Curcumin ameliorates Salmonella-induced enteritis by restraining NF-κB signaling and restoring microbiota-SCFA homeostasis.

Foodborne Salmonella infection triggers excessive inflammation, mucosal injury and gut microbiota dysbiosis. Here, curcumin was evaluated as a dietary bioactive against Salmonella-induced enteritis using in silico target-network analysis, macrophage assays and a mouse infection model. Target-network analysis identified 79 shared targets associated with curcumin and intestinal inflammation. In vitro, macrophages were treated with curcumin at 40 and 80 μM before stimulation with lipopolysaccharide or Salmonella Enteritidis infection. In vivo, mice were challenged with S. Enteritidis and orally gavaged with curcumin at 100 or 200 mg per kg body weight. Curcumin inhibited LPS- and Salmonella-induced NF-κB activation in J774-Dual/RAW264.7 macrophages, decreased IL-1β, IL-6 and TNF-α, increased IL-10, and reduced lactate dehydrogenase release by over 35%. In infected mice, curcumin alleviated clinical deterioration (weight loss and hemolysis), attenuated liver and spleen injury, lowered tissue bacterial burden by nearly 2log10 CFU per 100 mg, and improved intestinal histopathology. Notably, 16S rDNA profiling showed that curcumin reversed Salmonella-driven dysbiosis by improving microbial diversity, limiting Proteobacteria/Enterobacteriaceae expansion, and enriching beneficial taxa including Lactobacillus. These compositional shifts were accompanied by recovery of key short-chain fatty acids by 40%-75% (acetate, propionate, butyrate and valerate), indicating restoration of microbiota-linked metabolic homeostasis. Collectively, curcumin mitigates pathogen-associated intestinal inflammation while rebuilding the microbiota-SCFA homeostasis supportive of mucosal barrier function, supporting its development as a food-derived functional ingredient.