Oleanolic Acid Regulates Intestinal Cell Proliferation and Protein Synthesis Capacity in Piglets via the Bile Acid-TGR5/AMPK/mTOR Axis

Takeda G protein-coupled receptor 5 (TGR5) plays a critical role in bile acid-mediated regulation of gut health, yet its underlying mechanisms are only partially defined. Our study demonstrates that supplementing piglet feed with 50 mg/kg oleanolic acid (OA) for 20 days significantly reduces serum and intestinal total bile acid concentrations, suppresses TGR5 expression, increases the apparent digestibility of crude protein and amino acids, and promotes intestinal cell proliferation. Using TGR5/pCREB-Luc cells, we observed that hyocholic acid (HCA) activates the TGR5/AMPK pathway while concurrently inhibiting activation of the mTOR pathway, resulting in suppressed cell proliferation and protein synthesis. Notably, targeted inhibition of the TGR5/AMPK pathway reverses these effects. These results strongly support the potential application of oleanolic acid as a functional food or feed additive to improve gut health and offer new perspectives on nutritional interventions targeting the "bile acid-TGR5" axis in the context of intestinal disorders.