Prostate cancer and the microbiome

The human gut is stuffed full of microbes, many of them essential for our health, but new research suggests that they can also undermine the effectiveness of some treatments for prostate cancer. Prostate cancer is a very common condition, but it can often be controlled, at least for a while, with drugs to block the production of the male hormone testosterone, which acts as a growth signal for the cancer. But, in some patients, this treatment stops working, and a new study suggests this might be because their gut microbes start to make testosterone-like signals instead. Vincent Gnanapragasam took Eva Higginbotham through it - he wasn’t involved in the study but is a urologist specialising in prostate cancer at Cambridge University...

Vincent - So actually this idea that the gut microbiota may contribute to prostate cancer has been around for a little while, but in this study, what they did was to really go into the details of how this might be possible. So in effect, what they did was they studied mice and they looked at the microbiota or the organisms that grow in the bowels of these mice, in different models with and without treatment with androgen deprivation, which is to say, to block the male hormone. And what they found was that these bacteria within the gut could actually make some of the male hormones, or at least some of the precursors of the male hormones. And by changing that microbiota, you could actually alter how much male hormones that they produce in a situation where you wouldn't expect it to find particularly where the male hormones had been ablated or blocked by other means. They went further to show that you could identify specific bacteria, which is present, might predict that these mice and actually in patients as well, they might do better or worse from the treatment. So they came up with something they called bacterial fingerprints. And this work is obviously at a very early stage, but this provides a very interesting idea about how perhaps antibiotic treatments and things like that may be useful, particularly in advanced stages of disease.

Eva - Do we know why a bacterium or bacteria might make testosterone like signals in the first place? Does it play some role for them too?

Vincent - That's a very good question. And of course it's sort of counterintuitive to think about single cell organisms being able to biosynthesize or make these complex molecules. And I suspect that it's got to do with an underlying enzymatic reaction, which wasn't supposed to do that. But of course we have evolved over generations and thousands of years to live with these organisms. In many ways, we are a symbiosis of different organisms together with ourselves and diet comes into why people need to have different types of organisms. So I don't think we quite know why these specific organisms do this in terms of what's beneficial to them. And that is not what they address within this study, but it's clear that somehow these organisms have grown to live within us to produce these things, which obviously we didn't know about until, until we looked for it.

Eva - And what is it about having testosterone that prevents the treatment from working?

Vincent - So in this particular study, they looked at patients who were really in a sense gone through the standard therapies and failed and where castration or the blocking of the male hormones is the only therapy that's really viable. And the idea is by using drugs or surgery is to remove the male testosterone that causes prostate cancer to shrink, but something which has been come into the awareness of urologists and oncologists for many years is that there seems to be a basal level produced by other mechanisms, which were bypassing the so-called standard castration. So in fact, at one time we used to call it hormone refractory, and now we call it castrate refractory, which means to say that there are mechanisms producing these androgens despite the standard treatment. And it's these low levels of androgens, which seem to be still driving the prostate cancer, even when we think the conventional mechanisms should be working and that we found was happening with things from the adrenal glands. And so we found drugs to try to target that. And now this, this research, and in fact, previous research has suggested that even the bugs within our gut can also produce this.

Eva - Then just very briefly, does that mean then that we might give antibiotics to people with prostate cancer who don't seem to be responding to the treatment?

Vincent - I think it's an idea. It's a possibility. This is very early stage research, but certainly a promising avenue to investigate in the future.