Researcher Dr. Ami Bhatt in Conversation

Dr. Bhatt is leading research in a burgeoning field of study: the microbiome and its intersection with cancer treatment.

The study of the microbiome has yielded promising discoveries about the human body and the way genetic material informs our health. Dr. Ami Bhatt, assistant professor of medicine and genetics at Stanford University, and an innovator in the field, is conducting revolutionary research on the microbiome as it relates to oncology. By researching bacteria living in the gut of immunocompromised individuals, Dr. Bhatt hopes to uncover critical information about cancer—for example, how and why the body responds to cancer treatments like chemotherapy. Emerson Collective’s Health Director, Reed Jobs, sat down with Dr. Bhatt to talk about what the research means and what lies ahead.

Dr. Bhatt, start off by telling us a bit about yourself. What's your background and how did you get into this field?

I'm a physician-scientist, trained in internal medicine, hematology, and oncology. Over the course of my clinical training, which was subsequent to getting my PhD in biochemistry, I was really inspired by a set of patients who would often actually be cured of their cancers but would suffer tremendously and sometimes die from the complications of their diseases—or, even worse, the complications of our therapies.

When I did my post-doc, in genomics, microbial genomics, and cancer genomics, at the Broad Institute of MIT and Harvard, I learned how to wield tools that would allow us to interrogate these problems. I joined Stanford about four years ago, where my laboratory focuses on the intersection of those issues, and it's been a really fun and wild ride since being here.

Give us some context around the microbiome. What is the role of the microbiome, both positively, negatively, and its dynamism—how it can change and how it can maybe even be a new therapeutic avenue?

I'll start with how microbes can be healthy and helpful to us. It has been demonstrated that the human intestinal microbiome develops predominately over the course of the first three years of life. And in animal models, the absence of a microbiome results in their immune systems not properly maturing, leading to severe immunologic deficits. We're seeing this now in the broader context, as well: Perhaps you're familiar with the hygiene hypothesis, which suggests that we live too cleanly in the western world. We've become obsessed with antibiotic-containing soaps, and with sterilizing our environment. This has correlated with an epidemiologic rise in diseases like asthma, and allergy.

So there is both direct biological evidence and convincing circumstantial evidence suggesting we need microbes to develop properly, from an immune-system perspective. On the other hand, bacteria, viruses, and fungi can be very dangerous to us as well, in manifestations such as infections.

While we experience a relatively low rate of gastrointestinal infections with bacteria in the United States, we certainly see a lot in the hospital, such as C. difficile colitis, a very severe diarrhea caused by a bacterial organism called Clostridium difficile. But for the most part it does not cause disease unless it finds itself in an environment where all of the rest of the diversity has been knocked out by, for example, exposure to broad-spectrum antibiotics. And in that case, Clostridium difficile acts as a very strong opportunist. It takes advantage of being essentially unopposed, or not kept in check by other bacteria, and it causes disease. So that's an example of a problem that can arise from bacteria.

Researchers are not yet sure how microbes affect the body’s responsiveness to chemotherapy. “It could be that these gut microbes are actually directly modifying the drug,” says Dr. Bhatt. The microbes could also be managing our immune system by sending molecules into circulation that affect how the cancer progresses and how the cancer responds to therapy.

Your work centers around the connection between the microbiome and cancer. Can you talk about that connection? How do we think bacteria are helping or hindering cancer patients?

What we know is that worldwide, about 15 percent of all malignancies or cancers are caused by infectious organisms. You’re probably aware of the human papilloma virus (HPV) and how it can cause cervical cancer. There's also Helicobacter pylori, which has been associated with gastric cancer. There's a long list of these. More recently it has been shown that even with cancers that are not thought to be infectious in origin, or cancers where we haven't successfully identified an infection, the composition of the gut microbiome may actually be important in disease progression.

One of the findings that has been most compelling in our field is a series of studies that have shown that the types of organisms in the microbiome actually impact how well chemotherapy works. I can give the same drug to 10 different patients who all have the same cancer and they will respond differently. One factor that may determine responsiveness to chemotherapy is the composition of the gut microbiome.

Researchers recently found that immunotherapies treat cancers by turning up the immune system. And they work differentially in people who have certain types of microbes versus others, which certainly suggests a compelling link between the microbiome, the immune system, and cancer. So I think what we're finding is that the microbiome may be this tunable factor in getting cancer therapies to work better.

