Polyphenols extracted from Lycium barbarum seeds regulate gut microbiota to improve type 2 diabetes mellitus in db/db mice.

BACKGROUND

Mounting evidence positions the gut microbiota as a pivotal player in the onset and progression of type 2 diabetes mellitus (T2DM). Lycium barbarum seed polyphenols (LBSPs), a byproduct of Lycium barbarum processing, have shown antioxidant and anti-inflammatory bioactivities, but potential anti-T2DM effects remain unclear.

PURPOSE: To evaluate the preventive effects of LBSPs against T2DM and the associated gut microbiota mechanisms.

METHODS

The effects of LBSPs on fasting blood glucose, insulin sensitivity, liver lipid accumulation, intestinal barrier, gut microbiota composition, and microbial metabolites were investigated in db/db mice.

RESULTS

LBSPs significantly reduced fasting blood glucose, improved insulin sensitivity, and alleviated dyslipidemia and hepatic steatosis in db/db mice. Furthermore, LBSPs restored intestinal barrier integrity by up-regulating tight junction proteins Claudin-1, Occludin, and Zonula Occludens-1 (ZO-1). 16S rRNA analysis revealed that LBSPs reversed gut microbiota dysbiosis, enriching Lactobacillus, Ligilactobacillus, Rikenella, Lachnospiraceae_NK4A136_group, while decreasing Escherichia-Shigella and Klebsiella. Mechanically, LBSPs can modulate aromatic amino acid metabolism, lipid metabolism, and bile acid biosynthesis by metabolomics. Mediation analysis indicated that specific gut microbiota influenced host metabolic parameters through metabolites such as 7-megastigmene-3,6,9-triol 9-glucoside.

CONCLUSION

Our findings reveal that LBSPs can be used as a potential microbiota-targeted nutraceutical that reverses gut microbiota dysbiosis and diabetes-associated metabolic disorders during T2DM progression.