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

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.