If you’ve ever come down with a fever, a festering cut, or a particularly nasty case of strep throat, more often than not, your health care provider will have you popping antibiotics for a couple of days. Once you get better, you think nothing of it — except your gut does.
According to a study presented this month at a meeting of the American Society for Bone and Mineral Research, the researchers found that for melanoma — a serious form of skin cancer that can spread to other organs — taking broad-spectrum antibiotics may accelerate its growth by disrupting the gut microbiome and its influence over the immune system, particularly two types of immune cells called natural killer (NK) and helper T (Th1) cells. This research points to a growing body of evidence that aggravating our gut bugs — whether through antibiotics, other medications, or lifestyle choices such as diet — is not beneficial for our overall health and well-being.
Here’s the background — A popularized depiction or notion of cancer is that it’s ruthless, stubborn, and hard to beat and that without medical intervention, we’re utterly defenseless. While that’s not unfounded, our bodies are, to some extent, equipped to fight these renegade, mutated cells.
The immune system is constantly surveilling the body not just for pathogens in the form of viruses or bacteria but anything programmed to do harm, like cancer. A class of white blood cells called T cells can stake out cancer either head-on or by organizing a hunting party, of sorts (Th1 cells are involved in the latter).
NK cells, too, play a huge role in being the first line of defense against tumor development, Manoj Chelvanambi, a postdoctoral fellow in surgical oncology at the University of Texas MD Anderson Cancer Center, tells Inverse.
“It’s very well-established if you knock out NK cells, tumors just take off and grow extremely fast,” explains Chelvanambi, who wasn’t involved in the study.
But cancer cells have an arsenal of evasive maneuvers up their sleeve, like usurping immune cells and reprogramming them or wrapping themselves up in some stealthy camouflage. These tactics make it difficult to eliminate a tumor without outside help, but that’s where the gut microbiome can swoop in, Nadim Ajami, director of scientific research for MD Anderson’s Program for Innovative Microbiome and Translational Research, tells Inverse.
“We also know that one of the functions of the microbiome [what] I call it the immune’s system sparring partner. It’s like a trainer for the immune system,” says Ajami, who also wasn’t involved in the study.
Studies show the gut microbiome may boost the effectiveness of cancer treatments or mitigate the severe side effects of immunotherapy through fecal microbial transplants. On the flip side, when the delicate balance or homeostasis of good and bad bacteria is thrown into disarray — called dysbiosis — this promotes harmful microbes that encourage cancer growth.
How they did it — Gut microbiome research is still relatively uncharted territory. So what researchers at Emory University, who conducted the new study, wanted to understand was how this vast microbial ecosystem influences tumor growth in bones, something that can happen in aggressive melanoma, breast, prostate, and many other types of cancer, Subhashis Pal, a postdoctoral fellow at Emory University and the paper’s first author, tells Inverse.
“Bone metastases are a common situation where cancer [spreads] to the bone, and we wanted to explore the possibility that our gut microbiome could regulate the process,” says Pal. “We started exploring all these angles like if we deplete the gut microbiome or create gut dysbiosis condition by using antibiotics, how does that affect tumor growth?”
To do that, Pal and his colleagues took 12-week-old mice and had them drink a cocktail of broad-spectrum antibiotics-laced water (which included ampicillin, vancomycin, neomycin sulfate, and metronidazole) for two weeks. They then injected melanoma cells — derived from mice and genetically engineered with a bioluminescent protein (meaning cancer lights up on imaging) — into the hearts of some of the mice and bones of others. Broad-spectrum antibiotics were again given for another week for a total of three weeks.
To confirm whatever effects they were seeing were strictly associated with the gut microbiome and nowhere else, the Emory researchers had another group of 12-week-old mice drinking water containing two antibiotics that work locally in the gut and aren’t absorbed into the rest of the body — neomycin and bacitracin — for two weeks before injecting melanoma in their mousey hearts and bone. (There was also a control group of mice that drank plain old, antibiotic-free water.)
What they found — The researchers discovered that with prolonged broad-spectrum antibiotic use muddling up the mice’s gut microbiomes, the number of NK and Th1 cells was depleted compared to mice who didn’t get antibiotics.
