Could fecal microbial transplantation offer a new potential in the treatment of metastatic pancreatic ductal adenocarcinoma?

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to its aggressiveness and resistance to anti-cancer medications. Recent data suggest that solid tumors such as PDAC are infected with microbial agents, which can induce aggressive phenotype and metabolize chemotherapeutical agents. However, it was shown that gut microbiota can migrate to the pancreas and that fecal microbial transplantation (FMT) from long-term PDAC survivors can alter both gut and tumor microbiome, the immune response, and the growth of PDAC in a murine model.Although the effect of FMT on enhancing the immune response was exhibited in melanoma patients, there is no robust data to support the use of immunotherapy in the majority of PDAC patients, as chemotherapy remains the mainstay of treatment. Along with its direct cytotoxic effect, chemotherapy can also reduce ineffective cytokine sinks via lymphodepletion and increase translocation of the gut microbiota leading to stimulation of the immune response. However, chemotherapy requires a functional microbiota to exert those effects.We hypothesize that altering the microbiome with the FMT from the long-term PDAC survivors, combined with systemic treatment, can potentially enhance the relationship between chemotherapy, the immune system, and the microbiome. Albeit there is a lack of knowledge regarding the exact composition of the ideal donor microbiome and the optimal patient selection, due to the dismal prognosis of PDAC patients, such a trial could offer a low-risk, high-reward situation.