The Optimisticc team is supported through the Cancer Grand Challenges initiative. Learn more here

WP4: Model systems to study the colorectal cancer microbiome

The Clevers lab has been using their human ‘mini-gut’ technology. These mini guts (a.k.a. intestinal organoids) are grown in a dish from healthy gut stem cells. They can be expanded indefinitely and create miniature versions of the human gut. It has turned out that it is possible to chronically expose these mini-guts to potentially carcinogenic bacteria by weekly injections of these bacteria into the interior of the mini-guts. 

 Several bacterial species that are frequently found in the human intestines are suspected to contribute to the occurrence of colon cancer. One of these is a special strain (“pks”) of the best-known gut bug, E coli. In a collaboration with several other members of the consortium, it was shown that pks E coli induces unique and easily recognizable changes (‘mutations’) in the DNA of the human mini-gut cells. The same mutational signature was subsequently found to be present in the DNA of a significant fraction of human colon cancers. This ‘smoking gun’ implies that pks E coli is involved in the occurrence of a subset of human colon cancers  

 The Garrett Lab studies intestinal microbes and how their metabolites affect the development of bowel cancer. Short-chain fatty acids are metabolites generated by intestinal microbes from dietary fiber. In a recent publication, the Garrett Lab investigated the mechanisms by which free fatty acid receptor 2 (FFAR2), a receptor for short-chain fatty acids expressed by cancer cells and immune cells within the tumor microenvironment, afford protection from the development and progression of bowel cancer.

Work Package Leaders

Wendy Garrett, MD, PhD

Wendy Garrett, MD, PhD

Co-Principal InvestigatorHarvard TH Chan School of Public Health/Harvard Medical School

Professor of Immunology and Infectious Diseases

Hans Clevers, MD, PhD

Hans Clevers, MD, PhD

Co-Investigator, ubrecht Institute, University Medical Center Utrecht, Princess Maxima Centre for Pediatric Oncology

  • Professor of Molecular Genetics, University Medical Center Utrecht
  • Principal Investigator at the Hubrecht Institute (KNAW) and the Princess Máxima Center for Pediatric Oncology
Prof Fiona Powrie, FRS

Prof Fiona Powrie, FRS

Co-Investigator, University of Oxford

Director Kennedy Institute of Rheumatology, Translational
Gastroenterology Unit, Experimental Medicine Division Professor of
Microbiology & Immunology

Learn about other Work Packages

WP1: The Microbiome in colorectal cancer risk

WP1: The Microbiome in colorectal cancer risk

WP1: The Microbiome in colorectal cancer riskWe are analyzing the microbiome of 3000 bowel tumors, to determine the relationship between the bacteria within tumors and their mutations. We have analyzed the microbiome of over 2288 bowel cancer screening samples. Our...

WP 2: Epidemiological correlates of the colorectal cancer microbiome

WP 2: Epidemiological correlates of the colorectal cancer microbiome

WP2: Epidemiological correlates of the colorectal cancer microbiomeColorectal cancer (CRC) most often occurs sporadically (as compared to genetic forms of the disease) and is one of the leading causes of cancer-related death worldwide. Environmental factors contribute...

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