In vitro fermentation characteristics of licochalcone A and its regulatory effects on human gut microbiota via multi-omics analysis.

Historically, bioactive flavonoids from plant foods have been important components of the human diet and play key roles in shaping gut microbiota composition and host metabolism. Licochalcone A (LCA), a chalcone-type flavonoid derived from licorice (Glycyrrhiza spp.), has gained attention for its potential interactions with gut microbial communities. In the present study, an in vitro fecal batch fermentation system using samples from six healthy volunteers was used to characterize LCA-induced changes in microbial composition and metabolism. LCA was rapidly metabolized by the intestinal microbiota within 48 h, with pronounced interindividual variability among donors, indicating active microbial transformation. LCA treatment altered microbial activity by modifying short-chain fatty acid profiles, including acetate, propionate, and butyrate. LCA significantly increased the relative abundance of beneficial bacteria, including Prevotella, Segatella, and Bacteroides, while decreasing the abundance of taxa such as Fusobacterium and Escherichia. Untargeted metabolomics of the fermented broth revealed that LCA reshaped the gut metabolome, enriching metabolites involved in tryptophan metabolism and pantothenate and coenzyme A biosynthesis. Several metabolites, including Romucosine, Mosin C, and lucidone B, were altered, suggesting changes in microbial metabolic activity. Overall, these findings demonstrate that LCA can reshape gut microbial composition and metabolism, providing a basis for future development of functional foods.