The microbiome encompasses all the microorganisms and viruses that reside in a particular environment in the body. Recent research on the relationship between the gut microbiome and a person’s health has led to an increased understanding of how specific microbiota can benefit or hinder the immune response in cancer patients and an individual’s response to cancer treatment.
A new publication in Cell Systems highlights the value of understanding the connections between microbiota and cancer therapy. The study demonstrates that a bacterium associated with colorectal cancer can elicit an anti-cancer effect on tumor cells.
The researchers employed a rigorous four-way screening approach to meticulously examine the molecular-level interactions between the host, microbe, drug, and nutrient. This comprehensive screening approach identified a metabolite, 2-methylisocitrate, that was upregulated in human tumor-associated microbiota, providing a solid foundation for the study's findings.
Moreover, the study underscores the potential of 2-methylisocitrate as a therapeutic agent by demonstrating its ability to inhibit proliferative functions in various cancer models, including cell lines, three-dimensional (3D) spheroids, and a fruit fly system that mimics gut tumors. In all the cancer model systems examined, 2-methylisocitrate was found to be associated with tumor spread. Notably, the researchers also observed an association between 2-methylisocitrate and survival in the fruit fly cancer model.
When examining microbiota on a molecular level, the researchers found that 5-fluorouracil and 2-methylisocitrate work together to increase efficacy, a biological phenomenon known as "synergy." This synergy explains the enhanced efficacy of the chemotherapy.
Chemotherapies, including 5-fluorouracil, work to kill tumors by causing DNA damage in rapidly replicating cancer cells. The researchers found that 2-methylisocitrate works through distinct cellular pathways to link metabolism with DNA damage in patients undergoing chemotherapy. The study shows that 2-methylisocitrate has the potential to disrupt the metabolism in cancer cells, making them more susceptible to 5-fluorouracil.
This study underscores the profound connections between the microbiome's metabolism and tumor growth and proliferation. These findings not only deepen our understanding of cancer but also open up exciting avenues for investigation and drug development, potentially leading to novel treatments based on the metabolites of cancer-associated bacteria.
Sources: Cell Sys