Hesperidin ameliorates 2,4,6-Trinitrobenzenesulfonic Acid (TNBS)-induced colitis in mice via regulating tryptophan metabolism, AhR signaling pathway, and gut microbiota

Crohn's disease (CD) is a chronic inflammatory bowel disease with limited treatment options. Hesperidin (HES), a citrus flavonoid, exhibits anti-inflammatory and antioxidant properties, yet its therapeutic potential in CD remains poorly understood. Here, we demonstrate that HES administration ameliorates TNBS-induced colitis in mice by restoring immune homeostasis, enhancing epithelial barrier integrity, and reshaping gut microbiota composition. Specifically, HES promotes the growth of beneficial bacteria such as Alistipes, facilitates microbial indole metabolism, and increases production of indole-3-propionic acid (IPA). Both in vivo and in vitro analyses confirm that HES activates the aryl hydrocarbon receptor (AhR) pathway, which plays a pivotal role in maintaining intestinal homeostasis. Our findings reveal that HES alleviates experimental colitis through coordinated regulation of the gut microbiota-indole metabolism-AhR axis, highlighting its potential as a therapeutic agent for CD.

克罗恩病（Crohn's disease, CD）是一种治疗选择有限的慢性炎症性肠病。橙皮苷（Hesperidin, HES）作为一种柑橘类黄酮，具有抗炎与抗氧化特性，但其在CD中的治疗潜力仍未得到充分阐明。本研究证实，通过恢复免疫稳态、增强上皮屏障完整性以及重塑肠道菌群组成，橙皮苷给药可改善小鼠体内三硝基苯磺酸（TNBS）诱导的结肠炎。具体而言，橙皮苷可促进阿里斯梯氏菌属（Alistipes）等有益菌的生长，促进微生物吲哚代谢，并提升吲哚-3-丙酸（indole-3-propionic acid, IPA）的生成量。体内与体外实验分析均证实，橙皮苷可激活芳香烃受体（aryl hydrocarbon receptor, AhR）通路，该通路在维持肠道稳态中发挥关键作用。本研究结果显示，橙皮苷通过协同调控肠道菌群-吲哚代谢-芳香烃受体轴缓解实验性结肠炎，凸显其作为CD治疗药物的潜在价值。