Metabolites of esterified derivative 3,5-Dicaffeoylquinic acid dodecyl ester fermented by Lactobacillus plantarum in the gut mediate bile acid metabolism and alleviate obesity via FXR/SHP/LRH-1 pathway in high-fat diet induced obese mice

The 3,5-dicaffeoylquinic acid (3,5-DiCQA), a key component of Chuzhou chrysanthemum, one of the “Four Major Edible Chrysanthemums” in China, has been shown to enrich beneficial gut bacteria and reduce lipid synthesis based on its hydroxycinnamic acid structures. However, its low lipophilicity limits bioactivity, necessitating the development of more stable derivatives. Therefore, this study synthesized and characterized a novel esterified derivative 3,5-DiCQA dodecyl ester (3,5-DiCQAD) with markedly enhanced lipophilicity and bioactivity. In high-fat diet (HFD)-induced male C57BL/6J mice, 3,5-DiCQAD showed remarkable metabolic regulatory effects, including improvements in glucose metabolism, lipid homeostasis, BA signaling, and thermogenesis. Furthermore, 3,5-DiCQAD effectively reshaped the gut microbiota, enriching beneficial bacteria such as Lactobacillus plantarum . Moreover, the strain L. plantarum ZZ 240321 was isolated, and its fermentation of 3,5-DiCQAD generated metabolites that modulated bile acid (BA) metabolism through the FXR/SHP/LRH-1 pathway, alleviating obesity-related symptoms in antibiotic-treated mice. This research provides a novel perspective for developing plant-derived polyphenols as anti-obesity treatments. It also broadens the understanding of DiCQA's probiotic potential in the gut microbiome, highlighting its promising role in managing metabolism-associated disorders.