The human body is a complex ecosystem, and within it resides a vast array of microorganisms, particularly bacteria. While most of these bacteria play vital roles in maintaining our health, recent studies have uncovered a surprising twist: some bacteria infiltrate tumours, assisting them in growing, spreading, and evading the immune system’s defenses.
The human body is home to approximately 100 trillion microbial cells. These microbes, predominantly bacteria, inhabit various regions of our body, including the gut, skin, respiratory and urogenital tracts, and mammary glands. Surprisingly though, recent scientific investigations have shown that some forms of bacteria also take up residence within cancerous tumours, and help them to proliferate.
A groundbreaking study recently published in the journal Nature has shed light on this phenomenon. The research reveals that bacteria found in oral and colorectal tumours can directly promote cancer progression by suppressing the human immune response and facilitating the rapid spread of cancer cells. Simultaneously, a study published in the journal Cell Reports suggests that certain anti-cancer drugs, such as 5-fluorouracil, may be effective because they target the bacteria that aid tumour development.
Susan Bullman, a microbiologist at the Fred Hutchinson Cancer Centre in Seattle, who led both studies, stated, “Our data suggests that bacteria are not innocent bystanders but instead are shaping the ecosystem in the regions of the tumour where they were located. Bacteria are a viable part of this tumor microenvironment.”
Added to this, Jennifer Wargo, a surgical oncologist at the University of Texas MD Anderson Cancer Centre in Houston, found that melanoma patients with a more diverse population of “beneficial” bacteria in their guts exhibited improved responses to immunotherapy.
Wargo further added, “We even find microbes within brain tumours. You’re like, gosh, how did they get there?”
The recent study focusing on oral and colorectal tumours provides strong evidence that microbes do not merely inhabit tumours but can be found within cancer cells themselves and even within immune cells, highlighting the intricate relationship between bacteria and cancer progression.
These two groundbreaking studies collectively suggest that understanding the interplay between tumours and their resident microbes could hold the key to combating and eradicating specific forms of cancer.
Bacteria’s Role in Promoting or Inhibiting Cancer Growth
The notion that bacteria can influence cancer’s course dates back to the late 19th century when German physicians Wilhelm Busch and Friedrich Fehleisen independently observed that certain tumours would shrink after patients contracted erysipelas, a skin condition caused by Streptococci bacteria. While these observations sparked interest, it was William Coley who developed a treatment known as “Coley’s Toxins,” which comprised heat-killed bacteria, to address osteosarcoma. However, this approach yielded limited success and was ultimately abandoned due to the risk of fatal infections.
Unlike Streptococcus bacteria, which appeared to combat tumours, Helicobacter pylori is classified as a carcinogen and is thought by some scientists to be linked to gastric tumour development.
One specific oral bacterium, Fusobacterium nucleatum, is frequently found in gastrointestinal tract tumours and is associated with poor prognosis and treatment failure. Studies have also suggested that dysbiosis, an imbalance in the gut microbial community, can drive gastrointestinal cancers. Conversely, certain bacteria in a patient’s gut have been linked to improved outcomes with immunotherapy.
Building on these findings, Susan Bullman’s 2017 study published in Science revealed that Fusobacterium nucleatum and other bacteria were not only present in primary colorectal tumours but also in metastatic cancer cells that had spread from the original tumour.
To further investigate the role of bacteria in cancer, Bullman conducted experiments wherein tumours containing Fusobacterium were implanted into mice, followed by antibiotic treatment. This led to the elimination of both bacteria and a reduction in tumour size, providing evidence that Fusobacterium was linked to cancer’s growth and survival.
“Over 10 years ago, advances and accessibility in sequencing technologies had hinted at the possibility of bacterial communities residing within human tumour tissue,” Bullman noted. “But there was very little known about how these microbes got there and what they were doing. We didn’t have the tools or technologies that allowed us to look at this component of the tumour.”
Drugs Targeting Microbes and Tumours
Recognizing the potential of targeting microbes to treat and potentially prevent cancer, Bullman embarked on a study in collaboration with molecular microbiologist Christopher Johnston from the Fred Hutch. They concentrated their efforts on oral and colorectal cancer tumours, as previous research had implicated bacteria in their development.
The research team collected tumour samples from 11 patients and divided each sample into four pieces of tissue. They employed 16S ribosomal DNA (rDNA) analysis to identify and characterize all bacteria present in the tumour samples, with Fusobacterium emerging as the most prevalent bacterium.
However, further investigation using higher-resolution techniques revealed that bacteria were not uniformly distributed throughout the tumours. Instead, most patients exhibited uneven distribution of bacteria within tumour tissue, resulting in bacterial “hotspots.”
Areas of tumours containing bacteria tended to be more immunosuppressed compared to bacteria-free regions. These areas had fewer blood vessels, reduced levels of T cells (immune cells responsible for destroying cancer), and higher levels of myeloid cells (which promote tumour growth by suppressing immunity). Moreover, cancer cells located in bacteria-rich regions displayed enhanced proliferation and migration capabilities.
To confirm the direct role of bacterial infections in cancer progression and immune evasion, researchers infected colorectal cancer cells from patient tumours and cultivated them in the laboratory to form cancer spheroids—a model that mimics tumours.
“In the presence of Fusobacterium, cancer cells increased their migration, so that they can move away from the central tumour,” Bullman explained.
Furthermore, bacterial infection led to the entrapment of neutrophils, white blood cells responsible for defending against infections, at the core of the infected cancer spheroids. This allowed cancer cells to escape T cells. Additionally, in the presence of bacteria, tumour cells migrated individually, carrying bacteria with them—similar to Bullman’s earlier study showing that F. nucleatum often accompanies colorectal cancer metastases.
Johnston highlighted, “Microbes in cancer cells are friends with benefits. There are interactions going on between microbes that are helping cancer cells to survive and progress towards states that are bad for the patient overall.” Not only do bacteria assist cancer cells in evading the immune response, but they also break down or neutralize the chemotherapeutic drugs meant to eliminate cancer cells.
While Bullman’s studies focused on just two types of tumours and a limited number of patients, Jennifer Wargo expressed hope that larger-scale efforts will eventually translate these findings from the laboratory to clinical applications.
