Relationship between neonatal glutamine supplementation and amino acid profiles, protein synthesis in splanchnic tissues and the plasma metabolome in 5-day-old piglets with low birth weight.

The incidence of low birthweight (LBiW) piglets, which show impaired growth compared to normal birthweight (NBiW) littermates, has increased with litter size. We previously reported that glutamine increased the bodyweight and plasma glutamine concentrations in LBiW piglets, with no effect on jejunal glutamine concentrations or glutamine transport and metabolism mRNA abundance. In this study, we investigated the effect of glutamine supplementation on proteinogenic free amino acid (FAA), protein-bound AA (PBAA) and AA-metabolite profiles, mRNA abundance, fractional protein synthesis (FPSR) and the plasma metabolome. At birth (0 days of age (d)), 24 pairs of male LBiW (1.10 kg ± 0.02) and NBiW (1.50 kg ± 0.02) littermates were selected. At 1 d, litters were standardized to 12 piglets, and piglets supplemented daily with either glutamine (1 g/kg bodyweight) or isonitrogenous amounts of alanine (1.22 g/kg bodyweight), until 5 d. Stomach content FAA, AA-metabolites, duodenal and liver tissue FAA, PBAA, AA-metabolites, biochemical indices, duodenal, colon and liver tissue FPSR, liver tissue and duodenal mucosa glutamine transport and metabolism mRNA abundance and the plasma metabolome were analysed. Stomach digesta glutamine (P < 0.001) and glutamate (LBiW, P = 0.02; NBiW, P = 0.03) concentrations were higher in glutamine than alanine piglets. Analysis by Data Integration Analysis for Biomarker Discovery using Latent Variable Approaches for Omics Studies showed glutamine, carnosine, citrulline and alanine separated the supplementation groups, whilst glutathione reductase, glutathione synthetase and tight junction protein 1 mRNA separated glutamine LBiW piglets from alanine. Duodenal RNA was lower and Protein-to-RNA ratio higher (P = 0.004) in glutamine than alanine LBiW piglets (P = 0.02). Colon FPSR was higher in NBiW than LBiW piglets supplemented with Ala. No effects on the plasma metabolome were observed. These results show that not all glutamine passed through the stomach, and that glutamine is absorbed and metabolised in the duodenum, potentially altering the intracellular pH, and appears to increase oxidative stress markers in the duodenum of LBiW piglets.