Background: Multimorbidity of intestinal cancer (IC), type 2 diabetes (T2D) and obesity is a complex set of diseases, affected by environmental and genetic risk factors. High-fat diet (HFD) and oral bacterial infection play important roles in the etiology of these diseases through inflammation and various biological mechanisms. Methods: To study the complexity of this multimorbidity, we used the collaborative cross (CC) mouse genetics reference population. We aimed to study the multimorbidity of IC, T2D, and obesity using CC lines, measuring their responses to HFD and oral bacterial infection. The study used 63 mice of both sexes generated from two CC lines (IL557 and IL711). For 12 weeks, experimental mice were maintained on specific dietary regimes combined with co-infection with oral bacteria Porphyromonas gingivalis and Fusobacterium nucleatum, while control groups were not infected. Body weight (BW) and results of a intraperitoneal glucose tolerance test (IPGTT) were recorded at the end of 12 weeks, after which length and size of the intestines were assessed for polyp counts. Results: Polyp counts ranged between 2 and 10 per CC line. The combination of HFD and infection significantly reduced (P <.01) the colon polyp size of IL557 females to 2.5 cm2, compared to the other groups. Comparing BW gain, IL557 males on HFD gained 18 g, while the females gained 10 g under the same conditions and showed the highest area under curve (AUC) values of 40 000-45 000 (min mg/dL) in the IPGTT. Conclusion: The results show that mice from different genetic backgrounds respond differently to a high fat diet and oral infection in terms of polyp development and glucose tolerance, and this effect is gender related.
Bibliographical noteFunding Information:
The present work is part of an MSc thesis by Asal Milhem. The authors declare no competing financial interests or other associations that may pose a conflict of interest (eg pharmaceutical stock ownership, consultancy). This report was supported by Binational Science Foundation (BSF) grant number 2015077, German Israeli Science Foundation (GIF) grant I‐63‐410.20‐2017, Israeli Science Foundation (ISF) grant 1085/18 and core fund form Tel‐Aviv University. The authors thank Ms Yasmeen Iraqi for her comments and suggestions on the report.
© 2021 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.
- high-fat diet (42% fat)
- intestinal cancer
- oral bacterial infection
- type 2 diabetes (T2D)