The microbiome is the complex and diverse collection of microorganisms that live in, and on, our bodies. Recent research has revealed a strong connection between the microbiome and cancer, with many scientists believing that it plays an important role in both preventing and promoting cancer.
As more studies are conducted into this intriguing relationship, understanding how our microbiome can affect different types of cancer could help us to develop treatments for this potentially deadly disease.
In this article, we explore what current evidence tells us about the link between cancer and the microbiome, including how it works and what it means for those affected by cancer.
What do we know about the relationship between gut microbiome and cancer?
We currently know that gut microbes have been linked to both promoting and inhibiting cancer—and can also affect cancer treatment success rate.
Research into the relationship between the human gut microbiome and cancer has revealed a complex web of connections. The microbiome is known to be able to influence multiple aspects of cancer development, including initiation, progression and metastasis.
Microbes can potentially cause metabolite dysbiosis, immunosuppression and promote cancer via:
- Mucosal dysregulation
- Aberrant signal transduction
- Genetic/epigenetic regulation.
Microbes can potentially inhibit cancer through:
- Immunostimulation
- Immunity boosting.
With these facts in mind, it’s clear that the microbiome can possibly be a powerful factor in cancer development, both for and against. Understanding how our gut microbiome contributes to cancer can help us devise treatments or preventive measures that take advantage of this relationship.
Does cancer change the microbiome?
The tumor microenvironment (TME) has unique conditions, such as immune inhibition, and angiogenesis, making TME a rich environment. TME has low oxygen concentration, making it anaerobic. As such, TME favors anaerobic bacteria such as:
- Bacteroides fragilis
- Enterococcus faecalis.
It’s also important to note that different cancers have different TME implications. While colorectal cancer TME links to B. fragilis and Enterococcus faecalis, breast cancer, on the other hand, links to Enterococcus and Streptococcus.
These differences in TME microbes by cancer type illustrate that microbiome shift induced by cancer is multivariate, which means that cancer-induced microbiome changes are not predictable and are subject to the specific type of cancer.
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How the microbiome affects different types of cancer
Due to these differing TMEs, how the microbiome affects different types of cancer also varies.
For instance, research suggests that certain gut microbiota can promote colorectal cancer progression. On the other hand, in breast and ovarian cancers, it is thought that specific strains of bacteria can inhibit tumor growth and metastasis.
Therefore, understanding the connections between the microbiome and each type of cancer is key when considering treatment options, which is what we’ll do in the sections below.
How does the gut microbiome affect colon cancer?
Gut microbiome has been connected to tumorigenesis in colon cancer by:
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Inducing DNA damage and epigenetics alterations
IBD can induce DNA damage and, in turn, lead to colon cancer.
Morganella morganii increases intestinal permeability in mice and fuels colon tumorigenesis in mice. pks and E. coli also induce DNA damage on colonic epithelial cells through bacterial toxin, colibactin, which correlates with faster colorectal cancer (CRC) onset.
Other microbiota (Klebsiella pneumoniae, Enterobacter aerogenes, Citrobacter koseri) also express colibactin. Genotoxin then produces gut microbes that can double-strand DNA damage:
- Helicobacter pylori
- Bacteroides fragilis
- Salmonella enterica
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Interfering with host DNA damage response
For example, p53 protein hardwires malignant cells to commit apoptosis, cellular self-destruction, but, for example, H. pylori can degrade p53 to lead the resistance of cells to apoptosis. Apoptosis-resistance is a cancer predisposition.
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Triggering aberrant signaling cascades
For example, Wnt signaling is determinant for cell fate, and its modulation may trigger tumorigenesis. Fusobacterium nucleatum modulates the Wnt pathway and promotes CRC tumors.
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Inducing immunosuppression
For example, F nucleatum can recruit tumor-infiltrating myeloid-derived suppressor cells to suppress immune responses. H pylori induces programmed cell death on gastrointestinal epithelial cells whereas H pylori infected cells can escape immune surveillance, promoting carcinogenesis.
How to define risk of colorectal cancer based on fecal microbiome
There are both cancer promoting and inhibiting microbes in the gut. Inhibiting microbes from healthy people can be delivered in the form of fecal microbiota transplantation to inhibit cancer.
Cancer promoting microbes often reside adjacent to gut epithelial cells, and mucosa. Hence they can be observed in the fecal microbiome. Nonetheless, feces and digestive tract mucosa are two different tissues and have different microbe composition.
Hence, fecal microbiome may not be enough alone for defining CRC risk. Therefore, other sample types such as colon mucosa biopsies may be required.
How does the gut microbiome affect lung cancer?
Immunotherapy is often employed against non-small cell lung cancer (NSCLC). L rhamnosus triggers dendritic cells and stimulates antitumor activity of immunotherapy in lung cancer patients.
Bifidobacterium maturates dendritic cells and promotes immunotherapy success against NSCLC. Fecal microbiome transplants are also evaluated as therapy for NSCLC.
