Why do some therapies work wonders on some patients, but seem to have virtually no effect on others? Two fascinating new studies in Science shed light on one potential contributing factor in treatment outcome for cancer patients: The trillions of microrganisms that live in our guts.
The makeup of a person's microbiome, the two studies found, may play a significant role in whether cancer immunotherapy is effective. A diverse microbiome populated with a lot of good gut bacteria can help maximise the effectiveness of immunotherapy treatments, one paper found. Meanwhile, the other found that antibiotics which deplete the body of its microbial diversity seem to make treatment less effective.
The two new studies add to a growing body of evidence that suggests gut bacteria plays an important role in disease. In one intriguing study published earlier this year, researchers traced the roots of a brain disorder that had long stumped scientists to a particular type of gut bacteria. Other studies have linked gut bacteria to everything from athleticism to anxiety, although some of those results are sometimes controversial.
Recently, several other studies have shed light on just how important having the right cocktail of gut microbes may be in treating cancer in particular. Another study published this week found that the presences of certain gut bacteria could cause some chemotherapy treatments to become toxic to patients with colorectal cancer.
"Many studies across the field of microbiome research have clearly established that our gut microbes can dictate how our immune system functions throughout our body," Justin Sonnenburg, a Stanford microbiologist not affiliated with the two new Science studies, told Gizmodo. "This gut microbiome-immune connection means that changing the gut microbiome, whether via diet, probiotics, antibiotics, faecal transplant, or using some other means, has the potential to influence diverse processes, such as autoimmune disease, response to infections, and effectiveness of immunotherapy."
One of this week's Science studies looked specifically at two bacteria that seem to bolster the efficacy of an immunotherapy drug for metastatic melanomas that targets a checkpoint protein on immune cells known as PD-1. Researchers collected oral, gut and faecal microbiome samples before and after therapy in cancer patients. They then divided the study group into patients that had responded to therapy, and those that had not, genetically sequencing the microbiome of patients in each group to look for commonalities. Two particular bacteria, faecalibacterium and clostridiales, seemed to account for the difference in the number of cancer-attacking T-cells that each patient group had. In a second part of the study, when researchers gave faecal matter transplants from patients that responded well to mice with microbe-free guts, they also responded positively to treatment.
The second study also looked at the efficacy of PD-1 inhibitor immunotherapy, but in patients with kidney and lung cancer. It found patients who had recently undergone a course of antibiotics had poorer survival rates. Those antibiotics appeared to be linked to a depletion of a bacterium called Akkermansia muciniphila in the microbiome. Again, researchers implanted the bacteria into germ-free mice and found it increased their immune response during treatment.
The two studies point to a potentially powerful method for improving the outcome of cancer treatment: Examining patient microbiomes to make sure they have the necessary flora for treatment to work.
It also points to a need for more research to better understand the connections between our gut health and the rest of our health.
"What is urgently important," said Sonnenburg, "is to conduct detailed study of these connections in humans so that we can begin to harness this newly appreciated potential for improved human health."