Octanoic Acid‐Rich Enteral Nutrition Regulates Intestinal M1 / M2 Macrophage Polarization via the PPARγ / STAT ‐1/ STAT ‐6 Pathway to Alleviate Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a complex chronic intestinal inflammatory disease involving immune, genetic and environmental interactions. A disrupted balance in the polarization of intestinal macrophages is a key pathogenic link. This study explored whether octanoic acid (OA)‐rich enteral nutrition (EN) regulated intestinal M1/M2 macrophage polarization via the PPARγ/STAT‐1/STAT‐6 pathway to alleviate IBD. First, to assess the effects of OA‐rich EN on IBD, four groups were established: the sham, IBD, IBD + EN, and IBD + OA‐rich EN. Second, to verify the regulatory role of intestinal M1/M2 macrophage polarization via the PPARγ/STAT‐1/STAT‐6 pathway, six groups were established: the sham, IBD, IBD + OA‐rich EN, IBD + OA‐rich EN with intraperitoneal injections of IFNγ, AS1517499, or SR202. RAW264.7 cells were also used to observe how OA influences LPS/IFNγ‐induced M1 polarization. OA‐rich EN notably alleviated IBD symptoms, activated the PPARγ/STAT‐1/STAT‐6 pathway and remodeled the M1/M2 polarization balance of intestinal macrophages. These effects were greater than those in the IBD + EN group. Blocking the activation of PPARγ, activating STAT‐1 or inhibiting STAT‐6 reversed the protective effect of OA‐rich EN on remodeling the M1/M2 polarization balance of intestinal macrophages and IBD symptoms. In vitro experiments further confirmed that OA regulated macrophage polarization via the PPARγ/STAT‐1/STAT‐6 pathway. This is the first confirmation that OA‐rich EN alleviates IBD by activating PPARγ/STAT‐1/STAT‐6 to regulate macrophage polarization, highlighting its potential as a nutritional therapy for IBD.