Protective Effects of Vanillic Acid against IQ-Induced Hepatointestinal Injury: Insights into Ferroptosis and Microbial Changes.

Thermally processed meat products are popular among consumers, but high-temperature processing generates heterocyclic amines (HCAs), particularly the highly toxic 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), which impairs liver and intestinal function. Research has demonstrated that vanillic acid (VA) possesses potent antioxidant and anti-inflammatory activities. However, its protective mechanism against IQ-induced liver injury remains unknown. This study aims to explore VA's mitigation effects and underlying mechanisms. Results reveal that VA alleviates IQ-induced colonic ferroptosis and intestinal barrier damage, modulates the gut microbiota, increases short-chain fatty acids (SCFAs), and inhibits pathogenic bacteria. Furthermore, VA also inhibits activation of the TLR4/MyD88/NF-κB inflammatory cascade by reducing endotoxin transport, thereby preventing assembly and activation of the NLRP3 inflammasome and significantly alleviating liver damage caused by IQ. In conclusion, VA is associated with attenuated IQ-induced liver injury, potentially involving inhibition of ferroptosis, improvement of intestinal barrier integrity, and modulation of the gut microenvironment, supporting microbiota-targeted strategies against hepatotoxicity.