Influences of Gastrointestinal Microbiota Dysbiosis on Serum Proinflammatory Markers in Epithelial Ovarian Cancer Development and Progression

SIMPLE SUMMARY: Advanced epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer due to the lack of available early screening methods that are available in clinical settings. Unique gastrointestinal (GI) microbiota have been detected in the ovaries and peritoneal fluid of women with EOC that are not found in women without disease. However, there are limited data available to determine possible links in GI microbiota composition and early ovarian cancer development while women are largely asymptomatic. This research utilizes an EOC animal model to investigate the effects of GI microbial disruption on systemic inflammation during early disease development and progression. The identification of distinct GI microbial communities that may potentially mediate systemic immune response during carcinogenesis can open new opportunities to disentangle the complex ovarian tumor microenvironment for the discovery of valid clinical tools for early EOC detection. ABSTRACT: GI microbiota has been implicated in producing the inflammatory tumor microenvironment of several cancers. Women with ovarian cancer often report GI-related symptoms at diagnosis although minimal is known about the possible GI bacteria that may trigger pro-tumorigenic immune responses in early EOC. The purpose of this study was to investigate the influences of GI microbiota dysbiosis on serum inflammatory markers during EOC utilizing a rodent model. This experimental design consisted of C57BL/6 mice randomly assigned to either the microbiota dysbiosis group (n = 6) or control group (n = 5). The CD7BL/6 mice assigned to the microbiota dysbiosis group were administered a mixture of broad-spectrum antibiotics (bacitracin and neomycin) for 2 weeks. Both groups were injected intraperitoneally with mouse ovarian epithelial cells that induce ovarian tumorigenesis. Levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were assessed in the serum, and the composition of the GI microbiota in fecal samples was measured using 16S rRNA gene sequencing. Overall CRP serum levels were significantly lower and TNFα levels were significantly higher in the microbiota dysbiosis group compared to the control group. The abundances of microbiota that correlated with CRP serum levels in the combined groups were genus Parabacteroides, Roseburia, and Emergencia and species Ruminococcus faecis, Parabacteroides distasonis, Roseburia Faecis, and Emergencia timonensis. This study provides evidence to support for further investigation of the GI microbial profiles in patients at risk of EOC.