May 1, 2020Laura M. Bolt, PhD
Sandrine Miller-Montgomery, PharmD, PhD, is the executive director for the Center for Microbiome Innovation and professor of the practice in bioengineering at the University of California (UC) San Diego. Her team is focused on expanding industry and academic collaborations of microbiome research in various domains such as clinical application (e.g. new drug pathway identification, novel diagnostic biomarkers identification), environmental science (e.g. identification of natural products from ocean sediment), and the consumer world (e.g. the role of nutrition and diet on our microbiome and metabolome). She also serves as president and CEO of Micronoma Inc.—a start-up out of UC San Diego focusing on early cancer detection using liquid biopsy targeting microbiome biomarkers.
Q: How does an individual’s microbiome relate to their cancer susceptibility and cancer progression?
A: It’s important to keep in mind that human beings do not have just one microbiome, they have many that are very different from each other. For example, the skin microbiome is affected by how much you wash your hands and what kind of lotion you’re using. The gut microbiome is affected by what you eat. When we’re talking about cancer and the microbiome, we are adding an additional level of microbiome study—the microbiome of the cancer, which is very different from the microbiome of the human body. And that’s one of the main points in our recent Nature paper.
Q: What were the main findings of your recent Nature paper?
A: Our first discovery confirmed that cancer tissues are not sterile. Then, we also tested whether the microbiome of the cancer tissue was identical to the adjacent tissue. For lung cancer, we tested whether the microbiome of the lung cancer tissue was different from the microbiome of the healthy adjacent lung tissue. We found that the answer was yes—the cancer had a different microbial signature and the signature was very specific. Then we tried to determine if, by looking at the signature, we could tell if it was lung cancer or breast cancer or prostate cancer. We used a machine learning system and didn’t tell the machine learning system the origin of the tissue we tested. We found that by looking only at the microbial signatures, we could differentiate not only between the cancer and the adjacent healthy tissue, but we could also differentiate which tissue the cancer is coming from. What was really the cherry on the cake was that when we started looking at blood samples, trying to see if we could detect microbial signatures in them, we found that in some cases, the model could predict with very high accuracy—98 percent or higher—what kind of cancer the patient had, whether it was lung or prostate. Our paper is about the various microbiomes that we have in the body’s healthy tissue and in cancer tissue, and the specificity of cancer microbiomes. When it comes to cancer, our findings on the specificity of the microbial signature can enable us to develop a new diagnostic tool.
Q: Why are bacteria present in cancer tissues?
A: We don’t know why the bacteria are there. For example, are they recruited by tumor tissue so that the bacteria can go and digest things invading their environment, like metabolites for example, or are they there because they are a defensive mechanism by the host? We don’t know yet, and like everything in science, it is likely going to be dependent on the type of cancer. Some cancers may recruit, and some may be attacked by the bacteria. We will likely find it to be a combination of host defence and the tumor trying to shelter itself and thrive.
Q: How long have we known about the potential for an individual’s microbiome to impact their cancer therapies?
A: If we go back in history, microbeswere ignored and not understood as being an important component of our interaction with the world, but little by little, their importance has been starting to emerge and is starting to be explored in the microbiome field of science. The fact that the human tissue microbiome has an impact on cancer treatment was discovered in 2017, when it was demonstrated that certain drugs acted differently in responsive and non-responsive patients based on their microbiome profile. The impact of the microbiome on the effectiveness of cancer therapy has been emerging for a couple of years now. However, only the host microbiome was being looked at because, at the time, nobody had looked into the microbiome of the cancer. It was unknown that cancer had a microbiome of its own.
Q: Can you tell me about your company Micronoma?
A: I co-founded a company called Micronoma along with part of the team on the Nature paper. When we started looking at the data used in the paper early in 2018, we realized that it was probably wise to file a patent. So, we filed two IPs at the end of that year, and we started the company in 2019, while we were still generating more data for the paper. Advancing the use of microbial DNA in disease diagnostics is Micronoma’s primary objective as a company. Micronoma is developing the diagnostic assay for cancer detection specifically from blood samples—an assay using microbial markers.
Q: Do you think the microbiome will be given consideration in clinical oncology practice in the future?
A: Now that we better understand thelink between host tissue microbiota and cancer tissue microbiota, treatments that take these elements into consideration are going to be happening more and more. One of the first things is we need is to make sure that the entire oncological community understands that the microbiome of cancer is important, and that we need to avoid contamination of patient samples when they are removed from the body. This is not current practise because no one has known that microbes were important. When it comes to surgery, we hope that we’re going to be able to make a difference in the way that samples are removed so that they are not contaminated and so that they can be analyzed more accurately for microbiota.
Q: What are the key research questions that need to be explored regarding cancer and the microbiome?
A: We need to focus not just on the cancer and the microbiome—we need to look at cancer and the microbiome with the host immune system entering the equation. Once we learn more about the host immune response to the microbiome and/or the cancer, that will likely be when we will be able to make further discovery. Right now, the research is focused on the host response as a stand-alone and trying to develop pathways of genetic offense. But now with our Nature paper, we’re adding a new component, which is the cancer microbiome. The cancer microbiome may be triggering some immune responses or turning down some immune responses that are favorable to the cancer. That’s likely where we’ll find some new research pathways.