The dynamics impact of phlorizin on gut microbiota and metabolites in an in vitro fermentation model

The multiple beneficial effects, but low bioavailability of phlorizin (PHZ) have sparked discussion about its role in interaction with the gut microbiota. In this study, the effects of PHZ on the fecal microbiota animals of different origins were investigated using an in vitro fermentation model. In the fermentation system of PHZ using SD rat feces, the dynamic variations of the bacterial profile, SCFAs, and organic acids were detected using 16S rRNA gene sequencing, GC-MS, and LC-MS/MS. The results showed that PHZ treatment significantly increased the phylum Bacteroidota and transiently reduced Firmicutes at 6 h. At the genus level, PHZ consistently increased the abundance of Lactobacillus (especially Lactobacillus johnsonii), significantly decreased the abundance of Ligilactobacillus and Limosilactobacillus, and temporarily suppressed Streptococcus after 12 h. Similarly, in the fermentation system using db/db mouse feces, PHZ enriched the abundance of Lactobacillus and Lactobacillus johnsonii. Monoculture of Lactobacillus johnsonii ATCC 33200 showed that PHZ could directly stimulate its growth. Meanwhile, we found that PHZ could significantly increase the production of butyric, isobutyric, isovaleric, valeric, and caproic acids. Organic acid analysis showed an increasing trend in succinic acid and a significant reduction in L-malic acid in the post-PHZ group. Correlation analysis revealed that the abundance of Lactobacillus positively correlated with the concentration of SCFAs and succinic acid, while negatively correlated with L-malic acid. These findings suggest that PHZ may regulate intestinal balance by promoting Lactobacillus johnsonii growth and modulating SCFA and specific organic acid levels. Our study highlights that natural polyphenol PHZ has a health-promoting potential by modulating gut microbiota.