Zinc methionine mitigates intestinal mucosal injury of broilers challenged with Salmonella by modulating mucus secretion, tight junction and microbial composition.

The investigation aimed to reveal potential mechanisms of zinc methionine on the intestinal mucosal function of Salmonella-challenged broilers. Totally, 320 Ross 308 male chicks were divided into 4 treatments, with 8 repetition per group and 10 chicks each. A 2 × 2 factor in a randomized block design was employed to explore the impacts of zinc addition, Salmonella challenge, and their interactions. The experiment lasted for 21 days. Results indicated that Salmonella infection decreased (P < 0.05) average daily gain (ADG) and the ratio of villus height to crypt depth (V/C) in both jejunum and ileum. The infection also reduced (P < 0.05) MUC2 and KLF4 mRNA levels, while elevating (P < 0.05) feed to gain (F:G), caudal-related homeobox transcriptional regulator 2 (CDX2) mRNA level, and altering (P < 0.05) bacterial composition. In contrast, zinc addition increased (P < 0.05) ADG, average daily feed intake, jejunal villus height, V/C, and tight junction mRNA expressions, but decreased (P < 0.05) F:G and CDX2 mRNA level. Moreover, zinc enhanced (P < 0.05) jejunal goblet cell number and ileal mucus thickness, and restored (P < 0.05) bacterial abundance. Correlation analysis found that zinc-enriched bacterial genera, including g_Butyricicoccus, g_Oscillibacter and g_Monoglobus were significantly positively correlated with broilers' growth performance and intestinal morphology and tight junction Claudin-1 mRNA. CUT&Tag-seq analysis further demonstrated KLF4 binds to the exon region of MUC2 gene, but CDX2 did not bind to MUC2 promoter region. These suggest zinc mitigates Salmonella induced intestinal mucosal damage by promoting mucus secretion and tight junction mRNA expression, and microbial community reshaping, but not by improving KLF4-mediated MUC2 gene expression.