Tannic acid breaks hepatic persistence of Salmonella and promotes Kupffer cell M2 polarization via the gut-liver axis in broilers

ABSTRACT Salmonella is a significant foodborne threat to the poultry industry, particularly affecting chicks. Tannic acid (TA), a polyphenol found in plants like chestnut and plum trees, offers antioxidant and anti-inflammatory benefits. This study examined the protective effects of TA on growth performance, gut microbiota, gut barrier function, and liver immune damage in broilers infected with Salmonella . Results indicated that Salmonella infection significantly reduced chick growth ( P < 0.05) and compromised intestinal health, leading to chronic inflammation. Although Salmonella was undetectable in the intestines and feces 10 days post-infection, it translocated to the liver, causing subclinical infections. This resulted in M1 polarization of hepatic Kupffer cells and increased inflammatory factors ( P < 0.05), disrupting liver immune homeostasis. Dietary supplementation with 200 mg/kg TA could effectively improve their growth performance, protect the intestinal barrier, promote intestinal health, inhibit the colonization of Salmonella in the liver, repair the immune microenvironmental homeostasis in the liver, and improve the hepatic immune function of the broilers. This study suggests that TA protects the intestines and liver from Salmonella damage by reducing inflammation, repairing the intestinal barrier, decreasing Salmonella colonization in the liver, improving the liver’s immune environment, and modulating metabolic disorders. This study elucidates the mechanism by which Salmonella induces persistent liver colonization and hepatic immune dysregulation through the gut-liver axis. Furthermore, it highlights TA’s potential as an antibiotic alternative to reduce Salmonella -induced liver immune damage through the gut-liver axis, offering a new approach to poultry health management. IMPORTANCE This research addresses a critical challenge in poultry production: controlling persistent Salmonella infections that evade conventional treatments and contribute to foodborne illness. We show how Salmonella can “hide” in the liver after disappearing from the gut, causing ongoing health problems for the birds. More importantly, our findings reveal that a natural plant compound, tannic acid, can effectively break this cycle. Instead of directly killing the bacteria, it works by strengthening the gut and recalibrating the liver’s immune defenses. This offers a novel, host-directed strategy to combat bacterial infections. Our work provides a scientific foundation for using tannic acid as a sustainable antibiotic alternative in animal feed, which could lead to healthier poultry and safer food products, with significant implications for both animal agriculture and public health.