The differences in hypoglycemic activity of Coptis herb pairs fermented by Eurotium cristatum and its regulatory effect on gut microbiota in T2DM rats

Coptidis Rhizoma-Scutellariae Radix, Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma, and Coptidis Rhizoma-Panax notoginseng are herbal pairs widely used in clinical therapy for Type 2 Diabetes Mellitus (T2DM) and gastrointestinal diseases. The fungus Eurotium cristatum , known for its robust enzyme system and diverse active metabolites, possesses a strong potential for the biotransformation of active constituents in Coptis-containing herbal pairs. However, the hypoglycemic effects and underlying mechanisms of these fermented pairs remain unclear. This study systematically evaluated the effects of three E. cristatum -fermented Coptis herbal pairs on fasting blood glucose (FBG), glucose tolerance, lipid metabolism (TC, TG, HDL-C and LDL-C), pancreatic injury protection, and gut microbiota composition in T2DM rats. The fermented Coptis-Glycyrrhiza (FRG) and Coptis-Scutellaria (FRS) demonstrated pronounced effects in improving physical condition, attenuating weight loss, and achieving stable glycemic control. Three fermented pairs regulated total cholesterol (TC) more effectively than metformin, and FRS exhibited superior protection against pancreatic islet injury. Different fermented Coptidis herb-pairs exert distinct effects on gut microbiota composition in T2DM rats. The FRS significantly enriched beneficial genera, including unclassified_f_ Oscillospiraceae , norank_o_ Clostridia _UCG-014, Monoglobus and Ruminococcus . The FRP significantly increased the abundance of beneficial genera such as Lachnospiraceae _NK4A136_group, Monoglobus , Ruminococcus , norank_o_ Clostridia _UCG-014 and Acutalibacter , etc. The FRG was characterized by higher abundances of Ligilactobacillus , norank_f_ Lachnospiraceae , Akkermansia , and Prevotellaceae _UCG-001. These findings suggest that the differential hypoglycemic effects of three fermented Coptis pairs are closely linked to regulation of gut microbiota dysbiosis. Our data highlight the potential of optimizing Coptis-based formulations for T2DM treatment and open new avenues for traditional Chinese medicine.