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How Gut Microbiota May Influence Cancer Therapy

Hundreds of trillions of microbes that inhabit our colon – gut microbiota – might influence the development of Alzheimer’s and Parkinson’s disease, epilepsy, autoimmune diseases and even cancer. They may also help in determining whether treatments or therapies work. Cancer is a multifactorial pathology and is the second leading cause of death worldwide. It has long been recognized that our immune system is a dominant force in controlling carcinoma, or cancer.

How Gut Microbiota Impacts Immunotherapy in Cancers

Defects in immunity contribute to not only cancer progression, but also to poor responses to cancer therapy. Multiple studies support the notion that the gut microbiome impacts the potency of immunotherapy and some chemotherapies. Pioneering work of investigation proved that intestinal microbiota was essential for optimal responses to certain types (CpG-oligonucleotide) of immunotherapy. 

Also, the gut microbiota shape the anti-cancer immune response by stimulating generation of a specific subset of “pathogenic” Th17 (pTh17) cells and memory Th1 immune response after treatment with immune-stimulatory chemotherapy cyclophosphamide. DNA sequencing of stool samples identified an association between gut microbiome composition and subsequent therapeutic response. 

Emerging Role of Microbiome in Cancer Immunotherapy

A study published in the reputed journal Science investigated the gut bacteria of 249 people who received immunotherapy for different types of cancer, some of whom had also taken antibiotics. It was found gut bacteria differed between people who responded well to immunotherapy and those who didn’t. People who positively responded tended to have more of a particular bacteria called Akkermansia muciniphilia. This early-stage study gives us some insights into factors that might influence people’s responses to cancer treatment (immunotherapy with monoclonal antibodies).  

Abiraterone acetate, a highly effective therapy to treat prostate cancer, is taken orally.  It reduces androgen in the human body. Dr. Jeremy Burton, Lawson scientist, associate professor at Schulich Medicine and Dentistry wondered if the gut microbiome had a role in this.

When drugs are taken orally they make their way through the intestinal tract, where they come into contact with billions of microorganisms.”

Genomic analysis identifies association of Fusobacterium with colorectal cancer.  Professor Emma Allen-Vercoe, University of Guelph, points out in a study, “Fusobacterium is found in and around one third of bowel cancers,” Two patients in this study had lots of Fusobacterium intheir microbiome, which dropped after treatment. “This has given us hope that applying a microbiome drug could remove some of the ‘bad’ bacteria in people with bowel cancer,” the professor says.

Fusobacterium nucleatum has been implicated in various types of cancer, including colorectal cancer, oesophageal cancer, gastric cancer, head and neck squamous cell carcinoma, and pancreatic cancer.

Cancer researchers now realize that many of those seemingly harmless microbes produce DNA-damaging toxins and carcinogenic metabolites, induce cancer-promoting inflammation, make tumours more resistant to chemotherapy drugs, and suppress the body’s anticancer immune responses.

“Every day now there seems to be some new microbe associated with cancer,”

says Susan Bullman, a microbiologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington

Microbiologist Jun Yu of the Chinese University of Hong Kong believes bacteria plays a major role that bacteria plays in promoting stomach cancer. Yu’s team identified a handful of microbes that were consistently enriched in samples from people with gastric cancer or precancerous stomach lesions. “H. pylori is not the only bad guy,” she says.

The human gut microbiota regulates many host processes like metabolism, inflammation, immune and intestinal epithelial cell responses. Significant progress in cancer development has been noted in interaction with microbiomes. Intestinal dysbiosis or the deviated repertoire of gut microbiota has been associated with chronic inflammatory disorders.

The composition of the intestinal microbiota influences the effectiveness of anticancer drugs (such as immunogenic chemotherapies and immune checkpoint blockers) and regulates tumor immunosurveillance, 

Modulation of Microbiome to Fight Cancer

So, all eyes are now on the discovery of beneficial microbes that will enhance the efficacy of immune-modulating drugs known as checkpoint inhibitors and mitigate toxicity. “Modulating the microbiome makes complete sense,” says Jennifer Wargo, a surgical oncologist at the University of Texas MD Anderson Cancer Center in Houston. 

Modulating the microbiota with proper use of antibiotics, probiotics, faecal microbiota transplant or nanotechnologies may potentiate the antitumor effects of chemo drugs or immune checkpoint inhibitors. Again, GI surgery, including preoperative cleansing with oral and intravenous antibiotics, might alter the microbiota diversity that may lead to complications such as infection and anastomotic leakage.

These complications may be ameliorated by modulating the microbiota as bacteria like Lactobacillus spp and A. muciniphila regulate intestinal wound healing process. Tumor-associated bacteria may be identified as diagnostic or prognostic markers for cancer. Microbial signature may be used to distinguish patients with cancer for more effective treatment, therapies or to reduce treatment complication.

Understanding how the mechanisms of microbiome influence cancers – directly and indirectly, harmfully and beneficially – can aid in cancer prevention, treatment and management.  But much of these remain unknown and unexplored. The relationship between microbiome and cancer is complex and multifactorial.

The interactions between microbes, diet, host factors, drugs, and cell to cell interactions involve intricate feedback.  Changes in the microbiome may contribute to carcinoma progression. It is therefore important to genetically sequence the microbiota of oncological patients to evaluate and correct dysbiosis and enable anticancer interventions.