Type 2 diabetes (T2D) is a
metabolic disease with an imbalance in
blood glucose concentration. There are significant studies currently showing association between T2D and
intestinal cancer developments. High-fat diet (HFD) plays part in the disease development of T2D,
intestinal cancer and
infectious diseases through many biological mechanisms, including but not limited to
inflammation. Understanding the system genetics of the multimorbidity of these diseases will provide an important knowledge and platform for dissecting the complexity of these diseases. Furthermore, in this study we used some machine learning (ML) models to explore more aspects of
diabetes mellitus. The ultimate aim of this project is to study the genetic factors, which underline T2D development, associated with
intestinal cancer in response to a HFD consumption and oral
coinfection, jointly or separately, on the same host genetic background. A cohort of 307 mice of eight different CC mouse lines in the four experimental groups was assessed. The mice were maintained on either HFD or chow diet (CHD) for 12-week period, while half of each dietary group was either coinfected with oral bacteria or uninfected. Host response to a
glucose load and clearance was assessed using intraperitoneal
glucose tolerance test (IPGTT) at two time points (weeks 6 and 12) during the experiment period and, subsequently, was translated to area under curve (AUC) values. At week 5 of the experiment, mice of group two and four were coinfected with Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) strains, three times a week, while keeping the other uninfected mice as a control group. At week 12, mice were killed, small intestines and colon were extracted, and subsequently, the
polyp counts were assessed; as well, the intestine lengths and size were measured. Our results have shown that there is a significant variation in
polyp's number in different CC lines, with a spectrum between 2.5 and 12.8 total
polyps on average. There was a significant correlation between area under curve (AUC) and intestine measurements, including
polyp counts, length and size. In addition, our results have shown a significant sex effect on
polyp development and
glucose tolerance ability with males more susceptible to HFD than females by showing higher AUC in the
glucose tolerance test. The ML results showed that classification with random forest could reach the highest accuracy when all the attributes were used. These results provide an excellent platform for proceeding toward understanding the nature of the genes involved in resistance and rate of development of
intestinal cancer and T2D induced by HFD and oral
coinfection. Once obtained, such data can be used to predict individual risk for developing these diseases and to establish the genetically based strategy for their prevention and treatment.