Introduction: The majority of ovarian cancer (OvCa) patients are diagnosed at age 63 and die by age 70, with a disparity in cancer-related deaths between young (Y) and aged (A) patients.  Pre-clinical studies support these data, showing increased metastatic burden in A mice relative to Y; however the molecular mechanism(s) is unclear. Aging significantly modifies aspects of the host peritoneal cavity, remodels stromal protein composition and ultrastructure, alters the peritoneal immune microenvironment (both inflammatory factors and the immune cell landscape), and shifts the microbiome due to gut dysbiosis. The objective of this study was to examine whether Y and A co-housing impacts OvCa metastatic success.

Methods: Female C57/Bl6 mice were co-housed (CoH) in cages of A-CoH (20-23 mo) and Y-CoH (3-6 mo) mice together (2A-CoH+2Y-CoH), compared with cages in which all non-CoH mice were of a single age group (3A or 3Y) for 12 weeks. Mice were injected i.p. with syngeneic OvCa cells and assessed for tumor burden after 4 weeks. Immune cells and cytokines were profiled on endpoint peritoneal lavage. Feces collected before and after co-housing were subjected to 16S rRNA sequencing to determine the effects of Y/A co-housing on the gut microbiome.

Results: As previously reported, non-CoH A mice developed significantly higher tumor burden relative to Y mice.  However A-CoH mice had significantly lower tumor burden than non-CoH A counterparts. No negative effects on tumor burden in the Y-CoH mice were observed. Significant increases in several ‘beneficial’ Y-like gut bacterial species were seen in the A-CoH mice. Analysis of immune cells is ongoing.

Conclusions: As CoH mice share gut microbiota via coprophagy, these data suggest that Y-to-A fecal microbiota transplantation may positively impact OvCa outcomes in A patients.  Studies to test this hypothesis using fecal microbiota swapping in non-CoH A and Y mice are currently underway.