Abstract: This study aimed to reveal the critical role of the interaction between procyanidins and the gut microbiota in regulating obesity. Changes in the body mass, body fat, and homeostatic model assessment of insulin resistance index (HOMA-IR) of high-fat diet-induced obese mice were analyzed after administration with different doses of peanut skin procyanidins (PSP), and gut microbiota diversity and fecal metabolomics were examined by 16S rRNA gene sequencing and high performance liquid chromatography-mass spectrometry (HPLC-MS). The results showed that PSP alleviated obesity, insulin resistance, and liver ectopic fat accumulation in high-fat diet mice. PSP decreased the ratio of Firmicutes to Bacteroidetes, significantly up-regulating the abundance of Akkermansia, Bacteroides, Alistipes, and Parabacteroides, and down-regulating the abundance of Blautia. PSP inhibited the accumulation of oxidative lipids such as 9-hydroxyoctadecadienoic acid (9-HODE), 9,10-dihydroxy-12Z,15Z-octadecadienoic acid (9,10-DHOME), 9,10-dihydroxy-12Z-octadecenoic acid (9,10-DiHODE), and 9,10,13-trihydroxy-11-octadecenoic acid (9,10,13-TriHOME) in the feces of obese mice, and up-regulated the levels of bile acids including muricholic acid, 12-ketolithocholic acid, and deoxycholic acid. Moreover, the proanthocyanidins A1 and A2 in PSP, as well as PSP-derived metabolites including 4-hydroxy-5-phenylvaleric acid, 5-(3’,4’-dihydroxy)-γ-valerolactone, and dehydroxylated C-ring opened catechin, were positively correlated with gut microbial genera such as Alistipes, Parabacteroides, and Akkermansia, which in turn influenced the levels of fecal metabolites, including urobilinogen, stearic acid, lysophosphatidylcholine (16:0), 9,10-DiHODE, and 9,10-DHOME. The interaction between PSP-derived microbial metabolites and endogenous metabolites altered gut microbiota balance, ultimately affecting the body mass and insulin resistance of mice.

Key words: procyanidins; gut microbiota; metabolites; obesity