Written by Lisa Liong '25
Edited by Surya Khatri '24
In the quest for new cancer treatments, an unlikely candidate has emerged: fecal transplantations.
Recent studies have implicated fecal transplants as a potential treatment for cancer due to their unique influence on the gut microbiome [1]. The gut microbiome is composed of trillions of bacteria, fungi, and other microscopic organisms referred to as microbes. This complex system of microbes mostly resides in the large intestine and plays an important role in improving digestion, immune function, and brain health. Diversity amongst microbes in the gut microbiota is linked to better health. Common cancer treatments, such as chemotherapy and radiation, do not differentiate between killing cancer cells and beneficial bacterial cells in the gut. They can kill off the beneficial and harmful bacteria in the gut microbiome, which impairs the body’s ability to fight infections [2].
The composition of the gut microbiome influences the responses of cancer patients to immunotherapy, a cancer treatment that employs the body’s immune system to identify and fight cancer cells. However, some cancer patients do not respond to immunotherapy drugs. Studies suggest that the gut microbiome plays a large role in how patients respond to certain drugs, which gave rise to the novel idea of using fecal transplants as a potential cancer treatment [1].
During a fecal microbiota transplantation (FMT), stool samples from a healthy donor are moved to a sick patient to repopulate a patient’s gut with healthy bacteria. FMT has been widely used to treat Clostridium difficile (C. diff), a severe infection that leads to diarrhea and colon inflammation. It is a safe and effective treatment that has been used to treat C. diff since 2013 [3], but new research has implicated FMT as a potential cancer treatment.
A recent paper tracked advanced melanoma patients’ response to a type of immunotherapy drug called a PD-1 inhibitor. PD-1 is a checkpoint protein on T-cells, a type of immune cell. It functions as an “off switch” by binding to PD-L1, a protein on cells, to prevent T cells from attacking the cell. However, some cancer cells express high levels of PD-L1, which allow them to escape detection by T-cells that would normally attack tumors. Anti PD-1 drugs work by blocking PD-1 on T-cells, which inactivates the mechanism that some tumor cells use to avoid detection by T-cells. This then allows T-cells to recognize and attack tumor cells, which harnesses the body’s immune system in fighting cancer [4].
The paper found that some cancer patients who did not initially respond to immunotherapy saw their tumors stop growing or shrink after receiving a stool sample from a patient for whom immunotherapy worked. FMT changes the gut microbiome and the tumor’s environment to overcome resistance to immunotherapy drugs. Patients who responded to fecal transplantation saw greater diversity in their gut microbiomes. The bacterial composition of their microbiomes shifted to resemble the donor’s composition. Scientists theorize that certain gut microbiome environments prime T-cells for immunotherapy, but the mechanism by which the microbiome influences cancer treatment is unknown [5].
This paper is one of many papers related to the growing field of gut microbiome research. The gut microbiome plays an important role in maintaining health, and the mechanisms for these functions are still poorly understood. While previous papers have focused on characterizing the gut microbiome, newer studies are finding unexpected ways to utilize the gut microbiome to improve human health. Although this treatment is very new, it holds promise for patients with immunotherapy-resistant tumors. Further clinical studies need to be done to test the safety and efficacy of this novel treatment, but fecal transplantations may very well become an important cancer treatment in the future.
References
[1] Kaiser J. Your gut bacteria could determine how you respond to cutting-edge cancer drugs. Science [Internet]. 2017 [cited 2022 Mar 20]; Available from: https://www.science.org/content/article/your-gut-bacteria-could-determine-how-you-respond-cutting-edge-cancer-drugs
[2] Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J [Internet]. 2017 [cited 2022 Mar 20];474(11):1823–36. Available from: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5433529/
[3] Leininger A. Fecal microbial transplantation [Internet]. Hopkinsmedicine.org. 2017 [cited 2022 Mar 20]. Available from: https://www.hopkinsmedicine.org/johns-hopkins-childrens-center/what-we-treat/specialties/gastroenterology-hepatology-nutrition/procedures/fecal-microbial-transplantation.html
[4] Immune Checkpoint Inhibitor [Internet]. National Cancer Institute. 2011 [cited 2022 Mar 20]. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/immune-checkpoint-inhibitor
[5] Davar D, Dzutsev AK, McCulloch JA, Rodrigues RR, Chauvin J-M, Morrison RM, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science [Internet]. 2021;371(6529):595–602. Available from: http://dx.doi.org/10.1126/science.abf3363
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