P1227 Revealing lower capacity of microbial metabolism of flavonoids and associated metabolic changes in Crohn’s disease

Abstract

Abstract Background Recent studies highlight the role of interplay between oxidative stress, gut microbiota, and immune response in the etiology of Crohn’s disease (CD). Polyphenols are natural antioxidants which are mainly metabolized by gut microbiota and could modulate the composition of gut microbiota. However, it’s yet reported whether there is difference in polyphenol-degradation capacity of gut microbiota in CD and healthy controls (HCs). Methods A comprehensive literature search was conducted on microbial metabolic pathway of polyphenols and the responsible organisms and genes were recorded. The polyphenol-degrading genes were quantified using shortBRED in three clinical cohorts (the First Affiliated Hospital of Sun Yat-sen University (FAH) cohort, PRISM cohort, and HMP2 cohort). Microbiota abundance was analyzed in FAH and PRISM cohort. Polyphenol intake and serum metabolites were assessed in the FAH cohort. Enterotype analysis was performed in FAH cohort. Correlation analysis among polyphenol intake, gene abundance, serum metabolites and bacterial abundance was conducted. Results Phylogenetic tree revealed that reported polyphenol-degrading bacteria were mainly distributed to Actinobacteria and Firmicutes. The abundance of flavonoid degradation related genes (mainly flavone reductase, chalcone isomerase and phloretin hydrolase) was significantly decreased in patients with CD in FAH cohort, but not in PRISM and HMP cohort. Difference in abundance of polyphenol-degrading bacteria was observed between CD patients and HCs in FAH and PRISM cohort. In addition, lower polyphenols intake and serum hippuric acid (HA) level were detected in CD patients. Enterotype analysis revealed that CD patients were mainly distributed to Enterobacteriaceae- and Bacteroidaceae-dominated enterotype while HCs were mainly distributed to Ruminococcaceae- and Prevotellaceae-dominated enterotype. Serum HA level was higher in healthier enterotypes (Ruminococcaceae and Prevotellaceae dominant) and positively correlated with flavonoid-degrading organisms and butyric acid-producing organisms. No positive correlation between abundance of polyphenol-degradation genes and polyphenols intake was detected. Conclusion The current study summarized the polyphenol metabolic pathway mediated by gut microbiota and quantified genes responsible for polyphenol degradation. Our comprehensive analysis of diet-microbiota-gene-metabolite data revealed a lower capability of flavonoid degradation in gut microbiota and lower HA level in CD patients. Finally, our findings provide a foundation for future work exploring the polyphenol or polyphenol-degrading microbiota interventions in preclinical models of CD.