Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Department of Nutrition, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Food Res Int. 2024 Sep;192:114852. doi: 10.1016/j.foodres.2024.114852. Epub 2024 Jul 27.
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.
克罗恩病（CD）是一种慢性、进行性炎症性疾病，可累及胃肠道的任何部位。在 CD 的临床前模型中已经证实了膳食多酚的保护作用。肠道微生物群介导多酚的代谢，并影响其生物活性和生理功能。然而，CD 患者和健康对照者（HCs）的微生物多酚代谢能力及其与多酚摄入和多酚衍生代谢物的相关性仍然难以捉摸。因此，我们旨在通过饮食、肠道微生物群和代谢物方面来解码 CD 患者的多酚代谢。饮食摄入分析表明，CD 患者的多酚摄入量减少。使用来自两个独立临床队列（FAH-SYSU 和 PRISM）的宏基因组数据，我们量化了 CD 和 HCs 中与多酚降解相关的细菌和功能基因的丰度，并观察到 CD 患者肠道微生物群中黄酮类化合物降解能力较低。此外，通过对 FAH-SYSU 队列参与者的血清代谢物和肠型进行分析，我们观察到 CD 患者的血清马尿酸（HA）水平降低，HA 是一种多酚衍生的代谢物。在更健康的肠型（以 Ruminococcaceae 和 Prevotellaceae 为主导，主要为 HCs ）中，HA 水平较高，与多种多酚摄入以及参与黄酮类化合物降解和短链脂肪酸产生的细菌丰度呈正相关，这可以作为肠道微生物群有效多酚代谢和更健康肠道微生物群落结构的生物标志物。总的来说，我们的研究结果为探索基于多酚或靶向微生物群的 CD 治疗策略提供了基础。
