The promise of the human microbiome in cancer research

Trillions of microbes in the human body could play a crucial role in cancer detection and treatment

The promise of the human microbiome in cancer research

Trillions of microorganisms are scattered throughout the human body, outnumbering human cells by a ratio of 10 to one. These living creatures have become an emerging target for cancer treatment.

In a recent U of T-affiliated review, scientists from the Princess Margaret Cancer Centre and the University Health Network have explored research on the complex relationship between the human microbiome and cancer. 

What is the human microbiome?

The human microbiome is the collection of genomes present in the microbes that live on or in humans. These microbes include not only bacteria, but also fungi, viruses, and prokaryotes, wrote Dr. Brian Coburn, a co-author of the study and a professor at U of T’s Department of Laboratory Medicine & Pathobiology.

Most microbes are concentrated in the genital tract and mucosal surfaces, which are the membranes that cover internal organs and various body cavities. A human’s microbiome develops from birth and is influenced by the mother’s microbiota, as well as individual genetic makeup and environmental exposure. 

The microbiome has been suggested to be directly causing cancer through inflammation of mucosal surfaces, systemic impairment of metabolism and the immune system, and influencing the effectiveness of anti-cancer therapy.

Certain bacterial species have been identified as more abundant in patients that respond to certain types of anti-cancer therapies than others, explained Coburn.

Researchers have also found that many tissues have their own distinct bacterial, viral, and fungal populations. Cancerous tissue itself appears to have an altered microbiome. Further evidence shows differences in the microbial composition of specific cancers. For example, scientists have found distinct microbial composition patterns in subtypes of breast cancer.  

How the microbiome could be a target for anti-cancer therapies

Positive responses to anti-cancer therapy are typically “defined by a reduction in the size of their tumor of 30% or more,” wrote co-author Dr. Aaron Hansen, an oncologist at the Princess Margaret Cancer Centre, to The Varsity. “This is a desirable outcome for treatment. Patients who do not respond to therapy typically have a growth of the tumor by 20% or they develop new metastasis.”

Metastasis is the growth of cancer at a secondary site, away from the initial location of cancer. 

Emerging evidence has also described tumour activity as closely related to abnormal microbiota in adjacent tissues. Scientists have suggested that microbiota may cause inflammation ⁠— or altered inflammatory signaling ⁠— in these tissues, which could promote the growth and spread of tumors. However, more research on tissue samples from cancerous and non-cancerous patients is needed to validate the results.

Scientists are looking at ways to manipulate the microbiome in humans, and often use animal subjects to test their hypothesis. These continue to be an important but imperfect tool for testing research hypotheses for human diseases.

“There is some evidence from observational studies and animal models that the gut microbiota is associated with response to some cancer therapies,” wrote Coburn, “but causality [sic] in humans is a difficult thing to definitively prove and this remains an untested hypothesis.”

Probiotics have been considered as a form of additional treatment for approved cancer therapies. In research involving mice, scientists have shown that probiotic supplementation could decrease the number of tumour cells and their proliferation.

Other researchers have found that the introduction of the bacteria Lactobacillus to mice decreased tumour size and improved survival rates, suggesting that altering the microbiome may have an impact on suppressing tumour growth.

The lasting challenge of research in this field

Research in this field has proven challenging because individuals vary in their responses to antibiotics, probiotics, and other interventions that affect the microbiome. There is a wide range of different types of probiotics, noted Coburn, and they can have vastly different effects on different patients, or they can have no effect at all.

“We don’t know what to use, how much, when or for how long and in which patients – it remains a very large research challenge [that] will take decades to thoroughly investigate,” he explained.

Furthermore, animal models “will always be limited in how they are applied to human disease and treatment,” he wrote. “In the end, only human studies (especially randomized controlled trials) can prove or disprove that a new type of therapy is safe or effective.”

