Antibiotics-induced modulation of large intestinal microbiota altered aromatic amino acid profile and expression of neurotransmitters in the hypothalamus of piglets

The evidence of gut microbiota-mediated modulation of brain function has been widely recognized from studies using germ-free rodents or animals with oral antibiotic-induced microbiota depletion. Since the number of bacteria in the large intestine greatly exceeds that found within the small intestine, large intestinal microbiota may play a crucial role in the modulation of brain function. In the present study, twelve piglets (12.08 ± 0.28 kg) fitted with a T-cannula at the distal ileum were fed a standard diet and randomly assigned to two groups (n=6) for ileal infusion of either saline (control group) or antibiotics (antibiotic group). After 25-days of infusion, ileal and fecal microbiota, serum amino acids and neurotransmitters, and hypothalamic transcriptomics were analyzed. Whilst the antibiotic infusion did not change the proximal ileal microbial composition, it markedly altered the fecal microbial composition and increased aromatic amino acid (AAAs) metabolism (P <0.05), suggesting the infusion specifically targeted large intestinal microbes. Concentrations of AAAs were likewise decreased in the blood and hypothalamus (P <0.05) by antibiotic infusion. Antibiotic infusion further decreased concentrations of hypothalamic 5-HT and dopamine, in line with AAAs being their precursors. Furthermore, an upregulation in gene expressions of neurotransmitter transporters and synthetases was observed (q <0.001). In conclusion, the ileal-antibiotic infusion altered neurotransmitter expression in the porcine hypothalamus and this effect occurred simultaneously with changes in both the large intestinal microbiota, and AAAs in large intestine, blood and hypothalamus. These findings indirectly indicate that large intestinal microbiota affects hypothalamic neurotransmitter expressions. This article is protected by copyright. All rights reserved.