Porous starch microspheres loaded with luteolin exhibit hypoglycemic activities and alter gut microbial communities in type 2 diabetes mellitus mice

Luteolin (LUT), a natural flavonoid known for its hypoglycemic properties, is primarily sourced from vegetables such as celery and broccoli. However, its poor stability and low bioavailability in the upper digestive tract hinder its application in the functional food industry. To address these challenges, this study employed porous starch (PS) as a carrier to develop PS microspheres loaded with luteolin (PSLUT), simulating its release <i>in vitro</i>. The research assessed the hypoglycemic effects of LUT in type 2 diabetes mellitus (T2DM) mice both before and after PS treatment. <i>In vitro</i> findings demonstrated that PS improved LUT's stability in simulated gastric fluids and enhanced its <i>in vivo</i> bioavailability, aligning with experimental outcomes. PSLUT administration significantly improved body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), pancreatic islet function, and other relevant indicators in T2DM mice. Moreover, PSLUT alleviated abnormal liver biochemical indicators and liver tissue injury caused by T2DM. The underlying hypoglycemic mechanism of PSLUT is thought to involve the regulation of protein kinase B (AKT-1) and glucose transporter 2 (GLUT-2). After four weeks of intervention, various PSLUT doses significantly reduced the <i>Firmicutes</i> to <i>Bacteroidetes</i> ratio at the phylum level and decreased the relative abundance of harmful bacteria at the genus level, including <i>Acetatifactor</i>, <i>Candidatus-Arthromitus</i>, and <i>Turicibacter</i>. This microbial shift was associated with improvements in hyperglycemia-related indicators such as FBG, the area under the curve (AUC) of OGTT, and homeostasis model assessment of insulin resistance (HOMA-IR), which are closely linked to these bacterial genera. Additionally, <i>Lachnoclostridium</i>, <i>Parasutterella</i>, <i>Turicibacter</i>, and <i>Papillibacter</i> were identified as key intestinal marker genera involved in T2DM progression through Spearman correlation analysis. In conclusion, PS enhanced LUT's hypoglycemic efficacy by modulating the transcription and protein expression levels of AKT-1 and GLUT-2, as well as the relative abundance of potential gut pathogens in T2DM mice. These results provide a theoretical foundation for advancing luteolin's application in the functional food industry and further investigating its hypoglycemic potential.