State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo City 315211, China.
School of Marine Science, Ningbo University, Ningbo City 315832, China.
J Agric Food Chem. 2023 May 24;71(20):7710-7722. doi: 10.1021/acs.jafc.3c00830. Epub 2023 May 11.
Urolithin A (UroA) is a microbial metabolite derived from ellagitannins and ellagic acid with good bioavailability. In this study, we explored the anticolitis activity of UroA and clarified the mechanism by 16S rDNA sequencing and metabonomics. UroA alleviated dextran sulfate sodium (DSS)-induced colitis in mice, characterized by a decreased disease activity index, increased colon length, and improved colonic histopathological lesions, along with inhibited phosphorylation of the mitogen-activated protein kinase signaling pathway. In addition, UroA improved gut microbiota dysbiosis and modulated the microbiota metabolome. Furthermore, targeted metabolomics focused on tryptophan catabolites showed that UroA significantly increased the production of indole-3-aldehyde (IAld) and subsequently led to increased colonic expression of aryl hydrocarbon receptor (AhR) and promoted the serum content of IL-22 in mice with colitis. Collectively, our data identified a novel anticolitis mechanism of UroA by improving gut microbiota dysbiosis, modulating microbial tryptophan metabolism, promoting IAld production, and triggering AhR/IL-22 axis activation. However, a limitation noted in this study is that these beneficial effects of UroA were found at 50 μM and 20 mg/kg , which were nonphysiological concentrations.
尿石素 A（UroA）是一种微生物代谢产物，来源于鞣花单宁和鞣花酸，具有良好的生物利用度。在这项研究中，我们通过 16S rDNA 测序和代谢组学探索了 UroA 的抗结肠炎活性，并阐明了其作用机制。UroA 缓解了葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎，表现为疾病活动指数降低、结肠长度增加和结肠组织病理学损伤改善，同时抑制了丝裂原活化蛋白激酶信号通路的磷酸化。此外，UroA 改善了肠道微生物失调并调节了微生物代谢组。此外，靶向代谢组学集中于色氨酸代谢物表明，UroA 显著增加了吲哚-3-醛（IAld）的产生，随后导致结肠炎小鼠结肠中芳香烃受体（AhR）的表达增加，并促进了血清中 IL-22 的含量。总之，我们的数据通过改善肠道微生物失调、调节微生物色氨酸代谢、促进 IAld 产生以及触发 AhR/IL-22 轴激活，确定了 UroA 的一种新型抗结肠炎作用机制。然而，本研究中注意到一个局限性，即 UroA 的这些有益作用是在 50 μM 和 20 mg/kg 时发现的，这是非生理浓度。
