Read the Full Video Transcript

Alicia Morgans: Hi. I'm so excited to be here today with Professor Robert Thomas, who is joining me from Addenbrooke's and Bedford, Cambridge University Hospitals in the UK, where he's coming to talk at GU ASCO 2025 about the gut microbiome and how it relates to prostate cancer. Thank you so much for being here with me today.

Robert Thomas: Thank you for inviting me.

Alicia Morgans: Can you tell us a little bit about the gut microbiome and what this prostate cancer connection is as you set us up to understand your study?

Robert Thomas: Well, I believe that the gut microbiome has been sort of overlooked by the health profession for years. We know that people who have poor gut health are more likely to feel tired, have poor cognitive function. There's an increased risk of chronic degenerative diseases such as arthritis, dementia, but also cancer, not only in the gut but elsewhere in the body, including prostate.

But what we don't know is, can we do interventions to improve the gut and actually improve your outcomes? Well, in terms of treatment, there are some studies that say that if you have better gut health, you respond better to the biological agents we're using more and more now, such as PD-L1 inhibitors, and there are fewer side effects.

So we sat down with three patient support groups in Britain with probably over about 1,000 patients with prostate cancer and said, look, we know gut health is important, and we want to design a study. And they helped us very much with the design of this, which we're very grateful for, which was partly due to the success. We recruited 220 men in less than six months, which is amazing.

So what we wanted to do is combine two nutritional interventions, which had what we call phytochemical-rich foods, such as the things in tomatoes, colorful broccoli, things like that, and combine that with selected prebiotics with the aim to improve gut health and see if that improves their well-being. And that was a hypothesis for the study.

Alicia Morgans: Wonderful. Can you tell us, before we get into the outcomes, is it possible to really change the gut microbiome, and how effective is that with these prebiotics that you've talked about?

Robert Thomas: Yeah, the gut microbiome is a very dynamic organ. As you know, there are trillions of different healthy bacteria. In fact, there's probably more genetic material from our microbiome than in our own cells. So it's not a surprise it really affects us. And things alter it in a negative way, like having too much sugar, not exercising, taking some antibiotics, or being stressed.

But there are things which alter it in a very positive way. And one of the things is to eat lots of phytochemical-rich foods, as I said, things like broccoli, mushrooms, et cetera, because these act as prebiotics and help to enhance, for want of a better word, the friendly bacteria in the gut.

There's also evidence that you should be having more bacteria-rich foods, such as fermented foods, kimchi, kefir, kombucha, that sort of thing. And certainly in the British diet, we're quite deficient in those. We don't really eat a lot of that.

So, yes, we know—there are lots of data—almost on a day-to-day basis, the microbiome is changing. And you can certainly enhance it with interventions. And we'll come on to that for the study, as well.

Alicia Morgans: Wonderful. So tell me, what did you find in the study?

Robert Thomas: To go back a little bit, what we did, we gave every man a phytochemical-rich capsule. So it had six different foods, which were selected based on previous evidence of some effect. And so they all started with that. And then we randomized, in a double-blind fashion, a five-blend lactobacillus probiotic, which had things like inulin and a bit of vitamin D, which also acts as a prebiotic, actually.

So what we looked at was the PSA in the four months before baseline and then four months afterwards. And most men in the study had Cambridge Prognostic Group 1 or 2, so low-risk disease, effectively. But most were actually progressing. So we were referred from our urological colleagues patients who were thinking they may need to leave active surveillance. So it's a different group than perhaps your average active surveillance.

So the doubling time pre-entry was about 19 months. And after trial entry it extended threefold to 64 months. So there was a very significant slowing, on average, of PSA. We then looked at the two groups, the randomized groups who had the probiotics or not. And that was where this is, I think, a world first.

So it's never been actually shown that if you intervene with a probiotic, you get a further reduction in PSA progression. In fact, in the group that had the probiotics and the phytochemicals, the PSA fell significantly. And the difference in PSA progression, therefore, between the two randomized groups was about 28%, which was highly statistically significant.

Alicia Morgans: And all they really had to do was take those probiotics.