Furthermore, we know and have known for a long time that microbes can impact side effects to cancer medications. Anybody who has known somebody who has had cancer, who has been treated with traditional therapies, knows that it is no walk in the park. Even with modern supportive therapeutics like anti-nausea medications, many of our patients suffer terrible gastrointestinal side effects. Sometimes these side effects are so bad that even if the drug is working for the cancer, we have to stop it because the side effects are intolerable.

It has been demonstrated that the microbes that are in our gut may actually impact whether or not somebody has intolerable side effects to these therapies. We're getting at just the tip of the iceberg of how microbes may impact therapy efficacy, how they impact the natural progression of cancers, and how they may be critical modulators of severe side effects to our drugs.

To what extent do you think the microbiome will be important as a modulator?

This is a big open question. I think our intuition is that the microbiome is kind of like the fine-tuning dial on a radio—and I realize many millennials have never seen a traditional radio, but we used to have radios, and they had two dials. There was a coarse-tuning dial and a fine-tuning dial. The coarse-tuning dial would really change the radio station from 99.5 to, like, 104.5 with a little, two- or three-degree turn, whereas the fine-tuning dial changes things at a much slower rate. So I think about the microbiome being able to fine tune a lot of different aspects of health. The microbiome can probably fine-tune how we respond to cancer therapies. It can fine-tune side effects. It may even fine-tune the interaction between therapies and host genetics.

But right now we're in the very early days of being able to do these studies. In part because technology is ready, but funding also needs to be ready in order to do this. There's certainly more than enough interest. This is an area of burgeoning research. What we need is more engagement in and resources to carry out strong, prospective research studies in actual patients.

“We have a limited amount of data upon which we can draw an intuition, but obviously I have a deep interest in this space,” says Dr. Bhatt. “I'm very committed, as is my lab, to making a difference for patients.”

Why is that? Why do you think this is only emerging as an area of research now?

In part because we have only developed the tools to measure the microbiome effectively and cheaply over the course of the last 10 to 15 years. Another piece of this has been the challenge of the single-minded focus on the cancer itself—not thinking a lot about the context in which the cancer actually exists. I believe that is a mind-shift for at least most Western audiences. If you look at other cultures around the world, there are many cultures where the patient or suffering individual is always seen in a broader context. But for the most part, in Western allopathic tradition, we think a lot about the disease. I think there are physicians, and I'm sure I've fallen into this trap myself, who don't think about Juan, the 57-year-old carpenter who is married and has two kids, who happens to have this disease; it's Juan, the lymphoma patient. So I think part of this is really thinking about people in their context, and microbes are part of our context.

Dr. Bhatt says it was seeing patients who were “basically being cured of their cancer but dying of other things” that really compelled her to think about research in this space. She wanted find a way to extend and improve the quality of cancer patients' lives.

This is all so exciting. This is, like you said, a relatively new field of research, and many people aren't really aware of the microbiome really being talked about in research circles. So, focusing on a lay audience right now, if there were one or two things that you'd really want people to understand about the microbiome today, what would that be?

I think, one, that we live in peaceful coexistence, for the most part, with microbes. And it's even more than that. They're an important part of our health and well-being, such that taking care of our microbes is probably an important part of staying healthy. I think all of us know that intuitively. We know that if we eat the wrong food for an extended period of time, our GI system tells us that. That's a really good reminder that if we take care of our microbes, they will help take care of us, and we need to consider that in a generally healthy diet.

What comes along with that is we've moved beyond an era where we thought of bacteria and microbes as bad. Clearly, they can be good; they can be bad; they can be in the middle. With that in mind, I think we need to be thoughtful about our antibiotic use. Not only should we probably not take antibiotics when we have a viral infection, but I think we need to be thoughtful as a larger community about how we use antibiotics in agriculture and in animal rearing.

Antibiotics are used very broadly, for example, in animals that are reared for consumption by humans because it makes them grow fatter and bigger more quickly. But is that really a good idea? Do we want to be having broad-spectrum antibiotics in our groundwater and broad-spectrum antibiotics, albeit at low concentrations, in the food that we eat every day? So I think that's just another consideration for all of us. Antibiotics when you need them are absolutely critical and antibiotics are one of the great pieces of progress that we've made in medicine and science. But it may be that we're relying upon too much of a good thing. I think those are the key things to keep in mind.