Assessing the host genetic background effects on type 2 diabetes and obesity development in response to mixed–oral bacteria and high-fat diet using the collaborative cross mouse model

Background: Host genetic background and sex, play central roles in defining the pathogenesis of type 2 diabetes (T2D), obesity and infectious diseases. Our previous studies demonstrated the utilization of genetically highly diverse inbred mouse lines, namely collaborative cross (CC), for dissecting host susceptibility for the development of T2D and obesity, showing significant variations following high-fat (42% fat) diet (HFD). Here, we aimed to assessing the host genetic background and sex effects on T2D and obesity development in response to oral-mixed bacterial infection and HFD using the CC lines. Materials and Methods: Study cohort consists of 97 mice from 2 CC lines (both sexes), maintained on either HFD or Standard diet (CHD) for 12 weeks. At week 5 a group of mice from each diet were infected with Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) bacteria (control groups without infection). Body weight (BW) and glucose tolerance ability were assessed at the end time point of the experiment. Results: The CC lines varied (P <.05) at their BW gain and glucose tolerance ability (with sex effect) in response to diets and/or infection, showing opposite responses despite sharing the same environmental conditions. The combination of diet and infection enhances BW accumulation for IL1912, while restraints it for IL72. As for glucose tolerance ability, only females (both lines) were deteriorated in response to infection. Conclusions: This study emphasizes the power of the CC mouse population for the characterization of host genetic makeup for defining the susceptibility of the individual to development of obesity and/or impaired glucose tolerance.