The Association Between the Microbiome and Cancer

Our microbiome consists of living communities of tiny organisms, such as bacteria, fungi, viruses, protozoa, and other microbial organisms that live inside and outside our bodies. Some microbes exert beneficial effects and are often referred to as “good bacteria,” while others can potentially have harmful or pathologic effects and are referred to as “bad bacteria.” 

Dysbiosis occurs when the bad bacteria outnumber the good bacteria and can have many negative effects, such as an increased risk for cancer, weight gain, psychological disorders, GI symptoms, acne, fatigue, and many other unfavorable conditions. 

The microbiome ecosystem can be influenced by genetics, childbirth, geographical location, medications, surgery, environmental exposures, and lifestyle factors such as diet, exercise, sleep, stress, tobacco and alcohol use. Recently, the microbiome's emerging role in cancer research has revealed exciting data supporting the role of the microbiome, especially the gut microbiome, in diagnosing, preventing, and treating some cancers. 

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Unveiling the Microbiome

There are multiple microbiome ecosystems in the human body, each with a unique variation of microbial species. The microorganisms interact in complex and dynamic ways, which can impact the individual systems within the body as well as the overall health and wellness of an individual. The gut microbiome is the most extensively studied and diverse ecosystem within the human body and is the home to trillions of microorganisms. 

There are many functions of the microbiome, including digestion, metabolism, absorption of nutrients, immune system regulation, hormone and neurotransmitter production, vitamin synthesis, and maintaining the structural integrity of the gut mucosa. To support a healthy microbiome and maintain homeostasis, it is important to maintain a healthy lifestyle with regular physical activity, stress reduction, and adequate sleep, and to eat a balanced diet rich in fiber, prebiotics, and probiotics, and low in processed foods and meats. 

It is also recommended to minimize the use of medications such as antibiotics, antidepressants, non-steroidal anti-inflammatory drugs, and proton pump inhibitors unless medically necessary, as these have been found to contribute to dysbiosis.

The Microbiome's Influence on Cancer Development

The relationship between microbiome imbalances and cancer is an active area of research. There is a growing body of evidence suggesting that dysbiosis can increase the risk for some cancers. Several mechanisms are felt to contribute to this. The first is the effect of dysbiosis on systemic inflammation and immune system dysregulation. 

Dysbiosis can cause the intestinal lining to become more porous or “leaky,” allowing toxins, microbes, and food particles to leak out from the intestinal lumen and into the bloodstream, creating a systemic inflammatory response. Oxidative stress results from the inflammatory state and can increase the risk of damage to the DNA, which can cause genetic mutations that cause normal cells to change into cancer cells (carcinogenesis). Dysbiosis can disrupt the cellular pathways that control the way cells grow and divide, which can cause cancer cells to grow and can affect the way the body eliminates abnormal and potentially carcinogenic cells, called apoptosis. 

Disruptions in the microbiome can increase the production of cancer-promoting hormones and metabolites that can increase the risk of certain cancers. Bacterial metabolites are produced by bacteria as they break down various substances, mainly through our diet. Some of these metabolites can have a cancer-protective effect, such as short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate. These SCFAs are produced when microbes in the gut ferment dietary fiber. 

SCFAs have been found to help maintain the integrity of the gut barrier and have anti-inflammatory and anti-cancer properties. Many other bacterial metabolites, such as heterocyclic amines, nitrosamines, lithocholic acid, and deoxycholic acid, have been shown to increase inflammation, promote DNA damage, and increase the risk for carcinogenesis.

Gut Microbiome and Gastrointestinal Cancers

Recent research has established a link between the gut microbiome and various gastrointestinal (GI) cancers, including colorectal (CRC), gastric, esophageal, liver, and pancreatic. This connection, termed the gut-cancer axis, delineates the intricate relationship between the health of the gut microbiome and the onset, prevention, and treatment of GI cancers. The GI tract contains 60-80% of the body's immune cells. Dysbiosis triggers inflammation, DNA damage, and immune response alterations, contributing significantly to carcinogenesis as well as disease progression and increasing overall mortality. 

There is a strong linkage between inflammation and GI cancers, as is seen with the increased risk for GI cancers in people with inflammatory bowel disease (Crohn’s and ulcerative colitis). CRC has been linked to lifestyle choices such as diet (increased red and processed meat and low fiber), smoking, alcohol consumption, and sedentary lifestyles. When these factors are combined with gut dysbiosis, a perfect storm is created to increase the risk for carcinogenesis. Patients with CRC have been found to have increased strains of microbes such as Fusobacterium nucleatum, colibactin-producing Escherichia coli, and enterotoxigenic Bacteroides fragilis as well as secondary bile acids when compared to healthy people without CRC. 

Researchers are also exploring certain microbes like Actinobacteria, Proteobacteria, and Firmicutes for their potential anti-carcinogenic properties. Additionally, substances such as SCFAs, nicotinic acid, linoleic acid, and fructose have been shown to have significantly lower levels in the stool of CRC patients compared to those without CRC. These findings are promising and may be able to influence earlier detection of GI cancers, improved treatments, and increased overall survival. 

The Oral Microbiome's Cancer Associations

The oral microbiota is another emerging area of research in the oncology field. The oral cavity hosts more than 700 different species of microorganisms. Oral health has been linked to many disease conditions, including many cancers. The oral microbiome is influenced by our oral hygiene techniques as well as diet, tobacco, alcohol, medications, genetics, chronic medical conditions, age, and hormones. 

