Introduction:
The human body contains a vast number of microorganisms that influence cancer risk, partly due to their significant metabolic abilities and impact on immune cells. Around 15 to 20 percent of cancer cases are linked to microbial infections. Additionally, some malignancies can occur due to dysbiosis, which involves changes in the friendly microbiome. Controlled experiments have shown that the microbiome can indeed affect cancer development and progression through various mechanisms, including inflammation, causing DNA (deoxyribonucleic acid) damage, and producing substances that can either promote or inhibit tumor growth.
Research also suggests that manipulating the microbiome can aid in cancer treatment by enhancing checkpoint inhibitors (a type of immunotherapy) using probiotics (live organisms that can provide benefits to the health) and developing drugs that can target microbial enzymes.
What Is the Human Microbiome?
The microbiome is a collection of microorganisms such as viruses, bacteria, fungi, and archaea (single-celled microorganisms) that reside in and on the human body, impacting health and diseases. The gut microbiome plays a crucial role in metabolism, digestion, and immune function, and it also influences treatments like cancer. Long-term dietary habits have a more significant impact than short-term changes, and lifestyle factors also affect the microbiota. Some microbial pathogens not only coexist but also contribute to certain cancers; for example, H. pylori (Helicobacter pylori) is associated with gastric adenocarcinoma (a type of cancer that originates from the stomach lining) due to induced inflammation and gastritis, but it also protects against esophageal adenocarcinoma (a type of cancer that develops in the lower part of the esophagus) by influencing stomach pH and reducing acid reflux. The relationship between cancer and microbes is complex, involving factors such as genetic variations, environmental influences, dietary changes, lifestyle choices, and chronic inflammation (a main risk factor).
What Are the Effects Of Microbiome in Tumor Suppression and Oncogenesis?
The commensal bacteria have a crucial impact on cancer through their metabolic effects on immune cells and inflammation. The gastrointestinal tract, which houses most of the bacteria, plays a vital role in nutrient absorption, metabolism, and immune cell development. The effects of the gut microbiome on tumor promotion include:
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Production of oncometabolites such as hydrogen sulfide.
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Impairment of barrier function, leading to exposure of immune cells to bacterial antigens and endotoxins (bacterial toxin).
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Direct effects of bacterial antigens and metabolites on immune cells, causing hyperactivation and inflammation.
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The presence of virulence factors (a specific factor or molecule that enhances the ability of the microorganism to cause negative effects on the host) in bacteria can cause DNA damage.
On the other hand, the effects of the gut microbiome as tumor suppressive include:
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Production of tumor suppressive metabolites like butyrate.
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Maintenance of barrier function.
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Modulating immune cells to prevent inflammation.
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Reducing the immune response through immunosuppressive cytokines.
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Competitive removal of pathogenic microorganisms, preventing C. difficile (Clostridium difficile) infections that cause gastrointestinal disorders.
The gut microbiome can also have distal effects on cancer, which can be either tumor-suppressive or tumor-promoting through the circulation of microbial metabolites, microbiota, or promotion/suppression of immune cells.
What Is the Influence of Microbiome on Cancer Treatment?
According to some studies, microbiota plays a role in modifying how the body responds to various anticancer drugs. One of the primary mechanisms underlying these different responses is immunomodulation, which involves modifying the immune activity. For instance, in patients undergoing allogeneic hematopoietic stem cell transplants (allo-HSCT) for the treatment of hematopoietic malignancies (blood cancers), increased diversity of gut microbiota has been associated with decreased mortality rates. However, it's important to note that this increased diversity can also be responsible for some side effects.
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Immunotherapy
The immune system plays a crucial role in identifying and destroying cancer cells, with T lymphocytes being central to this response. T-cell activation relies on co-inhibitory signals from molecules like PD-1 (programmed cell death-1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) on antigen-presenting cells. FDA (food and drug administration)-approved drugs called immune checkpoint inhibitors (e.g., Ipilimumab, Nivolumab, Pembrolizumab) activate the body's immune system to fight tumors.
The effectiveness of these drugs is influenced by the gut microbiome. Numerous studies have shown that the response to immune checkpoint inhibitors is related to the gut microbiota, and altering the microbiome improves the anti-tumor response rate. However, the side effects of these inhibitors depend on the environment, genetics, and microbiota. Nevertheless, the gut microbiota plays a significant role in the response to immune checkpoint inhibitors and cancer treatment.
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Chemotherapy
Chemotherapy can indeed alter the microbial community, although its impact remains somewhat unclear. However, specific compositions of gut microbiota have been found to influence the response to chemotherapy. In the case of the platinum chemotherapeutic Oxaliplatin, its effectiveness relies on the presence of gut microbiota, which plays a crucial role in producing ROS (reactive oxygen species). ROS production by microbiota is essential for tumor regression. Researchers are currently conducting further studies to optimize the microbiota by identifying specific microorganisms that can improve chemotherapy in cancer treatment. This research holds promise for improving cancer therapies in the future.
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Microbial drug target
Microbial drug targets are specific components within microorganisms that can be targeted by therapeutic agents or drugs to kill the microorganism. By disrupting these essential processes, the microorganism's destruction can be achieved, and these targets may also help reduce the side effects of chemotherapeutic agents on the gastrointestinal (GI) tract. For example, the drug Irinotecan, used to treat pancreatic and colorectal cancer, can cause severe diarrhea due to its impact on gut microbiota. However, lacking gut microbiota can lead to less GI damage and increased tolerance to higher doses of Irinotecan. Ongoing studies are exploring the use of antibiotics to inhibit bacterial enzymes that cause damage to the GI tract. Targeting microbiota holds promise in reducing the toxicities caused by chemotherapeutic agents and improving the effectiveness of cancer treatments.
Conclusion:
The role of the human microbiome in cancer treatment is rapidly advancing in oncology. Gut microbiota plays a significant role in cancer development. Consuming a fiber-rich diet and prebiotics can help protect against cancer. Engineered probiotic bacteria using gene-editing technologies can also counteract cancer-promoting factors. Genetic screenings of host-microbiome interactions contribute to cancer research.
