Gut Microbiome Plays a Role in How Prostate Cancer Patients Respond to Oral Therapies

Bacteria in the gut may play a role in the treatment outcomes of patients with prostate cancer taking oral medications, according to a study published in Nature Communications.

The results from the study showed that since the drug abiraterone acetate is metabolized by bacteria in the gut that help to both reduce harmful organisms and promote helpful ones, the authors suspect that the microbiome influences patients’ responses to medications.

"Research is beginning to uncover the ways in which the human microbiome influences cancer development, progression, and treatment," said Brendan Daisley, a PhD candidate at Western's Schulich School of Medicine & Dentistry who is conducting research at Lawson, in a press release. "Our study highlights a key interaction between a cancer drug and the gut microbiome that results in beneficial organisms with anti-cancer properties."

Traditionally, therapies for prostate cancer are designed to deprive the body of hormones called androgens in order to stop cancer growth.

"Unfortunately, traditional androgen deprivation therapies are not always effective," said Joseph Chin, PhD, Lawson associate scientist, professor at Schulich Medicine & Dentistry, and urologist at London Health Sciences Centre (LHSC), in a press release. "In those cases, alternative therapies are explored."

Abiraterone acetate has been used to treat prostate cancer after patients develop resistance to other treatments. Although abiraterone acetate reduces the presence of androgens, it functions through a different mechanism and must be taken orally.

"When drugs are taken orally, they make their way through the intestinal tract where they come into contact with billions of microorganisms," said study lead researcher Jeremy Burton, PhD, Lawson scientist, associate professor at Schulich Medicine & Dentistry, in a press release. "While it's long been a mystery why abiraterone acetate is so effective, our team wondered if the gut microbiome plays a role."

The study participants included 68 patients with prostate cancer from LHSC, including those being treated with abiraterone acetate and those being treated with traditional androgen deprivation therapies.

Following analyses of patient stool samples, the authors found that patients' gut microbiomes changed drastically after treatment with abiraterone acetate.

After metabolizing the drug, there was an increase in the presence of a gut bacterium called Akkermansia muciniphila. This bacterium is referred to as a “next-generation probiotic” and has been investigated in several large cancer studies.

In these studies, the bacterium has been shown to support a better response to cancer immunotherapy drugs. Additionally, the bacterium can result in other positive health benefits, such as an increased production of vitamin K2, which is known for anti-cancer properties that can inhibit tumor growth, according to the authors of the current study.

The researchers also observed that both abiraterone acetate and traditional androgen deprivation therapies caused organisms that use androgen to decrease in the microbiome as well.

"These findings clearly demonstrate that the gut microbiome is playing a role in treatment response," Burton said.

The researchers explained that they are also interested in investigating the effects of microbiome on treatment outcomes for a variety of other diseases. For example, they plan to assess whether fecal microbiota transplants from a healthy donor can increase organisms such as Akkermansia muciniphila and improve response to immunotherapy in patients with melanoma.

Furthermore, they plan to study whether a patient's microbiome can be a predictor for responses to specific therapies.

"While more research is needed, we may one day be able to analyze a patient's microbiome to determine the best course of treatment or even influence the microbiome to improve outcomes," Burton said in a press release. "This could lead to a new frontier in personalized medicine."

REFERENCE

Gut microbiome may influence how cancer patients respond to oral therapies, study suggests. London, Ontario: Lawson Health Research Institute; September 29, 2020. eurekalert.org/pub_releases/2020-09/lhri-gmm092920.php. Accessed October 6, 2020.