Indole-3-aldehyde\nAlleviates High-Fat Diet-Induced\nGut Barrier Disruption by Increasing Intestinal Stem Cell Expansion

High-fat diet (HFD) feeding is known to cause intestinal\nbarrier\ndisruption, thereby triggering severe intestinal inflammatory disease.\nIndole-3-aldehyde (IAld) has emerged as a potential candidate for\nmitigating inflammatory responses and maintaining intestinal homeostasis.\nHowever, the role of IAld in the HFD-related intestinal disruption\nremains unclear. In this study, 48 7 week-old male C57BL/6J mice were\nassigned to four groups: the normal chow diet (NCD) group received\na NCD; the HFD group was fed an HFD; the HFD + IAld200 group was supplemented\nwith 200 mg/kg IAld in the HFD; and the HFD + IAld600 group was supplemented\nwith 600 mg/kg IAld in the HFD. The results showed that dietary IAld\nsupplementation ameliorated fat accumulation and metabolic disorders,\nwhich are associated with reduced intestinal permeability. This reduction\npotentially led to decreased systemic inflammation and enhanced intestinal\nbarrier function in HFD-fed mice. Furthermore, we found that IAld\npromoted intestinal stem cell (ISC) proliferation by activating aryl\nhydrocarbon receptors (AHRs) in vivo and ex vivo. These findings suggest\nthat IAld restores the HFD-induced intestinal barrier disruption by\npromoting AHR-mediated ISC proliferation.