Poor oral hygiene can increase the risk of dental plaque. If the plaque is not removed, pathologic bacteria proliferate and cause gingivitis and inflammation of the gums. Left untreated, this can progress to periodontal disease (PD). PD can damage the bones and other tissues in the mouth, produce harmful toxins, and trigger an inflammatory response. Studies have found that people with periodontal disease are two to five times more likely to develop cancer than people with healthy oral microbiomes. 

Porphyromonas gingivalis and Fusobacterium nucleatum are pathogens that are associated with periodontal disease and have been associated with some oral cancers, mainly oral squamous cell carcinoma as well as esophageal adenocarcinoma. Other areas of research include the impact of viruses such as human papillomavirus and Epstein-Barr virus and fungal infections such as candida albicans and their effect on the microbiome and carcinogenesis. Lactobacillus strains are being studied for possible protective benefits. 

The Role of the Microbiome in Cancer Treatment Efficacy

The gut microbiome is being studied to determine its influence on the cancer treatment response, mainly the efficacy and toxicity of chemotherapeutic and immunotherapeutic agents. Researchers are finding that the composition of the microbes in the gut can influence how the immune system responds to cancer cells and the ability to tolerate treatments. 

Patients with a healthy microbiome profile have been found to respond better to cancer treatments, have fewer side effects, and have improved outcomes than patients with imbalanced microbiomes. Chemotherapy and immunotherapies are often administered with antibiotics and steroids to alleviate side effects. These medications, along with cancer therapies, increase the likelihood of dysbiosis. This increases side effects and may potentially worsen treatment outcomes. 

Researchers have been exploring methods to modulate the microbiome for improved therapeutic responses. Strategies such as dietary interventions, pre and probiotic supplements, and fecal microbiota transplantation (FMT) are currently being investigated. FMT, in the oncology setting, is the process of transferring fecal matter from a person with a healthy microbiome who has responded well to the cancer treatment into the GI tract of a person undergoing cancer treatment. It is hopeful that these interventions will allow the development of treatments that are tailored to individuals to improve their outcomes and quality of life.

Functional Medicine Lab Testing: Microbiome Analysis

Functional medicine providers often incorporate laboratory testing to identify root causes of symptoms and/or disease as well as to provide insight into strategies to decrease the risk of diseases. The results of the studies can help functional medicine providers create unique treatment plans that are tailored to the individual. 

Comprehensive stool analysis is essential to evaluate the health of the microbiome and the overall functioning of the GI system in cancer patients. Stool testing is commonly used to evaluate the microbiome for signs of dysbiosis, inflammation, immune function, metabolites, and diversity. There are many tests available, each with unique methods of evaluating the microbes as well as the biomarkers that they are assessing. 

The GI-Effects Profile by Genova Diagnostics is very popular among functional providers to evaluate the cause of many GI symptoms. GI Effects results will provide information on the health of the microbiome, including measures of inflammation, immunology, and metabolic health. SCFAs are measured, as well as Calprotectin, which is a potential biomarker for CRC. Zonulin can be added on to evaluate for intestinal permeability. 

The Microbiomix test by Genova Diagnostics can be ordered as a stand-alone test or as an add-on to the GI Effects Comprehensive profile. It is a more extensive evaluation of the microbiome, measuring over 28,000 species of microbes, including a report on the metabolites present in the microbiome as well as a measure of the diversity of the microbiome. The GI-MAP + Zonulin stool test by Diagnostic Solutions evaluates the microbiome for dysbiosis, pathologic microbes, immune function, signs of inflammation, digestion, and absorption. This test assesses for H Pylori, which has been linked to stomach cancer. A functional medicine provider can test for Zonulin to assess intestinal permeability or "leaky gut.”

Aside from stool testing, functional medicine providers may consider the Oxidative Stress 2.0 Urine by Genova Diagnostics, which measures two biomarkers of oxidative stress, including Lipid Peroxides and 8-OHdG. Increased oxidative stress secondary to free radicals can increase the risk for cancer through DNA damage. 

Probiotics, Prebiotics, and Cancer Prevention

Pre and probiotics have been studied for their possible role in cancer risk modulation. Probiotics are the living strains of microorganisms that are essential in creating healthy gut microbiomes. They can be obtained through food sources, such as fermented foods like sauerkraut, yogurt, kefir, or kimchi, or in a supplement form via pills, capsules, powders, or liquids. 

Some probiotic strains that have been found to be beneficial in the cancer setting are Lactobacillus acidophilus, Streptococcus, Bifidobacterium, Propionibacterium, and Enterococcus, as well as beneficial yeasts such as Saccharomyces boulardii. The potential role of prebiotics in cancer prevention has also been researched. 

Prebiotics are undigestible plant fibers that “feed” the probiotic microorganisms and allow them to proliferate. Examples include inulin (found in onions, garlic, chicory root, asparagus, and Jerusalem artichoke), galacto-oligosaccharides (chickpeas, lentils, nuts, and some dairy products), fructo-oligosaccharides (garlic, onions, bananas, and some grains), and some starches. There is growing evidence to support the beneficial effects of pre and probiotics in cancer risk modulation. They have been found to help decrease the proliferation of cancer cells, induce apoptosis in cancer cells, decrease inflammation, and produce compounds, such as SCFAs, that have anticancer activity towards certain carcinogens and other toxicities in the gut. 

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The Microbiome and Cancer: Key Takeaways

Advancing cancer research through microbiome studies is an emerging area of research with promising links between the health of the microbiome and the development of cancer. While associations have been found between the microbiome and cancer, researchers are still evaluating whether unhealthy microbiomes can cause cancer or if the microbiome becomes unhealthy after people have developed a cancerous process. Further large-scale human studies are needed to evaluate this. Improved outcomes have been associated with a healthy microbiome. It is important for providers to include testing of the microbiome into their treatment plans and to encourage diets rich in pre and probiotics.