How does the gut microbiome affect breast cancer (BC)?
Bacteroides fragilis, a common gut resident, may express Bacteroides fragili toxin (BFT). BFT application on breast cancer cell lines exacerbated tumor growth.
Enterococcus and Streptococcus, two other common gut resident taxa, are also found in BC TME, and are involved in reorganization of cellular cytoskeleton and metastasis. According to one report by Cell Host & Microbe:
“Building off of findings by Bullman et al. in colorectal cancer that tumors and their paired metastases share a common microbiome, and that this microbiome is viable and may promote survival of cancer cells (Bullman et al., 2017), the present study by Fu, Yao, and Dong et al. pushes us once again to reimagine the potential role of the microbiome in cancer metastasis (Fu et al., 2022).”
Depletion of gut microbes in mice with antibiotics increased BC progression rates. There are clinical trials to intervene gut microbiome with probiotics against breast cancer.
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How a rich microbiome can protect against cancer
Some microbes promote cancer, some microbes suppress cancer. Richness of harmful bacteria may promote cancer, whereas richness of beneficial microbes may inhibit cancer.
Having a species rich and diverse microbiome increases the chance of harboring anticancer microbes that would act against tumor and tumor-promoting microbes.
One of the adverse events of radiotherapy is gut microbiota dysbiosis, which is typically characterized by a relative decrease in the richness of favorable microbes, e.g Bifidobacterium, and an increase in the relative richness of harmful microorganisms such as Fusobacteria and Proteobacteria.
These changes in the composition of gut microbiota in turn exacerbates radiation-related complications, such as radiation enteropathy.
Gut microbiome impact on cancer treatment
Administration of Enterococcus and Barnesiella can increase the antitumor efficacy of chemotherapy, L rhamnosus triggers dendritic cells and stimulates antitumor activity of immunotherapy, and Bifidobacterium maturates dendritic cells and promotes immunotherapy success against NSCLC.
Radiotherapy to eliminate cancer cells often decreases gut microbiome diversity, and lays a framework for toxicity. Enriching and diversifying gut microbes may protect against toxic impact of radiotherapy.
Gut microbiome projects treatment prognosis post-surgery to remove colonic tumors, for example:
- Low microbial diversity and mucin-degrading members of the Bacteroidaceae and Lachnospiraceae families are associated with postoperative anastomotic leaks.
- Anastomotic leaks can cause infections, and some microbes can avoid infections. For example, some strains in Lactobacillus and Bifidobacterium are capable of inhibiting the growth of clinically isolated methicillin-resistant Staphylococcus aureus which infects as a postoperative pathogen.
Closing thoughts
The gut microbiome has the potential to make a profound impact on cancer therapy, from influencing the efficacy of cancer therapies to being able to protect against toxic effects. This is why it’s essential for researchers and clinicians alike to consider how these microbes interact with our bodies when treating patients with cancer.
By understanding the role that microbial communities play in colon carcinogenesis, pancreatic cancer, and other forms of malignancy, we may be able to develop better treatments tailored specifically for each patient’s unique set of microorganisms.
With continued research into this field and an increased focus on anti-cancer immune checkpoint blockade strategies involving microbial elements, there is hope that someday soon more effective treatments will become available.
Looking to study the microbiome?
At CosmosID, we offer a state-of-the-art microbiome analysis platform and sequencing services across a vast range of applications.
Whether you’re looking to study cancer and the microbiome, or to study the microbiome in other therapeutic and medical applications, our platform has been built to provide you with accurate, reliable data.
We also offer a comprehensive range of resources and support services for those interested in learning more about how the microbiome can be applied within their research or clinical practice.
Get in touch today to learn more!
Cancer and the Microbiome: A Handy Infographic
Cancer and the microbiome: FAQs
Can the gut microbiome cause cancer?
While there has been no definitive causal link of gut microbiome to cancer, research continues to show possible links to the pathogenesis of some cancers, with different microbes found in the gut associated with different cancer promoting or inhibiting mechanisms.
Does the microbiome help the body fight cancer?
Gut microbiomes have not been definitively associated to be connected to cancer treatment, however continuing research shows that microbiomes may fend off cancer and improve cancer treatment efficacy, with different microbes having different cancer suppressing and therapy improving mechanisms.
How does cancer affect the microbiome?
The cancer tumor microenvironment harbors anoxic, vascular environments with lack of immunosurveillance creating vastly different environments than healthy tissues. Different microbes than those in healthy tissue can survive in TME.
How does the gut microbiome affect inflammatory bowel disease?
Bacterial toxins secreted in the IBD gut may induce DNA damage and promote tumor progression. Klebsiella pneumoniae, Enterobacter aerogenes and Citrobacter koseri isolates H. pylori, Bacteroides fragilis, Salmonella enterica, E. coli isolates are known to secrete toxins that have the potential to progress IBD to colon cancer.
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