How Gut Bacteria Could Change Your Response to Renal Cell Carcinoma Treatment

The more scientists learn about gut bacteria, the more fascinating it becomes. It can affect your mood, the foods you crave, and according two new studies, it can even change cancer patients’ response to immunotherapy.

An international team of researchers set out to find links between certain gut microbiome characteristics and the way the body responded to immunotherapy. They specifically looked into the body’s reaction to anti-tumor effects of PD-1 blockade. They examined 100 patients with non-small cell lung cancer or renal cell carcinoma. Renal cell carcinoma is form of kidney cancer which spreads quickly throughout the body. To learn more about this rare condition, click here.

Earlier, the researchers had conducted preliminary experiments. They had tested their theory out by giving mice with these cancers antibiotics, which would clear out their microbiomes. They found that the antibiotics diminished the anti-tumor benefits of anti-PD-1 treatments. They found a similar pattern in patients with kidney, lung, or urothelial cancers. If the patient had recently been prescribed antibiotics before they began immunotherapy, their response rate and overall survival rate showed significant damage.

On the other hand, when the researchers looked at data from patients who had a diverse ecosystem of gut bacteria, those patients had a strong response to anti-PD-1 treatments. They found one bacteria species that kept appearing in patients with a strong, beneficial response, called Akkermansia muciniphila.

The researchers theorized if they boosted the gut microbe ecosystem in a patient, their response would also improve. They tested this out by performing fecal matter transplants from cancer patients who had shown a strong response to immunotherapy to mice who had received antibiotics as well as mice who had been raised in germ-free conditions. They supplemented the fecal matter with bacteria that had been associated with responsiveness, including A. muciniphila. Their findings supported their hypothesis. The fecal matter transplants promoted microbiome diversity, and in turn, immunotherapy response and recovery.

The scientists are still figuring out exactly how this process works. However, they believe it’s clear that the microbiome in a patient’s gut controls their response to immunotherapy.

Another study from University of Texas discovered similar findings in patients with melanoma. This team used RNA sequencing to determine the oral and gut microbiome differences between patients who had or hadn’t responded to immunotherapy. Like the other researchers, they found gut microbes played a big part in response rate. Patients who had a diverse ecosystem generally responded more and fared better. On the other hand, microbes in the mouth didn’t seem to make a huge difference. The researchers went a step further, exploring which specific species benefitted or inhibited response. They found high levels of Faecalibacterium predicted a positive response, whereas Bacteroidales bacteria usually showed up in patients with a poor response.

It’s exciting to have not one, but two new studies that support the same conclusion: if we can learn how to manipulate gut microbiomes, we can make immunotherapy more successful in a greater number of patients than ever before.

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