Fecal Microbiota Transplantation as a Cancer Therapeutic.

For decades, cancer research and treatment focused on the cellular level, viewing cancer as a genetic disease of cell transformation. In the era of chemotherapy and radiotherapy, studies from the second half of the 19th century suggesting an association between the microbiota and cancer were almost neglected. The main focus of the field was limited to identification of specific viruses and bacteria that may serve as direct carcinogens leading to the recognition of 7 viruses (i.e., human papillomavirus, hepatitis B virus, and Kaposi sarcoma-associated herpesvirus) and 1 bacterium (Helicobacter pylori) as human carcinogens by the International Agency for Research on Cancer (https://monographs.iarc.who.int/agents-classified-by-the-iarc/). Shortly after the publication of the first draft of the human genome project in February 2001, the Nobel laureate microbiologist Joshua Lederberg raised the question: "Is human identity all in the genes?" It took more than a decade later and the development of multiomic techniques to confirm that his answer "each one of us is a small ecological community" was correct (Lederberg J. Keynote Address: Beyond the Genome. Brooklyn Law Rev 67). This ecological notion became relevant to cancer prevention, prediction, and treatment following the immunotherapy revolution and the understanding of the metabolic and immunologic roles of the microbiota in health and disease. Recently, the microbiota was recognized as an emerging hallmark of cancer following a large body of research showing its role in tumorigenesis, treatment efficacy and toxicity, and initial data regarding the role of microbial modulation in cancer therapy (Cancer Discov 2022;12(1):31-46). In the current review, we will focus on the role of fecal microbiota transplantation, the first microbial modulation technique that is used mainly in low-complexity conditions such as recurrent Clostridium difficile infections (Aliment Pharmacol Ther 2017;46(5):479-493), as a possible cancer therapeutic. However, to better understand the suggested roles of fecal microbiota transplantation in medical oncology, we first need to understand cancer as an ecological niche and the role of the microbiota in tumorigenesis and cancer treatment, specifically immunotherapy.