Periodically, the Office of Philanthropy invites City of Hope® leaders, faculty and researchers to have a conversation about their groundbreaking work.
Robert R. Jenq, M.D., is the director of the City of Hope Microbiome Program and a clinical professor in the Department of Hematology and Hematopoietic Cell Transplantation. He specializes in treating patients diagnosed with leukemia, lymphoma and other types of blood and bone marrow cancer. We talked to him about the growing interest in the microbiome and its effects on human health, including cancer outcomes.
Dr. Jenq, tell us about the microbiome. What is it, and why are we hearing so much about it lately?
The microbiome is the study of microbes and how they affect us as human beings. Those microbes include bacteria, viruses and fungi. They live inside us and on our surfaces and, for the most part, they're naturally occurring. The microbiome is really dynamic and varies between individuals.
This field dates back centuries. However, it really became more mainstream in the 2010s after completion of the Human Genome project and the development of sequencing technologies.
It’s clear that scientists, and now the public, are starting to better understand the microbiome’s influence on human health. How does it relate to cancer?
Cancer and its treatments, like chemotherapy and radiation, suppress the immune system. So, patients with cancer are all, to varying degrees, at risk of infections.
But we’ve come to realize over the last 10 years that the microbiome gets injured when you give patients antibiotics, and these patients are at higher risk for certain complications. In bone marrow transplant patients, we see more neutropenic fever, which can be a medical emergency. We see graph-versus-host-disease, which can be life-ending.
Additionally, cancer immunologists started noticing that patients getting checkpoint inhibitors didn't respond as well to the therapy if they had received antibiotics. Same thing with CAR T cell therapy patients.
It turns out that these cancer therapies rely on a normal microbiome to work effectively. So, we’re trying to figure out why — and can we do something about it?
“It turns out that these cancer therapies rely on a normal microbiome to work effectively. So, we’re trying to figure out why — and can we do something about it?”
— Robert Jenq, M.D., director of the
City of Hope Microbiome Program
Tell us an example of something you uncovered from your research.
I study bone marrow transplantation. Bone marrow transplant patients have some of the most injured microbiome profiles.
Over time, we noticed that certain antibiotics were associated with more injury to the microbiome than others. For example, meropenem and cefepime are two antibiotics that can be used to treat fever in bone marrow transplant patients. They're considered equivalent, but meropenem is broader and kills more bacteria. Cefepime is more targeted.
We went back and looked at the data. It turns out, when doctors used meropenem or a similar antibiotic instead of the more targeted cefepime, patients went on to have more graft-versus-host-disease, which is a life-threatening complication of a transplant.
We replicated that finding in the lab using mice. Stronger antibiotics caused more graph-versus-host-disease in the mice as well. And we were able to pin the issue on changes to a certain type of bacteria.
City of Hope is one of very few cancer institutions in the world that has recognized the importance of microbiome health in fighting cancer. As the new leader of City of Hope’s Microbiome Program, what are your goals for the future?
There are a lot of people doing great microbiome work at City of Hope already. First and foremost, we need to support these folks, and we are.
Second, we're introducing new tools and building a formal infrastructure to facilitate sample collection for microbiome studies. We're working with folks in our Integrative Genomics Center to develop new microbiome sequencing assays and metabolomic assays that will give us more richness to the data we collect. We’ve hired computational scientists and biostatisticians to help analyze that data.
Third, we want to recruit the best microbiome scientists from across the globe. We’ve already successfully recruited Kenya Honda from Japan. He’s amazing. I’ve been reading his microbiome studies in top journals since 2010. In addition to Kenya, we want to hire another two to three faculty over the next couple years. We're also looking to hire basic bacteriologists, immunologists and AI experts.
As City of Hope’s program evolves, do you foresee a future where we might develop personalized microbiome-based therapy for specific diseases like cancer?
It’s still early days, but there’s a lot of potential. In terms of personalized microbiome treatments, a mentor of mine, Eric Pamer at University of Chicago, likes to think about microbiome science like blood banking.
With high-risk surgery, surgeons will often have the patient bank some of their own blood so it's available if they need it. What if we could do the same thing in our cancer patients? Could we store their microbiome and give it back to them after they're done with the antibiotics?
Doctors have also been recommending prebiotics to patients. Previous studies on this have been disappointing, but that’s because it hasn’t been fully personalized. We all have different types of bacteria in us. We all tend to eat different types of food. So, what works for one patient may not work for others. In the future, prebiotics could be tailored to that patient based on knowledge of their diet and microbiome.
You’ve had a long career at many prestigious cancer centers. What inspired you to come to City of Hope to lead the microbiome program?
City of Hope is really a special place. There's this fearlessness about the folks doing research here. Researchers take on challenges that are usually in the realm of biotech or the pharma industry. It’s really unique, and philanthropy is perhaps the biggest reason why that’s possible.
“City of Hope is really a special place. There's this fearlessness about the folks doing research here (…) It’s really unique, and philanthropy is perhaps the biggest reason why that’s possible.”
— Robert Jenq, M.D., director of the
City of Hope Microbiome Program
Finally, we know that everyone can benefit from a healthy microbiome, right? Is there something people can do to support or improve their own?
If you want to boost your microbiome, you can. You can eat a variety of different fruits and vegetables, every type of grain.
All these foods contain different types of complex sugars, and each type of complex sugar will feed a different type of bacteria in your intestinal tract.
You know how a pregnant woman might say, “Oh, I'm eating for two.” Well, because we all harbor thousands of microbes, we're actually eating for thousands.
So, eating a diverse and balanced diet can help beef up your microbiome.