Injection of amyloid-β to lateral ventricle induces gut microbiota dysbiosis in association with inhibition of cholinergic anti-inflammatory pathways in Alzheimer’s disease
Open accessAbstract
Background: Alzheimer's disease (AD) is the most common neurodegenerative disease and its pathogenesis is still unclear. There is dysbiosis of gut microbiota in AD patients. More importantly, dysbiosis of the gut microbiota has been observed not only in AD patients, but also in patients with mild cognitive impairment (MCI). However, the mechanism of gut microbiota dysbiosis in AD is poorly understood. Cholinergic anti-inflammatory pathway is an important pathway for the central nervous system (CNS) regulation of peripheral immune homeostasis, especially in the gut. Therefore, we speculated that dysfunction of cholinergic anti-inflammatory pathway is a potential pathway for dysbiosis of the gut microbiota in AD. Methods: In this study, we constructed AD model mice by injecting Aβ 1–42 into the lateral ventricle, and detected the cognitive level of mice by the Morris water maze test. In addition, 16S rDNA high-throughput analysis was used to detect the gut microbiota abundance of each group at baseline, 2 weeks and 4 weeks after surgery. Furthermore, immunofluorescence and western blot were used to detect alteration of intestinal structure of mice, cholinergic anti-inflammatory pathway, and APP process of brain and colon in each group. Results: Aβ 1–42 i.c.v induced cognitive impairment and neuron damage in the brain of mice. At the same time, Aβ 1–42 i.c.v induced alteration of gut microbiota at 4 weeks after surgery, while there was no difference at the baseline and 2 weeks after surgery. In addition, changes in colon structure and increased levels of pro-inflammatory factors were detected in Aβ 1–42 treatment group, accompanied by inhibition of cholinergic anti-inflammatory pathways. Amyloidogenic pathways in both the brain and colon were accelerated in Aβ 1–42 treatment group. Conclusions: The present findings suggested that Aβ in the CNS can induce gut microbiota dysbiosis, alter intestinal structure and accelerate the amyloidogenic pathways, which were related to inhibiting cholinergic anti-inflammatory pathways.
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Neuropathological changes in AD brains adversely affect the gut microbiome and intestinal barrier integrity.
“recent evidence has revealed the adverse effects of neuropathological changes in AD brains on the gut microbiome and intestinal barrier integrity.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [634]
Aβ1-42-treated mice began developing alterations in the composition and diversity of gut microbiota 4 weeks post-surgery.
“Aβ1–42-treated mice began developing alterations in the composition and diversity of gut microbiota 4 weeks post-surgery.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [634]
These changes were coupled with elevated intestinal permeability and intestinal inflammation via the inhibition of the cholinergic anti-inflammatory pathway.
“These changes were coupled with elevated intestinal permeability and intestinal inflammation via the inhibition of the cholinergic anti-inflammatory pathway.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [634]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
- Authors
- Qian, X.-H., Liu, X.-L., Chen, G., Chen, S.-D., & Tang, H.-D.
- Affiliations
- Second Affiliated Hospital of Anhui Medical University (CN)
- ORCID
- Chen, Guang
- Venue
- Journal of Neuroinflammation
- Published
- 2022-09-28
- Volume
- 19
- Issue
- 1
- Pages
- 236-236
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC9520842
- OpenAlex
- W4297544419
- Cited by
- 56
- References
- 46
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 19 · 2023: 11
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Shanghai Municipal Health and Family Planning Commission (20184Y0056)
- National Natural Science Foundation of China (82171401, 81971014)
- Shanghai Municipal Science and Technology Major Project (2018SHZDZX05)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta, gut dysbiosis, cholinergic anti-inflammatory pathway, lateral ventricle injection, cognitive impairment, intestinal structure, pro-inflammatory factors, amyloidogenic pathway, APP processing, gut-brain axis, mouse model
- MeSH terms
- Gastrointestinal Microbiome, Alzheimer Disease, Animals, DNA, Ribosomal, Neuroimmunomodulation, Amyloid beta-Peptides, Neurodegenerative Diseases, Lateral Ventricles, Mice, Dysbiosis
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