Prostate Cancer

How Gut Bacteria Undermine Prostate Cancer Treatment

The evidence here is strong for a recent finding, combining human samples with several independent animal models. Prostate cancer grows in response to androgens, the male sex hormones. The main treatment for advanced disease works by cutting those hormones off. It works well, until it stops. Why it stops has been one of the field's central questions, and part of the answer turned out to be in the intestine.

A treatment that removes a fuel supply

Androgen deprivation therapy lowers testosterone to very low levels, either with drugs or surgically.

Prostate tumours deprived of that fuel shrink, often dramatically. For a period, the disease is controlled.

Then it returns and keeps growing despite testosterone remaining suppressed. That stage is called castration-resistant prostate cancer, and it accounts for most deaths from the disease.

Various explanations have been proposed, mostly concerning changes inside the tumour itself. Researchers asked a different question. If the tumour is still finding androgens, where are they coming from?

Bacteria that manufacture hormones

The answer was that some gut bacteria make androgens themselves.

Certain species can convert androgen precursors, meaning inactive building-block molecules circulating in the body, into active testosterone and related hormones. They use an enzymatic step resembling the one human cells use.

Researchers found that starting hormone therapy expands exactly these species. Both in mice and in patients, androgen deprivation was followed by the growth of bacterial populations capable of producing the hormone the treatment was designed to remove.

Species including Ruminococcus were enriched in patients whose disease had become resistant.

So the treatment appears to create conditions favouring bacteria that undo part of its effect.

Source: Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis

Removing and transferring the bacteria

Two experiments turned that observation into something stronger.

First, researchers wiped out gut bacteria in tumour-bearing mice using broad-spectrum antibiotics. Resistance to hormone therapy was delayed and survival improved. This was repeated across four different mouse models of prostate cancer, including two using human tumour tissue.

It also worked in mice lacking a functioning immune system, which rules out the effect being purely immune-mediated and points at the hormones themselves.

Second, they transplanted stool. Mice receiving bacteria from resistant mice or from resistant patients became resistant to hormone therapy.

Mice receiving bacteria from patients whose cancer still responded to treatment had their tumour growth controlled. So did giving a single species, Prevotella stercorea.

Same tumour, same treatment, different bacteria, different outcome.

Source: Intestinal microbiota drive CRPC

What this changes and what it doesn't

Some care is needed with how far this is taken.

This is about resistance to treatment in advanced disease, not about whether gut bacteria cause prostate cancer. Those are different questions and this work addresses the first.

Nobody is treating patients this way. Antibiotics carry their own risks and would flatten beneficial bacteria alongside the androgen producers. Stool transplants for this purpose remain experimental.

What it does change is the framing. The bacterial community becomes something that can be measured to identify men at high risk of resistance, and potentially something to modify rather than an irrelevance.

Diet is the obvious lever, since it's the main thing shaping which bacteria dominate, though no trial has yet tested dietary change against treatment resistance.

What this means for you

Prostate cancer needs specialist care, and treatment decisions from screening through to hormone therapy should be made with a urologist or oncologist. In addition, the research above found gut bacteria manufacturing the hormones that hormone therapy is designed to remove, with clearing those bacteria delaying resistance across four mouse models and transplants transferring resistance between animals. A varied, plant-rich diet supports the same gut bacteria this research ties to a community less dominated by the androgen-producing species. That's the same idea behind GutLab, everyday gut health starts with regularly feeding the microbiome a broad range of plant-rich ingredients.