The recent realization that the microbiome impacts human health and disease states, as well as the rapid evolution of research tools has led to an exciting and critical juncture, when we can now go deeper than ever in understanding and using microbiome science for cancer detection.

Shifting paradigms is often an uphill battle, especially in science. It’s easy to get stuck in a particular dogma, and difficult to break away from it. But progress demands it, particularly when applying new knowledge to spur medical advances.

There have been countless examples of this over the years. Think of the theory of spontaneous generation, which hampered advancement in tackling the transmission of infectious diseases. It took hundreds of years to disprove the theory and get buy-in from the medical and patient communities.

When it comes to the role of the microbiome and disease, people have long been wed to the idea that disease is usually caused by one bad element, such as a strain of e-coli, or salmonella. Opening minds to the idea that, when it comes to microbes, the community they form has a huge impact on disease and even health has been a tougher sell.

It’s now time to break the paradigm about the role of the microbiome and human cancer. As the respected researcher and director of Pacific Biosciences Research Center, Margaret McFall-Ngai, put it: “It took a while to move from the geocentric to the heliocentric view of our universe. So, we have to expect that it will take time to move from a human-centric to microbial view of the world.”

While scientists have waded into theories surrounding the relationship between cancer and microbes for hundreds of years, it was only recently that research has put the pieces together to demonstrate the undeniable link of the microbiome.

To better understand the cancer/microbiome relationship, it’s important to start with some perspective. Historically, the medical world has recognized that most human disease–at least when not caused by infection–comes from the human genome. While true, more advanced research shows that human disease also stems from microbes—trillions of types of bacteria, viruses and fungi, which we interact with on a daily basis.

The microbiome has been around far longer than humans—microbes existed for 3 billion years before humans. In fact, we have evolved in a microbial world—they interact and make up about 99 percent of the genes found in or on our bodies. They don’t just give us diseases, they help us, too. For example, when people are badly burned, they have a difficult time healing because they’ve lost the beneficial microbes that exist on skin that would normally help them heal. In the gut, the microbiome helps process nutrients in food so that they can be absorbed by the body.

We have this vision that microbes are bad and can lead to diseases. But the vast majority are essential to our well-being. Microbes also rarely operate in isolation. They typically form a very diverse community, based on their location in the body or the environment.

One thing is now becoming clear: the microbiome plays a key role in the biology of cancer and Micronoma has been able to show that different microbiome communities can be found in different tissues; that this diversity extends to tumoral vs. healthy tissue.  And one major applicable finding is that signatures of these diverse communities can be found in blood. With Micronoma’s groundbreaking development of a liquid biopsy to detect these microbial elements in tumors, there is hope on the horizon for earlier detection, even for the deadliest of cancers, such as lung and pancreatic cancer.

 

What technological progress made this possible? Next Gen Sequencing (NGS) and big data AI/bioinformatics 

While buy-in to the link between the microbiome and cancer is one piece of advancing this science, until recently, the technology to support it hadn’t been available. Consider the fact that there is one human genome to analyze (about 23,000 genes in total), while there are thousands of microbial genomes (collectively representing about 2,000,000 genes!). The cost of NGS had to be significantly lowered to enable the sequencing at scale of many samples in order to have enough power for statistically valid analysis.

In addition, the computing power and data storage, and the costs of them, required to analyze all the data associated with the microbiome analysis were overwhelming and prohibitive. But today there are solutions that are more affordable and, as is typical with maturing technologies, we are seeing an improvement in performance as the cost keeps decreasing.

Back in 2017-2018, Micronoma’s chief analytics officer, Greg Poore, and co-founder, Rob Knight, dedicated countless hours to creating an analysis pipeline to identify and sequence signatures of microbial DNA and RNA in tumors and in the blood. Drawing from the Cancer Genome Atlas to analyze data from more than 17,000 samples, the team was able to use the signatures to distinguish between certain cancer types and cancer stages within those types, as they were able to publish in Nature in 2020.

Technology has now advanced to a place where the Micronoma team is creating a massive database and analysis platform to enable the use of the microbiome in circulating blood as an early cancer detection tool that can be reasonably priced for use by healthcare systems. 

There is an endless amount of discovery ahead with regard to the relationship between the microbiome and cancer. The Micronoma team has launched the science and tools necessary to accelerate this line of research. Eventually, this investment of resources will result in a better understanding of cancer biology for improved detection and even potential new treatments of cancer, saving countless lives.

At the end of the day, taking the blinders off and accepting paradigm shifts in science can be intimidating, even a bit frightening. But if science is to advance to a point where it can identify more cancers early enough to effectively treat them, the community must summon the courage to do just that.