Distal ileal antibiotic infusion affects the expressions of neurotransmitters in the hypothalamus of piglets

Purpose: Gut microbiota-brain axis serves as an emerging pathway affecting brain function. Hindgut has a higher proportion of microbes than foregut, however whether alteration in hindgut microbiota is related to brain functional change remains unclear. The present study used antibiotics to modulate the hindgut microbiota, to investigate the changes in the functions of porcine hypothalamus. Methods: Twelve piglets (12.08 ± 0.28 kg) fitted with T-cannula at the distal ileum were fed a standard diet and randomly assigned to two groups (n=6) for ileal infusions of saline (control group) and an antibiotic mix (ampicillin, gentamycin and metronidazole; antibiotic group), respectively. After the 25-day experiment, the microbiota and metabolites in feces, concentrations of amino acids and neurotransmitters in hypothalamus and blood, and transcriptomics profiles of hypothalamus were analyzed. Results: The results showed that the antibiotic infusion resulted in an increase in aromatic amino acids (AAA)-utilizing genera, notably Lactobacillus, and a decrease in the concentrations of AAAs including tryptophan, tyrosine and phenylalanine in feces. Correspondingly, concentrations of AAAs in the blood and hypothalamus also decreased. In the hypothalamus, the concentrations of AAAs related neurotransmitters 5-HT and dopamine decreased. Meanwhile, the compensatory upregulations of neurotransmitter transporter genes such as SERT, DAT and synthesis-related genes TPH2 and AADC were observed (adjusted P < 0.001). Furthermore, the concentrations of 5-HT and dopamine decreased in the blood. Conclusion: In conclusion, the results revealed that the ileal antibiotic infusion could affect the expressions of neurotransmitters in the porcine hypothalamus. The changes of hindgut microbial composition, circulating AAA profile and hypothalamic neurotransmitter expressions indirectly suggested that the hindgut microbiota may affect the brain functions. Overall design: Hypothalamic mRNA profiles of pigs in control and ileal antibiotic infusion groups were generated by deep sequencing, control group with 4 replicates, antibiotic group with 3 replicates, using Illumina HiSeq 2000.

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Gao K, Pi Y, Mu CL, Peng Y, Huang Z, Zhu WY