How The Microbiome Can Affect Cancer Treatments

IRA FLATOW: This is Science Friday. I’m Ira Flatow. Later in the hour, we’ll talk about whether the Supreme Court may be allergic to math. But first, we are starting to understand that our microbiome, the trillions of bacteria, viruses, fungi in our gut has a far reaching influence way beyond just our digestive system. It’s been called our second brain. There’s almost uncountable unseen microbes. These almost uncountable unseen microbes can affect our mood, our physical health, even our risk of disease. And scientists are investigating how this mix of microbes interacts with one of the most complicated diseases. I’m talking about cancer, and what this might mean for treatments.

A group of researchers looked at how the bacteria in the body of melanoma patients affected their treatments, and the results were published this week in the journal Science. Let me introduce my guest. Jennifer Wargo is an author on that study. She’s also professor of surgical oncology and genomic medicine at the University of Texas M.D. Anderson Cancer Center in Houston. Welcome to Science Friday.

JENNIFER WARGO: Thank you so much, Ira.

IRA FLATOW: You’re welcome. In your study, you compared the microbiome of melanoma patients that were and were not responding well to immunotherapy. And what did you find?

JENNIFER WARGO: Yes, that’s correct. And you know, Ira, so we actually had known about some science that was published a few years ago that showed in mice that if you look at the bacteria in the mice, and you can actually see differences between mice that respond or don’t respond to immunotherapy. And you can actually change their microbiome and make them respond better to cancer or therapy. And so we saw this as an opportunity to study this in patients.

And so what we did is we collected both oral and gut microbiomes samples from hundreds of patients with metastatic melanoma. And what we found when we looked specifically at patients being treated on immunotherapy is that patients who had a higher diversity of bacteria within their gut microbiome did much better on therapy. And specifically, this is a form of therapy called anti-PD1, whereas patients who failed to respond to therapy had a much lower diversity of bacteria.

IRA FLATOW: Now, does that–

JENNIFER WARGO: Now–

IRA FLATOW: I’m sorry. Go ahead.

JENNIFER WARGO: No, on top of that, we also saw the diversity of the microbiome matters. But also, we looked at not only how diverse is the microbiome, but what bacteria are actually there. And so we also saw differences in the composition of the microbiome, the gut microbiome between responders and non-responders.

IRA FLATOW: Were you able to– going back, referring back to your mouse study, I remember that study. They gave specific probiotics to the mice, right?

JENNIFER WARGO: Correct. Correct. And that was landmark work done by both Tom Gajewski from the University of Chicago, and by Dr. [INAUDIBLE] from the University in France, [INAUDIBLE]. And I was not on those studies, but I actually saw those studies presented at the annual meeting of the Society for the immunotherapy of cancer. And I was completely floored when I saw the data presented. And I got up to the microphone, and asked Tom’s post-doc, essentially, this is amazing data. Have you studied this in patients? And at the time, they hadn’t. And so, again, we saw this as an opportunity to see if what was going on in the mice was going on in patients.

IRA FLATOW: But could you define the exact probiotics in the mice, the exact bacteria in the mice that were affective?

JENNIFER WARGO: Right. And so in Tom Gajewski’s study, bifiobacteria was actually determined to be the driver of enhanced responses to therapy. And so we wanted to see if the same type of bacteria was driving the response in patients.

IRA FLATOW: And did you find the same thing?

JENNIFER WARGO: Well, we found something a little bit different. And that’s probably understandable given the difference in the microbiome between the mouse and man. What we found was that we didn’t necessarily see bifidobacteria as a major driver. We saw other bacteria, including bacteria in the clusterdialas rumenacaucus bucali bacteria group as being more abundant in the gut of patients who responded to the immunotherapy.

IRA FLATOW: OK, can you actually buy that bacteria and eat it yourself if you want to?

JENNIFER WARGO: No. No. That’s a great question. And I think but what you’re driving at is could you actually change the microbiome to enhance responses to therapy not only in mice, but how about in patients? And that’s exactly what we hope to do. Now, how do you change the microbiome? You can do it in a couple of ways. One way is certainly something called fecal microbiome transplant, or give someone a poop pill, where you essentially take a microbiome from another person and put it into that person with cancer, treat them with immunotherapy, and hopefully make them respond much better. And so we’re going to be working. We’re working with the Parker Institute for cancer immunotherapy and industry partner to do just that, to implement a clinical trial to see if we can do that.

IRA FLATOW: And what are the pathways that the gut bacteria are able to influence the cancer in how these therapies work?

JENNIFER WARGO: Yeah, and I think that’s a great question. And as you highlight, in our bodies we have trillions of microbes. The largest proportion of these are in the gut. And all along– the gut has a very large surface area. And all along that surface area, the gut bacteria can actually interact with immune cells via metabolites, or either [INAUDIBLE] receptors, and cytokines, or can do cytokine responses, or rather more distant effects from those local phenomenon within the gut, which then we believe is influencing not only the sight of the tumor, but overall immunity.

IRA FLATOW: Mm-hm. So how does how does it work on the tumor?

