Antibiotics-induced modulation of large intestinal microbiota altered aromatic amino acid profile and expression of neurotransmitters in the hypothalamus of piglets
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 large intestine harbors greater numbers and more diverse of microbes than in the small intestine, large intestinal microbiota may play a crucial role in the modulation of brain function. In this study, a large intestinal microbiota-targeted strategy was used to investigate the impact of large intestinal microbiota on brain function. 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 or antibiotics. After 25 days of infusion, ileal and fecal microbiota, serum amino acids and neurotransmitters, and hypothalamic transcriptomics were analyzed. While 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-hydroxytryptamine (5-HT) and dopamine, in line with AAAs being their precursors. An up-regulation in gene expressions of neurotransmitter transporters and synthetases was observed (q < 0.001). In conclusion, the distalileal-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 the large intestine, blood and hypothalamus. These findings indirectly indicate that large intestinal microbiota affects hypothalamic neurotransmitter expressions. Read the Editorial Highlight for this article on page 208.
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Antibiotic administration to deplete the GM can change levels of neurotransmitters in the gut and blood.
“antibiotic administration to deplete the GM can change the levels of neurotransmitters in the gut and blood (195, 196).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [195]
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Modulation of Gut Microbial Diversity through Non-Pharmaceutical Approaches to Treat Schizophrenia
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HIV-associated neurocognitive disorder: key implications of the microbiota-gut-brain axis
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Oral antibiotics reduce voluntary exercise behavior in athletic mice
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Effect of TDP43-CTFs35 on Brain Endothelial Cell Functions in Cerebral Ischemic Injury
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Importance of crosstalk between the microbiota and the neuroimmune system for tissue homeostasis
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The microbial guardians: Unveiling the role of gut microbiota in shaping neurodegenerative disease
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Applied physiology: gut microbiota and antimicrobial therapy
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Interaction between Vitamin D homeostasis, gut microbiota, and central precocious puberty
Guo, D., Ning, X., Bai, T., Tan, L., Zhou, Y., Guo, Z. G., & Li, X. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1449033 · Cited by 10 · see citing works
The Interplay between the Gut and Ketogenic Diets in Health and Disease
Mu, C., Rho, J. M., & Shearer, J. (2025) · Advanced Science · doi:10.1002/advs.202504249 · Cited by 11 · see citing works
Self-citationThe Role of Gut Dysbiosis in the Pathophysiology of Tinnitus: A Literature Review
Megantara, I., Wikargana, G. L., Dewi, Y. A., Permana, A. D., & Sylviana, N. (2022) · The International Tinnitus Journal · doi:10.5935/0946-5448.20220005 · Cited by 10 · see citing works
Microbiomes in the Intestine of Developing Pigs: Implications for Nutrition and Health
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Insights into host-microbe interaction: What can we do for the swine industry?
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Omic methodologies for assessing metal(-loid)s-host-microbiota interplay: A review
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LATE-NC Stage 3: a diagnostic rubric to differentiate severe LATE-NC from FTLD-TDP
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Brain, antibiotics, and microbiota – how do they interplay?
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Gut: The gate and key to brain
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When Gut Hormones Influence Brain Function in Depression
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Biosignals in the Gut–Brain Axis Transmission: Function and Detection
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Gut microbiome and gastrointestinal nutrition in animals
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- Authors
- Gao, K., Pi, Y., Mu, C., Peng, Y., Huang, Z., & Zhu, W.
- Affiliations
- Nanjing Agricultural University (CN)
- Laboratory of Gastrointestinal Microbiology Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health National Center for International Research on Animal Gut Nutrition College of Animal Science and Technology Nanjing Agricultural University Nanjing Jiangsu China
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2018-06-28
- Volume
- 146
- Issue
- 3
- Pages
- 219-234
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2789751920
- Cited by
- 119
- References
- 53
- Citations by year
- 2026: 4 · 2025: 18 · 2024: 21 · 2023: 19 · 2022: 20 · 2021: 19 · 2020: 7 · 2019: 9 · 2018: 2
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31430082)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- antibiotic-induced microbiota depletion, aromatic amino acids, hypothalamus, neurotransmitter expression, serotonin, dopamine, gut-brain axis, piglets, neurotransmitter transporters, fecal microbiota
- MeSH terms
- Gastrointestinal Microbiome, Animals, Anti-Bacterial Agents, Chromatography, High Pressure Liquid, Hypothalamus, Intestine, Large, RNA, Messenger, Swine, Neurotransmitter Agents, Amino Acids, Aromatic, Transcriptome, Gene Ontology
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