Preventive effects of polysaccharides from Physalis alkekengi L. on dietary advanced glycation end product-induced insulin resistance in mice associated with the modulation of gut microbiota

Advanced glycation end products (AGEs) are commonly found in thermally processed foods, and long-term high AGE feeding has been reported to have negative effects on body health. In the current study, the effect of Physalis alkekengi L. fruit polysaccharide (PFP) on preventing dietary AGE-induced insulin resistance (IR) in mice was investigated. The results showed that PFP administration can significantly ameliorate hyperglycemia, dyslipidemia, and insulin resistance induced by dietary AGEs in mice. Compared to AGE-treated mice, the homeostasis model assessment for insulin resistance (HOMA-IR) index and insulin sensitivity (HOMA-IS) index of PFP-treated mice were improved significantly (p < 0.05). The levels of endotoxin and inflammatory cytokines in the liver decreased, while the levels of insulin receptor substrate-1 and insulin receptor substrate-2 in the liver increased (p < 0.05). The 16S rRNA analysis showed that PFP administration reversed the Bacteroidetes/Firmicutes ratio and reduced lipopolysaccharide generation and inflammation-related bacteria, including Desulfovibrio and Acetatifactor. In addition, PFP administration also increased short-chain fatty acid levels in feces compared to dietary AGE-treated mice. Spearman's correlation analysis showed that certain specific genera, including Alistipes and Caproiciproducens, are closely related to IR-related parameters. These findings suggest that PFP can prevent dietary AGE-induced IR by modulating the gut microbiota and increasing microbial metabolites.