High-fat diet promotes type 2 diabetes mellitus by disrupting gut microbial rhythms and short-chain fatty acid synthesis

Diabetes ranks among the top 10 causes of death globally, with over 90% of individuals diagnosed with diabetes having type 2 diabetes mellitus (T2DM). It is acknowledged that a high-fat diet (HFD) poses a serious risk for T2DM. The imbalance of intestinal flora, mediated by HFD, can potentially exacerbate the onset and progression of T2DM. However, the impact of HFD on pathological indicators and the intestinal microbiome in the development of T2DM has not been systematically investigated. Therefore, a HFD mouse model and a T2DM mouse model were established, respectively, in this study. The role of HFD as a driving factor in the development of T2DM was assessed using various measures, including basic pathological indicators of T2DM, lipid metabolism, liver oxidative stress, intestinal permeability, levels of inflammatory factors, gut microbiota, and short-chain fatty acids (SCFAs). The findings indicated that HFD could influence the aforementioned measures to align with T2DM changes, but the contribution of HFD varied across different pathological metrics of T2DM. The impact of HFD on low-density lipoprotein cholesterol, glutathione peroxidase, malondialdehyde, and tumor necrosis factor-α did not show a statistically significant difference from those observed in T2DM during its development. In addition, regarding gut microbes, HFD primarily influenced the alterations in bacteria capable of synthesizing SCFAs. The notable decrease in SCFA content in both serum and cecal matter further underscored the effect of HFD on SCFA-synthesising bacteria in mice. Hence, this research provided a systematic assessment of HFD's propelling role in T2DM's progression. It was inferred that gut microbes, particularly those capable of synthesizing SCFAs, could serve as potential targets for the future prevention and treatment of T2DM instigated by HFD.