Peanut skin procyanidins ameliorate insulin resistance via modulation of gut microbiota and gut barrier in type 2 diabetic mice

BACKGROUND Peanut skin procyanidins (PSP) have been shown to possess antidiabetic activities. However, the mechanism remains poorly understood due to its low bioavailability. This study aims to investigate the preventive effect of PSP on type 2 diabetes (T2D) in mice through regulating gut microbiota and gut barrier in mice with streptozotocin (STZ)‐induced T2D. During the 30 consecutive days of the study, T2D mice were administered PSP intragastrically at 75, 150 and 300 mg kg−1 body weight d−1. RESULTS PSP treatment obviously alleviated glucolipid metabolism disorders, decreased the levels of lipopolysaccharide (LPS), interleukin (IL)‐6 and myeloperoxidase(MPO), and increased that of IL‐10. PSP treatment enhanced the abundance of Lachnospiraceae_NK4A136_group, Alloprevotella, Akkermansia and Faecalibaculum, and reduced that of Muribaculaceae. Some of these were associated with the production of short‐chain fatty acids and anti‐inflammatory effect, suggesting their important roles in T2D mice. More importantly, PSP improved the gut barrier integrality by restoring gut morphology and enhancing tight junction protein expression including ZO1, claudin1 and occludin in colon. Subsequently, PSP ameliorated insulin resistance by decreasing the LPS/Toll‐like receptor 4/c‐Jun N‐terminal kinase inflammatory response, and enhancing insulin receptor substrate 1/ phosphatidylinositol‐3‐kinase/protein kinase B insulin signaling pathways in the liver. CONCLUSION Peanut skin procyanidins may alleviate the symptoms of T2D by mitigating inflammatory response, modulating gut microbiota and improving intestinal integrity.