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Accepted Article

DR. KAN

GAO (Orcid ID : 0000-0002-9053-3999)

Article type

: Original Article

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

Running title: Antibiotic infusion altered neurotransmitter expression

Kan Gao1, Yu Pi1, Chun-Long Mu, Yu Peng, Zan Huang, Wei-Yun Zhu* Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P. R. China

1

First Author:

Kan Gao Email Address: [email protected] Yu Pi Email Address: [email protected]

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jnc.14333 This article is protected by copyright. All rights reserved.

Accepted Article

These authors contributed equally to this work.

*Corresponding Author: Professor: Weiyun Zhu Email Address: [email protected]

Abstract: 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