The Aging Gut Microbiome in Ovarian Cancer

Age-related changes to the gut microbiome are well-documented and have been shown to differ in healthy or unhealthy aging. It is also known that the gut microbiome is affected by ovarian cancer and can make a difference in treatment response and outcomes. However, there is currently no published original research on the gut microbiome in aging and ovarian cancer together. This dissertation addressed this need with a review of the literature on the gut microbiome in aging and ovarian cancer followed by four chapters of original research on the topic. The tumor studies presented here consist of murine models of ovarian cancer metastasis effected via intraperitoneal injection of syngeneic ovarian cancer cells into immunocompetent mice, modulating the gut microbiome before and/or during tumor growth. While aged mice in this model system consistently have higher tumor burden than their young counterparts, the studies presented here showed several effects of gut microbiome modulation. Aged mice cohoused with young mice had lower tumor burden than aged mice housed only with other aged mice and aged mice given fecal microbiota transplant (FMT) from tumor-naïve donor mice without contacting the donors exhibited attenuated tumor growth compared to aged mice given only saline vehicle. It was also noted that aged mice responded best when given FMT from aged rather than young donor mice, and that tumor burden was particularly reduced in the mesentery. 16S sequencing data showed that tumor reduction was accompanied by increases in gut species to young-like levels in the cohousing study, that FMT from either age of donor was effective at rendering the recipient’s gut microbiome remarkably similar to that of the donor, and that increased phylogenetic diversity in aged mice treated with FMT corresponded to lower tumor burden. These findings set a precedent for future research on the translation of age-tailored gut microbiome modulation to the clinic as a supplement to ovarian cancer treatment.