Gegen Qinlian Decoction (GQD), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of common metabolic diseases, including type 2 diabetes mellitus. However, the main limitation of its wider application is ingredient complexity of this formula. Thus, it is critically important to identify the major active ingredients of GQD and to illustrate mechanisms underlying its action. Here, we compared the effects of GQD and berberine, a hypothetical key active pharmaceutical ingredient of GQD, on a diabetic rat model by comprehensive analyses of gut microbiota, short-chain fatty acids, proinflammatory cytokines, and ileum transcriptomics. Our results show that berberine and GQD had similar effects on lowering blood glucose levels, modulating gut microbiota, inducing ileal gene expression, as well as relieving systemic and local inflammation. As expected, both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria, including Faecalibacterium and Roseburia, thereby attenuating intestinal inflammation and lowering glucose. Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with berberine or GQD. Moreover, concentration of serum proinflammatory cytokines and expression of immune-related genes, including Nfkb1, Stat1, and Ifnrg1, in pancreatic islets were significantly reduced after treatment. Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota. The strategy employed would facilitate further standardization and widespread application of TCM in many diseases.

葛根沁莲汤（GQD）是一种中药（TCM）方剂，长期以来用于治疗常见的代谢疾病，包括2型糖尿病。然而，其更广泛应用的主要限制是该配方的成分复杂。因此，确定 GQD 的主要活性成分并说明其作用机制至关重要。在这里，我们通过肠道微生物群的综合分析比较了 GQD 和小檗碱（GQD 的一种假设的关键活性药物成分）对糖尿病大鼠模型的影响、短链脂肪酸、促炎细胞因子和回肠转录组学。我们的结果表明，小檗碱和 GQD 在降低血糖水平、调节肠道微生物群、诱导回肠基因表达以及缓解全身和局部炎症方面具有相似的作用。正如预期的那样，小檗碱和 GQD 治疗都显着改变了整体肠道微生物群结构，并丰富了许多产丁酸盐的细菌，包括粪杆菌和Roseburia，从而减轻肠道炎症并降低葡萄糖。用小檗碱或 GQD 治疗后，大鼠粪便中短链脂肪酸的水平也显着升高。此外，血清促炎细胞因子的浓度和免疫相关基因的表达，包括Nfkb1、Stat1和Ifnrg1在治疗后胰岛中显着降低。我们的研究表明，GQD 的主要作用可归因于小檗碱通过调节肠道微生物群。所采用的策略将促进中医在许多疾病中的进一步标准化和广泛应用。