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Manipulating the gut microbiome reduces cancer in mice

OCTOBER 23, 2018
Clinical Congress Daily Highlights, Tuesday Second Edition


New mouse studies suggest that manipulation of gut bacteria could form the basis of an important immunotherapeutic strategy against cancer.

Vrishketan Sethi, MD, University of Miami, FL, and colleagues examined the progression of cancer in mouse models with differing microbiome populations. In humans, the gut microbiome significantly outnumbers the human genome. While the latter is nonmodifiable, the microbiome changes with nutrition, age, geography, and disease state. Gut bacteria have also been found to shape our immunity and susceptibility to autoimmune disease, making them relevant to cancer treatment.

“They influence why only some of us will respond to immunotherapy,” Dr. Sethi said. 

Multiple cancers also present with changed “dysbiotic” gut microbiota, but it has been unclear if this dysbiotic state promotes cancer or is a neutral bystander.

Dr. Sethi and his team decided to investigate this relationship in multiple preclinical models of cancer. To evaluate if cancer-bearing hosts have cancer-promoting microbiota, freshly weaned mice were housed with either genetically engineered adult KPC pancreatic cancer-bearing mice or wild-type cancer-naïve mice. Subsequently, the “guest” mice were given subcutaneous pancreatic ductal adenocarcinoma (PDAC).

In other experiments, wild-type mice had either intact microbiota or were depleted of gut microbiota by oral antibiotics. Both groups were used to model subcutaneous cancers or liver metastases.

The researchers found that mice housed with KPC mice had significantly increased tumor burden compared with mice that were housed with cancer-naïve mice. Depleting gut microbiota dramatically decreased tumor burden in subcutaneous and/or liver-metastasis models of melanoma, PDAC and colon cancer.

Based on the data, Dr. Sethi concluded that:

  • Microbes invade primary and metastatic PDAC
  • Microbes accelerate primary and metastatic PDAC
  • Cancer harnesses antimicrobial immune cells
  • Eradicating microbes potentiates the efficiency of established therapies 

Asked if cancer patients should be put on antibiotics when they are getting chemotherapy, Dr. Sethi said such an approach is “controversial” at this point, but that further study was underway to measure the effect of antibiotics.

The Scientific Forum presentation, Manipulation of the Gut Microbiota Modulates Cancer, was held October 23 at the 2018 Clinical Congress of the American College of Surgeons in Boston. Program, webcast and audio information is available online at facs.org/clincon2018.


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