Betulinic acid mitigates lipopolysaccharide-induced intestinal injury of weaned piglets through modulation of the mitochondrial quality control

Intestinal injury of weaned piglets often leads to reduced immunity, diarrhea and growth retardation, resulting in significant economic losses to agriculture. Betulinic acid (BA) is a natural plant-derived active ingredient with multiple pharmacological activities including immune modulation and anti-inflammatory. This study was aimed to investigate the potential mechanism that BA as a feed additive mitigated lipopolysaccharide (LPS)-induced intestinal injury in piglets. The results indicated that BA pretreatment improved the morphology and structure of the intestine, enhanced intestinal mucosal barrier function, and activated the PPAR signaling pathway to reduce the mRNA levels of intestinal CD40 and CXCL13. Meanwhile, BA pretreatment improved the LPS-induced disruption of intestinal microbiota by increasing the abundance of the Firmicutes and decreasing the abundance of the Bacteroidota and Proteobacteria. Furthermore, BA pretreatment activated the AMPK/SIRT1/PGC-1 alpha signaling pathway to enhance mitochondrial biogenesis, restored a balance to mitochondrial dynamics, and modulated the PINK1/Parkin, BNIP3 and FUNDC1 signaling pathways to activate mitophagy, thereby alleviating LPS-induced intestinal injury. Overall, the present study elucidated that dietary supplementation with BA could alleviate LPS-induced intestinal injury in weaned piglets by regulating mitochondrial quality control, which provided a novel approach for alleviating intestinal stress in weaned piglets.