Indole-3-propionic acid alleviates DSS-induced colitis in mice through macrophage glycolipid metabolism.

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease for which current therapeutic approaches still face many dilemmas, and targeting macrophage polarization and metabolism for the treatment of this disease is a potentially effective strategy. The gut microbial metabolite indole-3-propionic acid (IPA) has favorable anti-inflammatory and antioxidant effects and plays a role in a variety of disease models. IPA is effective in the treatment of UC, but the underlying mechanisms have not been well explored. In the present study, we investigated the mechanisms by which IPA ameliorates colitis in mice from the perspective of macrophage polarization and metabolism. In this study, mice colitis was induced by sodium dextran sulfate and treated with oral IPA. RAW264.7 cells were induced by LPS to polarize into M1 macrophages and treated with IPA. The results showed that IPA could improve colitis by inhibiting M1 polarization of colonic macrophages and promoting M2 polarization. The inhibition of IPA on M1 macrophages was verified in vitro through JNK/MAPK pathway, which inhibited the glycolysis of macrophages. IPA promotes macrophage M2 polarization and enhances fatty acid oxidation through upregulating of CPT1A and ACSL1, which may be related to the activation of PPAR-γ. In summary, IPA can improve colitis by regulating macrophage glucose and lipid metabolism, and targeting intestinal macrophage metabolism may be an effective target for the treatment of UC.