Decoding polyphenol metabolism in patients with Crohn's disease: Insights from diet, gut microbiota, and metabolites

Crohn's disease (CD) is a chronic and progressive inflammatory disease that can involve any part of the gastrointestinal tract. The protective role of dietary polyphenols has been documented in preclinical models of CD. Gut microbiota mediates the metabolism of polyphenols and affects their bioactivity and physiological functions. However, it remains elusive the capacity of microbial polyphenol metabolism in CD patients and healthy controls (HCs) along with its correlation with polyphenols intake and polyphenol-derived metabolites. Thus, we aimed to decode polyphenol metabolism in CD patients through aspects of diet, gut microbiota, and metabolites. Dietary intake analysis revealed that CD patients exhibited decreased intake of polyphenols. Using metagenomic data from two independent clinical cohorts (FAH-SYSU and PRISM), we quantified abundance of polyphenol degradation associated bacteria and functional genes in CD and HCs and observed a lower capacity of flavonoids degradation in gut microbiota residing in CD patients. Furthermore, through analysis of serum metabolites and enterotypes in participants of FAH-SYSU cohort, we observed that CD patients exhibited reduced levels of serum hippuric acid (HA), one of polyphenol-derived metabolites. HA level was higher in healthier enterotypes (characterized by dominance of Ruminococcaceae and Prevotellaceae, dominant by HCs) and positively correlated with multiple polyphenols intake and abundance of bacteria engaged in flavonoids degradation as well as short-chain fatty acid production, which could serve as a biomarker for effective polyphenol metabolism by the gut microbiota and a healthier gut microbial community structure. Overall, our findings provide a foundation for future work exploring the polyphenol-based or microbiota-targeted therapeutic strategies in CD.