Dietary Supplementation of Lactobacillus reuteri Modulates Amino Acid Metabolism and Extracellular Matrix in the Gut–Liver Axis of Weaned Piglets

Weaning stress leads to intestinal dysfunction and impaired growth performance and intestinal development in piglets. This study aims to investigate the effects of <i>Lactobacillus reuteri</i> LR1 on growth performance and amino acid metabolism in the gut-liver axis of weaned piglets. A total of 48 weaned piglets (<i>Duroc × Landrace × Yorkshire</i>, 21 days old) were randomly assigned to the CON group (fed a basal diet) and the LR1 group (fed the basal diet supplemented with 5 × 10¹⁰ CFU/kg of <i>Lactobacillus reuteri</i> LR1) with six pens per group and 4 piglets each pen. The results demonstrated that LR1 significantly increased average daily gain (ADG), average daily feed intake (ADFI), and final body weight (<i>p</i> < 0.05). Additionally, LR1 significantly enhanced the villus height of the ileum (<i>p</i> < 0.05) and upregulated the expression of SLC6A19 in the jejunum, as well as SLC6A19, SLC7A1, and SLC38A9 in the ileum (<i>p</i> < 0.05). Amino acid analysis revealed that LR1 elevated the serum concentrations of glycine and hydroxyproline, along with increased taurine in the liver. Masson staining indicated LR1 reduced ileum fiber deposition, with COL3A1 identified as a key component. Furthermore, untargeted metabolomic analysis identified 27 amino acid-related differential metabolites and 11 significantly up-regulated in the plasma of the hepatic portal vein, including L-asparagine, L-citrulline, His-Cys, N-acetyltryptophan, 4-hydroxy-l-isoleucine, Gly-Arg, creatine, ornithine, ectoine, 3-methyl-l-histidine, and stachydrine. Correlation analysis suggested that COL1A2 and COL3A1 were closely associated with these metabolic changes. Overall, these findings suggest that LR1 supplementation promotes growth, improves intestinal morphology, reduces fiber deposition, and enhances amino acid metabolism in the gut-liver axis of weaned piglets.