Sperling Prostate Center

How Gut Bacteria May Undermine Androgen Deprivation Therapy

I was fascinated by a revealing new research study concerning prostate cancer (PCa) and the gut microbiome. Even though the prostate gland and the intestines are both located in the abdominal cavity, nature has ensured that they are separated so dangerous E. coli bacteria in the bowel can’t contaminate the urinary/sexual system. However, there may be indirection interaction between the gut and prostate cancer that we are just starting to learn about.

A brief biology review

First, let me review a little biology regarding a) androgen deprivation therapy (ADT) to treat advanced PCa, and b) the teeny little microbes that inhabit the gut.

  1. We know that PCa is fueled by androgens (male hormones), especially testosterone. Androgens don’t cause PCa, but once it occurs the PCa cells need testosterone to help them grow. Depriving them of androgens puts the brakes on, so PCa growth comes to a halt. This is called Androgen Deprivation Therapy (ADT) and it can be administered by removing the testicles (surgical castration) or administering drugs (chemical castration). Such protocols have harsh side effects because they take away a man’s masculinity. What’s worse is, ADT is not a cure. It buys times, but sooner or later the PCa cells appear to “outsmart” ADT and resume activity. There are many theories, but no one knows exactly why or how it happens. When it does, it’s called castration-resistant prostate cancer (CRPC) because the disease no longer responds to ADT. If the cancer spreads, it’s called metastatic castration resistant prostate cancer (mCRPC).
  2. Digestion in the intestines is an amazing process of utilizing nutrients and getting rid of waste. There is a dedicated nervous system called the enteric nervous system that governs these functions, but there are also helpers in the form of microorganisms, or microbes. These trillions of tiny life forms include bacteria, fungi, and viruses. Collectively, they function as an additional organ. When they are diverse and balanced, they support the immune system, brain wellness, and other health systems while benefiting from being alive in our body. This is called a commensal relationship, meaning a neutral interaction by which neither party causes harm to the other, or gains greater benefit than the other.

How ADT changes the balance

Now, a multicenter European research team has found that changing the balance of male hormones in a PCa patient’s body may actually trigger a response in the gut microbiome that can cause harm to the patient. Pernigoni, et al. (2021) found that when the supply of androgens is switched off through surgical or chemical castration, the gut biome can manufacture androgens that favor the growth and progression of PCa.[i] These natural hormones are absorbed into circulation in the body, giving PCa cells access to them. Thus, the gut microbiome “contributes to endocrine [hormone] resistance in CRPC by providing an alternative source of androgens.”

The research team tested the effects of destroying the microbiome of patients on ADT by administering antibiotics, thus killing the gut bacteria. They found that this delayed the emergence of castration resistance, which reinforced their theory of the microbe activity. While it’s ultimately not a good idea to deplete the gut microbiome, perhaps this finding will offer clues on how to restrain the production of androgens by the microbiome when castration is a necessary therapeutic strategy to stop PCa in its tracks. Much more research will be needed.

The main question is, of course, whether this androgen-making activity of the gut microbiome explains how PCa cells become resistant to ADT. If this is so, it’s not that the PCa cells outsmarted the hormones, as was previously thought. Instead, the gut microbiome is just doing its job of trying to maintain the male hormone balance, yet is unwittingly sabotaging the work of the castration by providing new fuel for the cancer. If true, it’s a very sad irony.

I will be interested to learn if future studies confirm this research, and if this discovery leads to the development of a possible cure for advanced PCa. Whatever the outcome, the sooner we have a potentially curative treatment for advanced PCa, the better.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

[i] Pernigoni N, Zagato E, Calcinotto A, Troiani M et al. Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis. Science. 2021 Oct 8; 374 (6564): 216-24.


About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.

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