BackgroundThis study aimed to evaluate the effect of N‐carbamylglutamate (NCG) on the piglets’ growth performance and immune response, and unravel their mechanisms. In a 2 × 2 factorial design including diet (with or without NCG) and immunological challenge (saline or lipopolysaccharide (LPS)), 24 piglets were randomly distributed to four groups. After being fed a basic diet or a NCG‐supplemented diet for 21 days, piglets were administered LPS or saline intraperitoneally.ResultsThe results showed that NCG increased average daily gain and average daily feed intake, and feed conversion ratio of piglets, and alleviated the adverse effects of LPS stimulation about intestinal morphology. At the phylum level, NCG reversed the changes of the increase in Firmicutes and decrease in Actinomycete abundance caused by LPS stimulation. At the genus level, NCG increased the abundances of Lactobacillus, Blautia, norank_Butyricicoccaceae, Subdoligranulum, and Ruminococcus_gauvreauii_group, while LPS decreased the abundances of Escherichia‐Shigella and Ruminococcus_gauvreauii_group. The content of short‐chain fatty acids was raised by NCG, while LPS reduced its content. Additionally, NCG significantly inhibited the LPS‐induced increase in the relative expression of signal transducer and activator of transcription (STAT) 3, RAR related orphan receptor c, and pro‐inflammatory cytokines, and the decrease in the relative expression of STAT5, forkhead box P3, IL‐10 and transforming growth factor‐beta 1 mRNAs. A significant correlation was found between intestinal microbiota and inflammatory cytokines and short‐chain fatty acids.ConclusionCollectively, NCG can improve piglets’ growth performance. NCG can also attenuate LPS‐induced intestinal inflammation by modulating microbiota and Th17/Treg balance‐related immune signaling pathways.This article is protected by copyright. All rights reserved.