Mulberry Polyphenols Ameliorate Metabolic Abnormalities Accompanied by Spatial Microbial and Short-Chain Fatty Acid Alterations in Type 2 Diabetic Mice

The gut microbiota may contribute to the anti-diabetic effects of mulberry polyphenols (MPs), although the associated spatial microbial patterns and metabolic alterations remain unclear. We investigated microbiota composition in fecal, cecal, and colonic samples and temporal changes in fecal short-chain fatty acids (SCFAs) during an 8-week MP intervention in type 2 diabetic (T2DM) mice using 16S rRNA sequencing and gas chromatography. MPs effectively reduced fasting blood glucose and improved diabetes-associated pathological alterations. Spatially, MP administration was associated with distinct changes in the ascending colonic microecology, characterized by an increased relative abundance of Allobaculum in the lumen and a 23.17% reduction in the relative abundance of mucosa-associated Helicobacter. At the phylum level, MPs increased fecal Bacteroidetes by 7.16% and reduced the relative abundance of Actinobacteria in the cecal, transverse, and descending colonic contents (decreased by 17.03%, 27.24%, and 15.08%, respectively). Temporally, MP administration was associated with time-dependent changes in fecal SCFA concentrations, especially acetate, butyrate, and isobutyrate. Collectively, MP administration was associated with improved glycemic control and coordinated spatial microbial alterations and temporal SCFA changes, characterized by pronounced microbial compositional changes in the ascending-colon region and time-dependent increases in SCFA concentrations over time. These findings provide insights into polyphenol-associated microbiota alterations and support further investigation of the microbial and metabolic responses to MPs in T2DM.