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The gut microbiome modulates the transformation of microglial subtypes
Open accessAbstract
Clinical and animal studies have shown that gut microbiome disturbances can affect neural function and behaviors via the microbiota–gut–brain axis, and may be implicated in the pathogenesis of several brain diseases. However, exactly how the gut microbiome modulates nervous system activity remains obscure. Here, using a single-cell nucleus sequencing approach, we sought to characterize the cell type–specific transcriptomic changes in the prefrontal cortex and hippocampus derived from germ-free (GF), specific pathogen free, and colonized-GF mice. We found that the absence of gut microbiota resulted in cell-specific transcriptomic changes. Furthermore, microglia transcriptomes were preferentially influenced, which could be effectively reversed by microbial colonization. Significantly, the gut microbiome modulated the mutual transformation of microglial subpopulations in the two regions. Cross-species analysis showed that the transcriptome changes of these microglial subpopulations were mainly associated with Alzheimer’s disease (AD) and major depressive disorder (MDD), which were further supported by animal behavioral tests. Our findings demonstrate that gut microbiota mainly modulate the mutual transformation of microglial subtypes, which may lead to new insights into the pathogenesis of AD and MDD.
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“Notably, among the neuronal and glial cells, microglia are the most vulnerable to alterations in the gut microbiome.189”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [189]
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Metadata
- Authors
- Huang, Y., Wu, J., Zhang, H., Li, Y., Wen, L., Tan, X., Cheng, K., Liu, Y., Pu, J., Liu, L., Wang, H., Li, W., Perry, S. W., Wong, M.-L., Licinio, J., Zheng, P., & Xie, P.
- Affiliations
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Stomatological Hospital of Chongqing Medical University (CN)
- SUNY Upstate Medical University (US)
- Corresponding author
- Zheng, Peng
- Xie, Peng
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2023-03-13
- Volume
- 28
- Issue
- 4
- Pages
- 1611-1621
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC10208978
- OpenAlex
- W4324129695
- Cited by
- 111
- References
- 65
- Citations by year
- 2026: 33 · 2025: 37 · 2024: 31 · 2023: 10
- FWCI
- 11.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- State University of New York
- National Natural Science Foundation of China (82101596, 81820108015, 82171523, 81971296)
- China Postdoctoral Science Foundation (2021MD703928, 2021M693926, 2021TQ0396, 2020TQ0393)
- Chinese Academy of Medical Sciences (2019PT320002)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota, microbiota-gut-brain axis, microglial subtypes, germ-free mice, microbial colonization, prefrontal cortex, hippocampus, cell type-specific transcriptomics, Alzheimer's disease, major depressive disorder, neuroinflammation
- MeSH terms
- Gastrointestinal Microbiome, Alzheimer Disease, Animals, Depression, Major Depressive Disorder, Prefrontal Cortex, Microglia, Mice
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