Studying host genetic background effects on multimorbidity of intestinal cancer development, type 2 diabetes and obesity in response to oral bacterial infection and high‐fat diet using the collaborative cross (CC) lines

Abstract

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.

High‐fat diet and oral infection induced type 2 diabetes and obesity development under different genetic backgrounds

“…Regarding AUC in the early phase after infection (week 6), in both sexes, on CHD, higher blood glucose level was observed in the noninfected group than in the infected group, also proposed by Milhem et al, 52 whereas on HFD, higher blood glucose level was observed in the infected group than in the noninfected group. A positive Δ value indicated a slow glucose tolerance status, which could lead to the conclusion that the infection caused slow and acceleration of diabetes in mice as observed in infection of prediabetic NOD mice, although in type 1 diabetes 53 …”

Potential role of gut microbiota-LCA-INSR axis in high fat-diet-induced non-alcoholic fatty liver dysfunction: From perspective of radiation variation

“…However, F. nucleatum also has an anti-inflammatory role through the production of butyric acid ( Stokowa-Soltys et al, 2021 ). Asal Milhen et al found that mice fed a HFD diet had an increased F. nucleatum abundance, with increased body weight and glucose tolerance ( Milhem et al, 2021 ). Another study found a causal link between the activation of the LPS pathway by F. nucleatum and HFD-induced inflammation ( Blasco-Baque et al, 2012 ).…”

Towards system genetics analysis of head and neck squamous cell carcinoma using the mouse model, cellular platform, and clinical human data

“…123 The strategy for generating system genetics data and pheno- In order to comprehend the pathophysiology, transmission, and host immune response to infection, animal models are essential. 128 Furthermore, the development and testing of medicinal drugs and vaccines depend heavily on animal models. 129 Before choosing an animal model to study an infectious agent, the scientific team must first decide if there is enough ex vivo and in vitro data available to support conducting research into an animal model, if ethical issues are taken care of, and if the data obtained from animal work will contribute meaningfully to the body of scientific knowledge.…”

“…In order to comprehend the pathophysiology, transmission, and host immune response to infection, animal models are essential 128 . Furthermore, the development and testing of medicinal drugs and vaccines depend heavily on animal models 129 .…”