Are Changes in the Gut Microbiome Associated with the Development of Cancer?
PREMIUM CONTENT for MEMBERS ONLY
In recent years, there has been an exponentially growing interest in the impact of the gut microbiome on human health and disease. The microbiome has been linked to many physiological processes in health and disease, including the development and progression of cancer.
“…comparing the microbiomes of individuals with and without cancer does not prove causation.”
Despite the enthusiasm amongst patients, researchers and clinicians about the emerging research findings, comparing the microbiomes of individuals with and without cancer does not prove causation. In other words, it is unknown whether microbiota changes are a cause or consequence of cancer. Future research is needed to understand the exact mechanisms at play between cancer and the microbiome, but the associations and early discoveries are fascinating.
Cancer develops when abnormal cells grow out of control, forming lumps of tissue called tumors. The normal process of cell division makes more mistakes than you would expect, and in most cases, the immune system is able destroy damaged cells or small tumors before they become cancerous by recognizing molecules on the surface of these dangerous cells. However, the tumor microenvironment (TME) introduces mechanisms for tumors to develop and escape defense mechanisms from the immune system, and inhibits the immune system from recognizing them as dangerous through eliminating antigen recognition.
“…the second half of the small intestine and the large intestine harbors some 100 trillions of microbial organism and more than 70% of our immune cells…”
The gut microbiota and the immune system have close interactions, known as the gut-immune connection. The gastrointestinal tract, in particular the second half of the small intestine and the large intestine harbors some 100 trillions of microbial organism and more than 70% of our immune cells, making it la promising target for the development of new cancer treatments. The cancer-modulating effects of microbiota are associated with dysbiotic microbiomes, pathogenic carcinogens, gut-derived metabolites, and interactions of cell wall components of microbes (such as lipopolysaccharides, or LPS) with gut based immune cells.
“Dysbiosis is characterized by low microbial diversity and richness, and reduced populations of beneficial microbes producing anti-inflammatory molecules, as well as a compromised intestinal barrier…”
As discussed many times in this newsletter and in Dr. Mayer’s book, The Mind Gut Immune Connection, factors such as use of antibiotics, an inflammatory, ultra-processed diet, and aging contribute to dysbiosis. Dysbiosis is characterized by low microbial diversity and richness, and reduced populations of beneficial microbes producing anti-inflammatory molecules, as well as a compromised intestinal barrier allowing microbes coming in contact with the gut-based immune system. This dysbiosis also compromises the microbiome’s ability to protect itself from the invasion of foreign pathogenic organisms. This may lead to chronic inflammation, where overtime there are higher risks of tumor onset due to DNA damage, genetic instability, and the formation of a tumor.
Of the estimated one trillion microbial species on Earth, 11 are carcinogenic, causing around 13% of global cancer cases. In such cases, infection by a certain bacterial pathogen directly drives the development of a tumor. An example of this is seen in gastric cancer, which is triggered by certain strains of the microbial organism H. pylori. These pathogenic H. pylori strains produce a toxin called CagA proteins. CagA that gets injected into the junctions where cells of the stomach lining meet. Once inside cells, CagA can cause them to become cancerous by removing controls on cell growth. Long-term exposure of cells to the toxin causes chronic inflammation of the stomach lining making it the strongest risk factor for the development of gastric cancer.
“…carcinogenesis can also be triggered by dysbiosis resulting in chronic immune activation and harmful gut-derived metabolites.”
While bacteria such as H. pylori may be a strong culprit for the development of gastric cancer, carcinogenesis can also be triggered by dysbiosis resulting in chronic immune activation and harmful gut-derived metabolites. Metabolites are natural products that are created after bacterial metabolic processes, Colibactin, a metabolite produced by E. coli, prevents strands of the double helix of DNA from linking, causing DNA strand breakage and unstable intestinal epithelial cells, ultimately leading to colorectal cancer.
While the links between the gut microbiome and cancer are becoming clearer, the causation remains elusive. The fascinating interplay of dysbiosis, carcinogenic microbes, chronic activation of the gut-associated immune system leading to metabolic endotoxemia and gut-derived metabolites underscores how chronic alterations in the gut microbiome can contribute to the development of gastrointestinal cancers. On the other hand, the ability of beneficial microbial strains to generate anti-inflammatory short chain fatty acids and to improve the mucus lining of the gut are mechanisms to protect against the development of cancer. Adhering to a gut healthy diet as described in Dr. Mayer’s new recipe book Interconnected Plates is a simple way to make the gut microbiome a partner in fighting chronic diseases like cancer.