Objective: We aimed to analyze the mechanisms underlying spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction derived from the trimethylamine N-oxide (TMAO) metabolic pathway of intestinal microbiota in the treatment of macrovascular lesions caused by type 2 diabetes mellitus (T2DM).
Methods: Hartley-guinea pigs were randomly divided into 3 groups—the blank, model, and intervention groups. The T2DM combined with atherosclerosis guinea pig models were established in the model and intervention groups. After successful modeling, spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction were administered intragastrically to the intervention group, while the same volume of normal saline was administered via gavage to the blank and model groups. After 6 weeks of continuous gavage, guinea pigs were sacrificed in all groups, the colon contents were obtained, and the diversity and structural differences of intestinal microbiota were analyzed via bioinformatics. Serum was collected to detect differences in lipids, TMAO, oxidative stress, and inflammation markers between groups.
Results: Compared to the blank group, the species diversity of the intestinal microbiota in the model and intervention groups was significantly reduced. Based on the results of Analysis of Similarities and Multiple Response Permutation Procedure, the microbiota structure of the intervention group was closer to that of the blank group. After modeling, the blood lipid levels of guinea pigs increased significantly, and drug intervention significantly reduced the levels of TC, TG, and LDL-C (P < 0.05). TMAO expression was significantly increased after modeling (P < 0.05), while drug intervention reduced TMAO expression (P < 0.05). Compared to the model group, drug intervention significantly increased the concentrations of SOD while decreasing the concentrations of MDA, ICAM-1, VCAM-1, IL-6, and hs-CRP.
Conclusion: Spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction can reduce the risk of macrovascular lesions in T2DM, and its mechanism may be associated with its ability to regulate the TMAO metabolic pathway of intestinal microbiota.

Keywords: intestinal microbiota, macrovascular lesions, spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction, trimethylamine N-oxide, type 2 diabetes mellitus