Exploring the impact of sanguinarine on lamb immunity based on gut microbiota and metabolomics.

INTRODUCTION: Sanguinarine (SNG), a benzophenanthridine alkaloid derived from Macleaya cordata, exerts beneficial effects in monogastric animals; however, its mechanisms of action in ruminants remain poorly understood. This study aimed to explore whether dietary SNG supplementation improves growth performance and immune function in lambs via modulating gut microbiota and host metabolism. METHODS: Lambs received dietary SNG extract at 200 or 800 mg/kg body weight (equivalent to 4 and 16 mg/kg BW pure SNG, respectively). Growth performance, serum immune-antioxidant indices, gut microbiota, and metabolomics profiles were determined to evaluate the treatment effects. RESULTS: SNG supplementation significantly increased average daily gain, up-regulated serum IgG, IL-6 and IFN-γ, and down-regulated IL-4 and IL-10. Antioxidant enzyme activities decreased, whereas malondialdehyde concentration was not altered. Microbiota analysis showed reduced Blautia abundance and increased Monoglobus and Colidextribacter across both SNG-treated groups. Metabolomics revealed modified arachidonic acid (AA) metabolism, with elevated lipid mediators 15(S)-HpEPE and 20-hydroxy LTB4 in SNG-fed lambs. Integrative analysis identified a potential "Blautia-AA-immune" regulatory pattern: high-dose SNG induced a pro-inflammatory Th1-type response, while low-dose SNG sustained immune homeostasis through anti-inflammatory eicosanoids. DISCUSSION: Our findings indicate that SNG improves growth performance and immune function in lambs by reshaping gut microbiota and reprogramming host lipid metabolism. This work provides mechanistic support for the application of SNG as a functional feed additive for ruminants.