November 20, 2017 2 comments

How our gut bacteria can fight tumor growth

Gut Microbiome

The average adult gut extends over 20 feet and is the home of over a thousand different bacteria species, all with specific roles to play in digestion. In fact, science is just starting to understand how important the microbiome is to our health, with animal studies even showing the potential for certain strains of bacteria to inhibit the growth of tumors. Before we delve deeper into the specifics of those studies, first some background on this emerging field of science.

Microbiome research is brand new

Scientists have only taken note of your gut bacteria recently, thanks to the over two decades worth of effort from Jeffrey I. Gordon, MD, the father of the field and one of the most influential scientists researching the human microbiome today.

The microbiome plays a role in a vast array of diseases

By studying the bacteria that resides in the gut, Gordon and his team have shed light on how the tens of trillions of microbes work to aid in the fight against obesity (R), cardiovascular disease (R), autoimmune disease (R), cancer (R) and even regulate our emotional behavior (R).

Early microbiome development is essential

The healthy development of your microbiota is pivotal in growth and development, and when your microbes aren’t healthy your gut doesn’t work as well, which can lead to chronic health problems. 

One of the major discoveries Gordon’s lab made was that once they had been weaned from their mothers, mice raised in germ-free conditions (who don’t have a microbiome) would stop producing  α1,2-linked fucosylated glycoconjugates in the ileal epithelium (the final section of the small intestine in mammals), while the conventionally raised mice would maintain this production throughout life.  

In case you’re wondering, Glycoconjugates are complex carbohydrates that can serve as information carriers, allowing cells to communicate with their surroundings, helping developing cells move to the right location, blood clotting, immune responses, wound healing, and other cellular processes. In normal mice, and humans, bacteria add fucose sugars to the carbohydrate in a process called fucosylation, which then allows for the carbohydrate to be turned into a nutrient source for the bacteria. Gordon and Bry found that the microbiota was required in order to complete the fucosylation program.

Astonishingly, the germ-free mice would regain the fucosylation program if they were exposed to gut microbiota from the conventional mice. Lynn Bry, who trained under Gordon, achieved this by colonizing the germ-free mice with Bacteroides thetaiotaomicron, a bacteria that normally occurs in the small intestine of healthy adults, and mice, that scavenges a variety of carbohydrates, including L-fucose, from more complex host and dietary glycoconjugates. Bry found that inoculation with B. thetaiotaomicron  induced a normal pattern of ileal fucosylation within 5 to 7 days.  “We felt that this dynamic of nutrient sharing was an extremely important foundation for establishing and maintaining mutually beneficial relationships between members of the ­microbiota and their host,” Gordon said.

See also: 8 ways to rebuild your gut health without probiotics

The microbiome and tumor growth

Building on this research, Thomas Gajewski, an immunologist at the University of Chicago in Illinois, identified the microbiome as a key player in tumor growth.

When he observed that mice from different suppliers had different rates of melanoma tumor growths, Gajewski decided to co-house the animals and found that the disparity in growth rates disappeared when the communities were combined. Noting that rodents will often eat fecal matter of their co-habitants, he decided to sequence ribosomal RNA of the gut bacteria of the mice. Using Gordon’s bacteria genomics library, Gajewski and his team identified Bifidobacterium, one of the bacteria found in the gut of Jackson mice, as the cause of the changes in tumor growth.  

Probiotics slowed tumor growth in mice

The scientists next fed the fast-growing tumor mice from Taconic Farms a commercially available probiotic cocktail of Bifidobacterium species, which included B. breve and B. longum, and found that the groups receiving the probiotic had better control of tumor growth as compared to their non-treated counterparts (Sivan, et al, 2015). This groundbreaking study found that the immune system’s ability to combat tumors was highly influenced by gut bacteria. Remarkably, the strains of Bifidobacterium used in the study are commonly sold at supplement stores across the country. Now, efforts are focused on identifying ways to add complementary probiotics as a novel way to help cancer patients.

“There is a window in human postnatal ­development of the microbial organ that we may be able to modify in ways that promote ­long-term health,” says Gordon, but his work extends beyond the lab. He sees the human-bacteria partnership as a new way to approach well-being both in local communities and in big agriculture. “We need to consider not only the biological implications, but also the ­societal issues raised by these efforts.”

Jennifer Nguyen

Jennifer Nguyen is a scientist living in San Diego. She did her training in molecular immunology, with a focus on checkpoint proteins and their role in autoimmune disease. She now works in cancer immunology, and spends her time away from the lab hanging out with her dog, climbing, and practicing yoga.

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2 Comments

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    • Jennifer Nguyen says:

      Hi John,

      That’s a great question. Thomas Gajewski’s work on the microbiome and cancer is groundbreaking. We’ve started to look at how the microbiome can be harnessed to help make our immune-modulators more effective at treating cancer patients. It also helps us understand why some patients respond better to immunotherapies and how we can overcome that. This also lead us to look at differences in microbiomes in the autoimmune space (like for Multiple Sclerosis, IBD, and even Psoriasis) between different genotypyes.

      -Jennifer

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