Manipulative Microbiomes

Gut bacteria control tumor growth via the mammalian immune system.

By | April 1, 2015

CANCER COMMAND: The microbiome (as puppeteer) affects the immune system’s influence on tumor growth, in tandem with inflammatory cytokines (dogs).ILLUSTRATION BY MELANIE R. RUTKOWSKI AND GRAPHIC DESIGN BY SUBTERRANEAN GRAFIX

EDITOR'S CHOICE IN CELL & MOLECULAR BIOLOGY

The paper
M.R. Rutkowski et al., “Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation,” Cancer Cell, 27:27-40, 2015.

The polymorphism
The gut microbiome influences nonintestinal cancer progression, but the role of toll-like receptor 5 (TLR5), an immune system protein that recognizes commensal bacteria, was a mystery. As more than seven percent of people have nonfunctional TLR5, José Conejo-Garcia of the Wistar Institute in Philadelphia and colleagues explored how TLR5 impacts tumor growth.

The controller
In a mouse model of sarcoma, the researchers found that tumors grew much faster in wild-type mice than in TLR5-deficient ones. Wiping out the mice’s microbiomes diminished the disparity, indicating that TLR5’s tumor-promoting effects are driven by commensal bacteria. TLR5-dependent signaling triggered the production of inflammatory interleukin 6 (IL-6), which in turn activated an immunosuppressive cascade—not switched on in TLR5-deficient animals—that promoted tumor growth.

The twist
In human breast cancers or mouse mammary carcinomas, where IL-6 levels are much lower, TLR5 had the opposite effect. Tumors in TLR5-deficient mice grew better, due to the upregulation of IL-17, a different inflammatory cytokine. As in the sarcoma model, any differences between TLR5-deficient and wild-type mice disappeared upon antibiotic treatment. “Cancer is a systemic disease that is very dramatically influenced by commensal bacteria,” Conejo-Garcia says.

The manipulation
“It’s very exciting to see this kind of progress,” says Susan Erdman of MIT. She says looking into the effects of human polymorphisms such as TLR5 “really contributes to the concept of personalized medicine in cancer therapy.” As a first step toward future treatments, study coauthor Melanie Rutkowski is exploring how manipulating the microbiome could inhibit tumor growth.

Add a Comment

Avatar of: You

You

Processing...
Processing...

Sign In with your LabX Media Group Passport to leave a comment

Not a member? Register Now!

LabX Media Group Passport Logo

Comments

April 14, 2015

Keep it simple.

The most efficient system is to rebalance the composition of the bacteria in the microbiome on a natural way. We don't need to fight something that doesn't exist anymore do we?

Of course I forgot that this approach will not bring a patent and the big money but I tought it was about health. My mistake if this is not the topic.

 

Avatar of: Paul R Walsh

Paul R Walsh

Posts: 8

April 14, 2015

As 'Prof Guy Van Elsacker' said, “this approach will not bring a patent and the big money…

Corporations are unlikely to develop treatments to correct imbalances in the human microbiome without a profit incentive.  So, unless we find a method to incentivize such treatments, progress in this area will require funding from the Federal Government or grants from philanthropic entities such as the Gates Foundation or the Kroc Foundation.   

Avatar of: Bombshell

Bombshell

Posts: 2

Replied to a comment from Prof. Dr. Guy Van Elsacker made on April 14, 2015

April 19, 2015

I agree with you!! Most diseases start in the gut!

Popular Now

  1. Publishers’ Legal Action Advances Against Sci-Hub
  2. Decoding the Tripping Brain
  3. Metabolomics Data Under Scrutiny
    Daily News Metabolomics Data Under Scrutiny

    Out of 25,000 features originally detected by metabolic profiling of E. coli, fewer than 1,000 represent unique metabolites, a study finds.

  4. Do Microbes Trigger Alzheimer’s Disease?
AAAS