JENNIFER WARGO: Well, what it does is– what we think is happening is that when more favorable gut microbiome, in our paper when we actually looked and profiled the gut microbiome and compared it to the immune cells within the tumor, we found that patients who had a more favorable gut microbiome with more rumenacaucus clustradialis bucali bacteria actually had a higher density of t-cells, or killer t-cells in their tumor. And these t-cells were more activated. They expressed more markers of cytolytic markers.

IRA FLATOW: So wait. Do think there was a genetic background to this, why one population of people has more, the gut bacteria than another?

JENNIFER WARGO: Well, it’s probably a number of different factors. I think one factor is certainly diet. I think diet plays a major role as far as what you eat critically influences your microbiome. I think medications can actually affect the microbiome. One big class of medications that can affect the microbiome is antibiotics. You know Lawrence [INAUDIBLE] Vogel, who also published in science this week, looked at a group of patients, cancer patients, who were treated with, again, immunotherapy, and found that if they had received antibiotics just before, just after they started treatment, that the therapy was much less effective.

IRA FLATOW: You had a study out last month that looked at how the bacteria on the tumor might affect chemotherapy. What did you find there?

JENNIFER WARGO: Correct. Yes. That was work that I did with a group from Harvard. And what we found is we’ve been studying how to potentially try and enhance responses to cancer therapy for a number of years. And we had done studies in tumors of patients with cancer. And what we found and it was that in about 75% of patients with pancreatic cancer, we can actually find bacteria which were capable of breaking down chemotherapy, namely gemcitabine.

IRA FLATOW: Is that a good thing or a bad thing?

JENNIFER WARGO: Well, it’s bad for the person, certainly.

IRA FLATOW: You don’t want it to break down the chemo.

JENNIFER WARGO: It breaks down the chemotherapy and makes it ineffective. And I think it’s tricky because you say, well, gosh could you just treat someone with chemotherapy and an antibiotic. But now we know that the antibiotics can actually affect the gut microbiome. So there’s a delicate balance here.

IRA FLATOW: Yeah, so where do you go from here with your studies? You try to isolate what are the good bacteria and do further studies in people?

JENNIFER WARGO: Absolutely. And I think the critical point here is that we certainly have some knowledge of this, but there’s still a great deal to learn. There’s amazing people worldwide looking at this, and we’re all working together as a group to better understand this. And that’s the ideal way to do it. A couple of ways to do it, certainly by running the clinical trials, to actually test whether or not if we change the microbiome that we can actually make people respond better to cancer therapy.

And again, we’re working with the Parker Institute and others worldwide to do that. But also, critically, taking samples from these patients, and papers like this, and saying, OK, what’s common between these patients, and based on this signature, could we actually identify, not just use fecal transplant, but could we identify a consortia of bacteria that we could give to a patient, which we could then hopefully would help mediate better immune responses and better responses to immunotherapy.

IRA FLATOW: Because you never know how the bacteria depend on each other. You take them out of their home, right?

JENNIFER WARGO: Absolutely. Absolutely.

IRA FLATOW: And so when scientists now are talking about cancer therapies, they’re actively discussing including immunotherapy and putting some bacteria in, or some sort of probiotics, or a poop pill, or something like that. And they’re not thinking as it’s isolated immunotherapy.

JENNIFER WARGO: Correct. And I think what we’re starting to understand is that the microbiome can influence responses even to chemotherapy. And Dr. [INAUDIBLE] showed that previously. And so I think this has widespread implications. But it’s early days. And I think anyone who’s thinking about patients should certainly work with their providers, shouldn’t really try this on their own. I think it needs to be done in the context of carefully planned out clinical trials. But I think ultimately, we’re going to get there.

IRA FLATOW: And what is your exact next step? What are you doing next? More trials?

JENNIFER WARGO: Definitely. So I think this was what we call a retrospective analysis. So this was looking in patients who were on treatment, just looking at the signatures. Now we’re doing a prospective trial where we actually enroll patients with cancer that are getting treated with immunotherapy and then we’ll be treating them either with a fecal transplant or with other ways to manipulate the microbiome. And then we’ll do a very careful assessment. How effective are we at actually manipulating the microbiome? And have we improved responses?

IRA FLATOW: Do you always look for patients? Do you need patients for studies like this?

JENNIFER WARGO: Absolutely. The studies aren’t open quite yet, but we’re hoping they’ll be up in the next couple of months. But definitely. And the patients really contribute to this. We owe it to the patients because they’re the ones who donated the samples to really help us better understand this.

IRA FLATOW: Yeah, because we always talk about studies. But we read ourselves as journals how few patients you can get sometimes looking for studies when you actually need them.

JENNIFER WARGO: Yeah.

IRA FLATOW: Yeah. Well, we wish you very good luck on this Dr. Wargo.

JENNIFER WARGO: Thank you so much.

IRA FLATOW: Jennifer Wargo is an author in that study that was published in science. She’s also a professor of surgical oncology and genomic medicine at the University of Texas M.D. Anderson Cancer Center. Of course, that is in Houston. We’re going to take a break. And afterwards, we’re going to expand out and get a grand tour of the microbiome, a look at a microbial map of the world. You want to talk about your own? We’re going to swamp the whole earth here in search of the variety of microbiome. As they used to say in Wide World of Sports, we’ll be back after this break. Stay with us.

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