Comparative multiomics study of the effects of Ellagic acid on the gut environment in young and adult mice

Ellagic acid (EA) is a polyphenol found in fruits and vegetables that can be used as functional ingredient. Accumulating evidence suggests that the effects of EA have large interindividual variability, which is involved in the differences in gut microbiota. However, the mechanisms underlying such effects remain unclear. Here, we found that EA supplementation caused a significant reduction in the body weight of young mice other than adult mice. 16S rRNA gene sequencing revealed that EA significantly affected the abundance of Bacteroides in the young group and Akkermansia and Lactobacillus in the adult group. Short-chain fatty acids (SCFAs) exhibited that the propionic acid and butyric acid levels increased markedly in the young group but not in the adult group. EA activated the expression of peroxisome proliferator-activated receptor gamma (PPARγ), which plays a crucial role in body weight loss. Furthermore, transcriptome analysis showed that the regulated genes mainly correlated with the PPAR signaling pathway related to the endocrine system and lipid metabolism in the young group, whereas the adult group encompassed other various biological processes. The related genes were analyzed by real-time qualitative polymerase chain reaction (RT-qPCR), including the upregulated mRNA expression of Cd36 in the PPAR signaling pathway and Cyp2b9, Cyp7b1, Cyp1a2, Cyp4a32, and Elovl3 associated with lipid metabolism. Spearman's correlation analysis indicated that the bacteria with significant changes in abundance were strongly correlated with the PPAR pathway and lipid metabolism-related genes. This work indicates that the benefits of EA on the gut environment are partly affected by the age of the host and deepens our understanding on how EA regulates the gut environment.