Effect of Metformin Treatment on Inflammatory Factors and Gut Microbial Diversity in Patients with Type II Diabetes Mellitus

Abstract

With the persistent rise in the prevalence of Type 2 Diabetes Mellitus (T2DM), traditional treatment evaluations have primarily focused on glycemic control, often overlooking the multidimensional effects of medications. As a first-line therapeutic agent, the anti-inflammatory effects and gut microbiota regulation mechanisms of metformin remain incompletely elucidated. This prospective cohort study established a metformin treatment group and a T2DM control group not receiving metformin. Using metagenomics technology, we analyzed the effects of metformin therapy on serum inflammatory markers (interleukin-6, tumor necrosis factor-α, high-sensitivity C-reactive protein) and gut microbiota diversity in T2DM patients. Results showed that after 12 weeks of intervention, the treatment group exhibited significantly reduced inflammatory markers (IL-6 ↓25.4%, TNF-α ↓18.9%, hs-CRP ↓32.7%; P<0.01) and markedly increased gut microbiota α-diversity (Shannon index ↑18.7%, Chao1 index ↑15.2%; P<0.05). Increased abundance of key bacterial genera Akkermansia (↑3.31-fold) and Faecalibacterium (↑1.87-fold) showed a significant negative correlation with inflammation resolution (*r* = -0.82). A random forest model constructed based on microbial features accurately distinguished pre- and post-intervention states (AUC = 0.89). This study confirms that metformin suppresses systemic inflammation by reshaping the gut microbiota, providing new evidence for the “microbiota-immune” regulatory mechanism.