Polyphenol-Rich Coffee Leaf Extract Alleviates High-Fat Diet-Induced Intestinal Barrier Dysfunction through Modulation of Barrier Integrity, Enterohepatic Axis, and Gut Microbiota

A polyphenol-rich extract (WEAC) from coffee leaf was previously shown to protect the epithelial barrier integrity. This study investigated the protective effects of WEAC in C57BL/6 mice fed a high-fat diet (HFD). WEAC supplementation (100–200 mg/kg·bw) reduced body weight and lowered TNF-α levels in serum, colon, liver, and brain in mice. WEAC improved mouse intestinal barrier integrity by upregulating the tight-junction protein and reducing intestinal d -lactic acid leakage. Liver histology revealed reduced lipid accumulation and ballooning degeneration, corresponding to decreased triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels. The WEAC intervention also decreased total bile acid levels and altered short-chain fatty acid profiles and key phytochemical metabolism. Furthermore, WEAC reduced the Firmicutes / Bacteroidetes ratio, increased the Parabacteroides, unclassified_Muribaculaceae, and Akkermansia abundance, and lowered the Blautia levels. Additionally, WEAC showed no adverse effects in mice fed a normal diet. Overall, WEAC mitigated HFD-induced intestinal barrier damage and enterohepatic function, reduced systemic inflammation, and stabilized the gut microbiome.