(P13-046-23) Characterizing the Effects of Diet-Related Changes in Adiposity on the Gut Microbiome in the Context of Pancreatic Carcinogenesis in Mice

Objectives: To determine the effects of diet-induced changes in adiposity on the gut microbiome during pancreatic carcinogenesis.

Methods: To study the effects of diet, elevated adiposity, and the microbiome during pancreatic carcinogenesis, we fed male and female LSL-Kras^G12D/+; p48^Cre/+ mice (n = 8-10/group/sex) a diet-induced obesity (DIO) diet or a control diet (CD) until 6 months of age. Moreover, obesity-reversal mice were fed DIO until 3 months of age then switched to the CD until 6 months of age. Body composition was measured by EchoMRI. The microbiome was evaluated using 16s rRNA sequencing. Histology was used to characterize pancreatic carcinogenesis.

Results: At 6 months of age, mice fed the DIO diet had a significantly higher body weight, body fat percentage, and adipose depot weight, compared to the CD and the obesity-reversal groups. Moreover, the obesity-reversal group modulated the gut microbiome altered by DIO. For instance, the following microbes were increased by DIO and normalized to CD levels in the obesity-reversal group: (class) Firmicutes clostridia (genus) Lachnospiraceae blautia, Oscillospiracea oscillibacter, Oscillospiracea intestimonas, Lachnospiracea roseburia. Finally, DIO fed mice presented the highest degree of acinar cell loss, a marker of pancreatic carcinogenesis, while the obesity-reversal group showed less acinar cell loss percentage, closer to that observed in the CD group, although these changes did not reach statistical significance.

Conclusions: Dietary changes may mitigate the effect of increased adiposity on pancreatic carcinogenesis, in part, by modulating the microbiome.

Funding Sources: University of California, Davis and NIFA-USDA (CA-D-NUT-2397-H) to GGM