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

## TL;DR

Adding Lactobacillus reuteri to piglet diets improves growth and gut-liver metabolism by boosting amino acid transport and reducing intestinal collagen buildup.

## Contribution

The study identifies Lactobacillus reuteri LR1 as a probiotic that modulates amino acid metabolism and extracellular matrix in the gut–liver axis of weaned piglets.

## Key findings

- LR1 improved growth performance, ileum villus height, and amino acid transporter expression in piglets.
- LR1 elevated serum glycine, hydroxyproline, and hepatic taurine levels, with 11 amino-acid-related metabolites upregulated in portal plasma.
- LR1 reduced ileum collagen deposition and was linked to metabolic reprogramming in the gut–liver axis.

## Abstract

This study demonstrates that dietary supplementation with Lactobacillus reuteri LR1 alleviates weaning stress in piglets by enhancing growth and gut–liver axis metabolism. In a 21-day trial with 48 weaned piglets, LR1 significantly improved growth performance, and LR1 enhanced intestinal nutrient absorption via increased ileum villus height and upregulated amino acid transporters. Metabolically, LR1 elevated serum glycine, hydroxyproline, and hepatic taurine levels, with untargeted metabolomics identifying 11 amino-acid-related metabolites upregulated in portal plasma. Histological analysis revealed reduced ileum collagen deposition, and correlation analysis linked collagen dynamics to gut–liver axis amino acid metabolic reprogramming. This study highlights LR1 as a promising probiotic for optimizing nutrient utilization and promoting intestinal development in piglets, and the intestinal extracellular matrix may be a key target for improving amino acid transport 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 Lactobacillus reuteri LR1 on growth performance and amino acid metabolism in the gut–liver axis of weaned piglets. A total of 48 weaned piglets (Duroc × Landrace × Yorkshire, 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 Lactobacillus reuteri 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 (p < 0.05). Additionally, LR1 significantly enhanced the villus height of the ileum (p < 0.05) and upregulated the expression of SLC6A19 in the jejunum, as well as SLC6A19, SLC7A1, and SLC38A9 in the ileum (p < 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.