“The [number of these] cells really goes down, particularly in gut-associated lymphoid tissues,” says Pal. “The mice’s tumor defense was really weakened, and ultimately, we [saw] bigger tumor growth.”
That sounds interesting, you might be thinking to yourself, but what connection do immune cells in the gut have with the bone?
Pal and his team saw in the antibiotic-free mice, there was a spike in the number of NK and Th1 cells in the bone marrow that wasn’t present in the antibiotic-fed mice. This indicated that in response to melanoma making itself at home where it’s not wanted, the gut microbiome was recruiting and shipping off immune cells to fight in the bone marrow. The researchers found further evidence for this when they discovered well-known immune proteins called CXCL9 and CXCR3 being secreted by bone marrow cells, seemingly beckoning NK and Th1 cells to come hither.
Digging into the details — These findings are just the tip of the microbiome-immune system iceberg, says Pal, Chelvanambi, and Ajami. There’s a lot more to suss out before we can say whether what’s observed in mice will necessarily be the same in humans or in other cancers, not to mention if there are other immune cells or proteins involved.
“A more detailed clinical study or using human stool samples or humanized mice would be more beneficial,” says Pal. “We are doing those, but we’re still in the preliminary stages.”
Why it matters — Broad-spectrum antibiotics are often a cornerstone of medical treatment for many cancer patients since therapies like radiation or chemotherapy render the immune system weakened, making patients more susceptible and at a high risk of catching bacterial and other infections.
How long an individual needs to be on antibiotics can depend on their type of cancer, says Jonathan Peled, a medical oncologist at Memorial Sloan Kettering Cancer Center, who was not involved in the study. For cancer easily treated with surgery, patients only need to be on antibiotics for a short duration, typically before surgery. Medium exposure would be when a patient undergoing chemotherapy for breast or lung cancer develops a fever and infection due to low blood counts; to treat the infection, doctors use a week-long course of antibiotics.
“At the most intense end of things [with] patients I have taken care of… are maybe some hematological malignancies where we’re getting treatments like bone marrow transplantation,” says Peled. “Those patients sometimes get weeks of very broad-spectrum antibiotics, they have prolonged hospitalizations for nutritional disturbances, and all of this is accompanied by dramatic perturbations of microbiome composition that are essentially unlike any microbiome perturbations seen in any setting in humans.”
As you can imagine, then, if broad-spectrum antibiotics carry a risk of causing cancer, we wouldn’t want these life-saving drugs to be part of the problem. Peled says in recent years, with a better understanding of the gut microbiome, clinicians have been reassessing when antibiotics should be used and how to minimize microbial collateral damage.
“[These findings] add to the sentiment that we in clinical practice should always be judicious in our use of antibiotics, and to use the most narrowly-targeted antibiotics that are appropriate for that clinical situation for the shortest period of time,” he says.
The fact it’s prolonged antibiotic use that’s worrisome needs to be kept in mind (these drugs are still our best bet against pathogenic bacteria). In recent years, studies from a group of hospitals in the U.S. and another from Umeå University in Sweden examining the association between antibiotics and colorectal cancer found that popping the bacterial killers for too long (two months or more in the U.S. study, six months or more in the Swedish study) led to an increased cancer risk in the women studied, most likely through gut dysbiosis.
What’s next — While this study continues to prop up the immense promise and potential of the microbiome, there’s a long road ahead before going from lab bench to clinic, Golnaz Morad, a postdoctoral research fellow in surgical oncology also at MD Anderson Cancer Center and not involved in the study, tells Inverse.
“We have to really focus on the components that are involved in the clinic in these [cancer] patients, especially as bone metastasis is usually a late event,” says Morad. “So the question is how do all these previous treatments affect the microbiome and how is the current treatment [patients] are receiving [affecting] the microbiome, besides all the usual lifestyle and other factors.”
Going forward, Pal and his colleagues at Emory at hoping to see what they’ve uncovered in mice tracks with the human gut microbiome and with other malignancies like breast cancer. A more long-term research plan in the next couple of years is to investigate how diet impacts the microbiome and whether we can improve our chances of fighting cancer by switching up what we pile on our plates.
Fine, cancer-free dining, indeed.
