Microbial Correlates of Changes In Colon Prostaglandin E2 In Humans: Role Of Mucinophilic Bacteria

Abstract

Prostaglandin E2 is a pro‐inflammatory mediator in the colon that is tightly linked with risk of colon cancer. We conducted a dietary intervention trial aimed at reducing colon prostaglandin E2 in subjects who had an increased risk of colon cancer. Subjects were randomized to a Healthy Eating or a Mediterranean diet for six months. Biopsies of the colon were obtained before and after dietary intervention, without prior preparation of the bowels. Two colon biopsies from each subject were analyzed for concentrations of eicosanoids, and an additional, nearby, biopsy was subjected to 16s sequencing to identify the bacterial taxa adhering to the mucin layer. Data was available for 85 subjects at baseline, and 67 subjects had complete data at both time points. There were few changes in eicosanoids and microbial taxa after dietary intervention. Since the diets were self‐selected and different individuals met their macronutrient dietary goals using different foods, we conducted correlative studies of prostaglandin E2 with adherent taxa at baseline as well as studies of changes over time. We focused on mucinophilic bacteria that can degrade both fiber and mucin. It has been previously demonstrated in many studies that Akkermansia mucinophilia is associated with beneficial, anti‐inflammatory effects on the host as well as protection from intestinal tumors in mice. At baseline, the relative abundance of Akkermansia mucinophilia and the abundance of total Verrucomicrobia taxa (Akkermansia and three other taxa) was negatively correlated with expression cyclooxygenases‐1 and 2 which catalyze synthesis of prostaglandin E2. The relative abundance of Verrucomicrobia and Akkermansia was also negatively correlated with serum cytokines, indicating a relationship with systemic inflammatory status (p<0.03). Change in prostaglandin E2 concentration over 6 months in the colon was significantly and negatively correlated with change in abundance of Akkermansia mucinophilia and Verrucomicrobia (p<0.02 in each case). The dietary factor that appeared to be most influential on changes in Akkermansia mucinophilia and Verrucomicrobia was total saturated fat intake, which was correlated negatively. Fiber intake notably had a weaker influence on the abundance of Akkermansia mucinophilia or Verrucomicrobia in the colon biopsies. These results show the potential influence of the bacterial populations adhering to the mucus layer of the colon on the inter‐individual variation in colonic epithelial prostaglandin E2.Support or Funding InformationSupported by NIH grant CA120381, Cancer Biology Training Grant 5T32CA009676, and Cancer Center Support Grant P30 CA046592