This paper combined histopathology, blood biochemistry, and high-throughput analytical techniques (microbial diversity and metabolomics of liver and flora) to study the mitigating effect and mechanism of different concentrations (0.16, 0.12, 0.08, 0.04 mg/mL) of pheophorbide a (Pheo a) on the liver and intestinal damage induced by high-fat diet.Body weight results showed that the body weight of mice in the high-concentration group (0.16, 0.12 mg/mL) was significantly lower than that of the high-fat dietary control group (P<0.05).Blood glucose values were measured and found to be in the normal range in the high-concentration group, while the low-concentration group (0.08, 0.04 mg/mL) and the high-fat dietary control group were in the range of pre-diabetic blood glucose values.The results of serum indexes showed that pheophorbide a significantly reduced the high-fat diet-induced triglyceride, insulin, IL-6, IL-1β, and malondialdehyde expression levels (P<0.05) in a dose-dependent manner.Liver metabolomics results showed significant changes in metabolites of nicotinoylglycine, succinic acid, alanine, glutamic acid, and valine (P<0.05).Microbial diversity results revealed that the experimental group significantly increased the abundance of Muribaculaceae and Lactobacillus and decreased the abundance of Clostridium at the genus level (P<0.05).Metabolomics of intestinal flora revealed significant changed in metabolites such as oxalacetic acid, methyl-2-hydroxyisobutyric acid, and α-ketoglutaric acid (P<0.05).In conclusion, pheophorbide a could effectively delay weight gain and have a regulatory effect on the intestinal flora of mice, significantly reversing high-fat diet-induced intestinal flora dysbiosis and reducing high-fat diet-induced low-grade inflammation, which in turn alleviates the metabolic syndrome and promotes the health of the organism, and the corresponding regulatory mechanisms need to be studied in depth.
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