Research on the effect of the microbiome on cancer is relatively new. Well-designed, controlled, and structured observational and interventional studies would shed light on this growing field. Such studies would enable clinicians to assess the link between the microbiome and cancer, as well as the microbiome’s potential in cancer diagnosis and treatment.

New research, wrote Coburn, could help clinicians “determine if the relationship is causal or simply coincidence and whether [the microbiome] is a useful therapeutic target.”

Enlightened minds, illuminated research

How the AGO’s art inspires researchers at the Princess Margaret Cancer Centre

Enlightened minds, illuminated research

What does scientific discourse have to do with artistic expression? For a research team at the Princess Margaret Cancer Centre, the answer is “everything.”

We once thought of our right and left brains as separate forces responsible for logical and creative thought, respectively. But scientific progress has shown us otherwise, as mental processes require that the whole brain works together in harmony to approach a task.

Just as the corpus callosum brings our hemispheres together as a band of nerve fibres, so too should science and art harmonize — so believes Dr. Mathieu Lupien, a Senior Scientist at the Princess Margaret Cancer Centre. 

Lupien incorporates art into his professional sphere to generate creative discourse between his close-knit team of researchers. He offers a unique approach to team-building by inviting his team to take a stroll through the Art Gallery of Ontario.

Each team member takes the time to walk through and choose a piece of artwork that speaks to them. Lupien then has the team come together as a group to share their chosen piece and engage in dialogue about what inspired them.

“I get to see the world from their perspective and they get to see mine from theirs,” said Lupien in an interview with The Varsity. The process helps the researchers better understand how they see the world through different lenses.

Lupien expresses that this is an exercise in using something creative, like art, to share who we are as scientists. It gives the team a glimpse into each other’s worlds. For example, if a member really enjoys the intricate detail in a piece, we can understand that the fine details they reflect in their own work are something they value. This helps us interpret the work they do in a more meaningful way.

“Our imagination is the only way to explore the unknown,” said Lupien. “We are working in uncharted territory sometimes, so creating an environment that is conducive to open, creative thought is important for our work.”

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How can students integrate art and science into their own research methods?

Lupien describes that translating scientific works in an intelligible way is an art in itself. Science, technology, engineering, and mathematics can be highly complex areas, full of jargon which can be intimidating for many students interested in the field. Using creative expression is one way to translate complexities in an imaginative way.

He demonstrates this idea in his description of his research on epigenetics: the study of how the activity of our genes can change, without changing our DNA sequences. He describes the genome as six billion letters of DNA that form words that are different in nature. When they are organized into sentences, each of them tells a unique story.

In order to form specific parts of our body, such as muscle and brain tissue, we organize our genome, represented here as letters, in different ways to create distinct sentences. The folding process is guided by epigenetic events, or post-it notes, which highlight the regions of our genome that need to be read.

Perhaps we can say that art relates in the same way. Each stroke of the brush or strike of the pen creates a unique image, and the artist goes over certain areas of the painting with these tools to highlight parts of the piece. Sometimes this disrupts the image, which can create chaos. Other times, this enhances the image with clarity.

Like epigenetics, one must follow these fine lines or broad strokes to understand how the larger image, or genome, has come to be. Lupien emphasizes that fostering creative thought can open a world of possibilities for all walks of life. “Bringing these values into your everyday practice as a researcher can serve to nourish your approach to work,” he said.

Experiencing art can also serve as time for our ideas to incubate, perhaps creating a period of unconscious processing for approaching problems in research. Taking from the famous 1929 works of Graham Wallas, The Art of Thought, incubation allows us to process problems in a manner whereby no direct effort is exerted.

We can optimize the way we process pre-existing knowledge by exposing ourselves to creative mediums such as art. This may lead to new approaches in scientific work. Ultimately, generating a scientific discourse with the expression of art can bring forth creative magic that inspires research. 

“In research, there are two things of value — there is knowledge and creativity,” said Lupien.

“You need to have balance. Never shy away from engaging in creative thought. You never know where it will take you.”