Robert Thomas: They took two capsules, one which was what we call a phytochemical-rich food capsule, and that had—

Alicia Morgans: But that was the prebiotic that everyone took, or was this—

Robert Thomas: Everyone took that, yeah. So everyone took a phytochemical-rich food, which had broccoli, green tea, turmeric, pomegranate, cranberry, and ginger. And they act as prebiotics, but they also have other benefits. We know they're anti-inflammatory. They enhance antioxidant pathways, et cetera. And then they were randomized to the probiotics, the actual bacteria, the healthy bacteria.

Alicia Morgans: But then the group that had the most prolongation, all they had to do was add that extra probiotic. And what did that look like on a daily consumption basis?

Robert Thomas: Basically, it was just two capsules of both, and they just took it with their meals, which was very well tolerated. We had about 6% say they got a bit of initial bloating, which is common if you take probiotics. But more patients said they felt better.

But as well as PSA, which was great to see—and the men were very encouraged by this—for the first time, we actually showed that there was a reduction in urinary symptoms. So there was about a 25% improvement in urinary symptoms, such as getting up at night or urgency. And there was a small benefit in erectile dysfunction, as well. And that just goes to show that the overall well-being of men in the study was being improved by this. So it's nice to have a natural intervention which actually improves well-being. I'm not saying we do this instead of drugs, but most of the drugs we give have side effects, and it doesn't improve well-being. But that's the advantage of doing lifestyle nutritional interventions.

Alicia Morgans: Very, very interesting. Do you have any information on whether there was a difference between the groups in terms of their receipt of definitive therapy? Since you said that they were essentially an active surveillance group that was coming up on perhaps needing definitive therapy.

Robert Thomas: So most of the men in the study were actually progressing at trial entry, with a PSA doubling time of about 19 months. So they were already thinking of leaving active surveillance before they started.

Now, in the actual phytochemical-rich supplement and probiotic group, the PSA actually fell. And this was supported by MRI changes, which showed no change. So it was very clear to me that this would persuade more men to stay on active surveillance. Nevertheless, we put this back to the patient support group, and they unanimously agreed that that would be reassuring to them. But in terms of actual hard data, at the end of the four months, there were eight patients who actually opted for radiotherapy or surgery in the placebo group, and there was one in the intervention group.

Now, as a scientific committee, we decided not to actually analyze that statistically because we feel it's a bit early. It was only a four-month intervention. So men have been given the supplements now—both supplements to take—and we're going to look in to see if there's any actual objective changes in their choices six months to a year down the line, which we think is a much more accurate reflection of what's going on.

So what that means for us as doctors and patients is that more men are going to stay on active surveillance, avoiding the toxicity of, say, radiotherapy or surgery or even hormones in some cases, and even possibly saving money for the NHS or other health providers.

Alicia Morgans: That's wonderful. And my final question is really around those symptoms that I think are probably patient-reported symptoms, erectile function and some others. Was there a difference between the groups, or was that, within the entire study, those things changed from baseline?

Robert Thomas: Well, we looked at them four months before and at baseline and asked after. And for the symptoms, we did the whole group, actually. So there was definitely about a 25% improvement in symptoms from baseline to the end of the study. We didn't actually look to see if there was any difference between the two groups. So that's maybe something we should be looking at.

Alicia Morgans: OK, wonderful. So if you had a final message to tell viewers—because some of these things are probably lifestyle interventions that are available to individuals, people to clinicians, right now—what would your message be?

Robert Thomas: Well, men are very interested in self-help strategies. We know that over 75% take a supplement of some sort, but they do crave having robust data such as this in a double-blind randomized trial. So I think this trial very clearly says we should be advising men—or they'll find out the results themselves—to take lots of phytochemical-rich food, lots of herbs, spices, colorful foods. And if they want to take a supplement, we now know there's evidence for certain types. And there are lots of supplements out there that have no evidence.

It also, for the first time, shows that gut health is also very important, not just to make you feel better and give you more energy, but actually to slow down the rate of your prostate cancer progression. So eat your kimchi. Drink your kefir. Stop having so much processed sugar. Exercise. These things really matter for your gut health, and it will slow down the rate of progression.

Alicia Morgans: Well, that's so exciting, so interesting that there was a longer time to that PSA rise and certainly encouraging for people who are on active surveillance to continue that process, but also consider these lifestyle interventions as something that might really make a difference in their long-term follow-up. Thank you so much for your time and for your expertise.

Robert Thomas: Thank you.