Fermented grape pomace alleviates Salmonella typhimurium-induced Hepatointestinal inflammation: FXR mediates protection by orchestrating bile acid homeostasis and suppressing the colonic NLRP3 Inflammasome

Grape pomace, a winemaking by-product rich in Polyphenols, has limited bioavailability due to the co-existence of anti-nutritional factors. This study was conducted to investigate whether solid-state fermented grape pomace (FGP) could alleviate Salmonella typhimurium-induced inflammation and explored the underlying mechanisms. The results showed that solid-state fermentation reduced the content of insoluble dietary fiber and macromolecular tannins, while increasing the in vitro antioxidant activity, soluble dietary fiber, crude protein, and acid-soluble protein content of grape pomace. Mice were fed diets supplemented with 0%, 1%, 2%, or 4% FGP and were challenged with or without S. typhimurium (1 × 10⁷ CFU). Results showed that 2% FGP supplementation effectively mitigated S. typhimurium-induced body weight loss, colon shortening, liver damage, and oxidative stress. FGP intervention activated the farnesoid X receptor (FXR) in the liver and ileum, thereby restoring bile acid homeostasis. In colon, FGP suppressed the nuclear factor kappa B (NF-κB) pathway and NOD-like Receptor family pyrin domain containing 3 (NLRP3) inflammasome activation, thereby reducing inflammation and improving barrier integrity. Furthermore, FGP reshaped the gut microbiota by enriching beneficial genera such as Adlercreutzia and Limosilactobacillus, and promoted the production of secondary bile acids, which contributed to FXR activation and NLRP3 inhibition. Notably, these protective effects were largely abolished by an FXR inhibitor. In conclusion, FGP alleviates systemic inflammatory damage by modulating the gut microbiota-bile acid-FXR axis and suppressing the colonic NLRP3 pathway, providing a novel dietary intervention strategy using fermented plant by-products against enteric infections.