Antibiotic-induced microbiome depletion in adult mice disrupts blood-brain barrier and facilitates brain infiltration of monocytes after bone-marrow transplantation
Abstract
The crosstalk between intestinal bacteria and the central nervous system, so called "the gut-brain axis", is critically important for maintaining brain homeostasis and function. This study aimed to investigate the integrity of the blood-brain barrier (BBB) and migration of bone marrow (BM)-derived cells to the brain parenchyma after intestinal microbiota depletion in adult mice. Gut microbiota dysbiosis was induced with 5 non-absorbable antibiotics in drinking water in mice that had received bone marrow transplantation (BMT) from green fluorescent protein (GFP) transgenic mice. Antibiotic-induced microbiome depletion reduced expression of tight-junction proteins of the brain blood vessels and increased BBB permeability. Fecal microbiota transplantation of antibiotics treated mice with pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. The BM-derived GFP+ cells were observed to infiltrate specific brain regions, including the nucleus accumbens (NAc), the septal nucleus (SPT) and the hippocampus (CA3). The infiltrated cells acquired a ramified microglia-like morphology and Iba1, a microglia marker, was expressed in all GFP+ cells, whereas they were negative for the astrocyte marker GFAP. Furthermore, treatment with CCR2 antagonist (RS102895) suppressed the recruitment of BM-derived monocytes to the brain. We report for the first time the migration of BM-derived monocytes to the brain regions involved in regulating emotional behaviors after depletion of intestinal microbiota in BMT background mice. However, mechanisms responsible for the migration and functions of the microglia-like infiltrated cells in the brain need further investigation. These findings indicate that monocyte recruitment to the brain in response to gut microbiota dysbiosis may represent a novel cellular mechanism that contributes to the development of brain disorders.
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Antibiotic-treated mice displayed greater BBB permeability and reduced TJ proteins, which were partially ameliorated following FMT from SPF mice.
“Antibiotic-treated mice displayed greater BBB permeability and reduced TJ proteins, which were partially ameliorated following FMT from SPF mice.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [665]
Gut microbiota-derived metabolites are important regulators of BBB integrity.
“Ample evidence has shown that gut microbiota-derived metabolites are important regulators of BBB integrity”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [665]
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- Authors
- Sun, N., Hu, H., Wang, F., Li, L., Zhu, W., Shen, Y., Xiu, J., & Xu, Q.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Xiu, Jianbo
- Xu, Qi
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 92
- Pages
- 102-114
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W3106702912
- Cited by
- 75
- References
- 53
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 12 · 2023: 9 · 2022: 8 · 2021: 9
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Research and Development Program of China
- Beijing Municipal Science and Technology Commission
- National Natural Science Foundation of China
- Fundamental Research Funds for the Central Universities
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- gut-brain axis, antibiotic-induced dysbiosis, blood-brain barrier permeability, tight junction proteins, bone marrow-derived monocytes, microglia-like cells, CCR2 antagonist, brain infiltration, emotional behavior, brain disorders
- MeSH terms
- Animals, Anti-Bacterial Agents, Blood-Brain Barrier, Bone Marrow, Brain, Mice, Inbred C57BL, Mice, Transgenic, Monocytes, Bone Marrow Transplantation, Mice, Microbiota
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