Effect of Clostridium butyricum against Microglia‐Mediated Neuroinflammation in Alzheimer's Disease via Regulating Gut Microbiota and Metabolites Butyrate
Abstract
Scope: Recent evidences demonstrate that abnormal gut microbiota (GM) might be involved in the pathogenesis of Alzheimer's disease (AD). However, the role of probiotics in preventing AD by regulating GM–gut–brain axis remains unclear. Here, the anti‐neuroinflammatory effect and its mechanism of probiotic Clostridium butyricum (CB) against AD is investigated by regulating GM–gut–brain axis. Methods and results: APPswe/PS1dE9 (APP/PS1) transgenic are treated intragastrically with CB for 4 weeks then cognitively tested. Amyloid‐β (Aβ) burden, microglial activation, proinflammatory cytokines production, GM, and metabolites butyrate are analyzed. Moreover, Aβ‐induced BV2 microglia are pretreated with butyrate, and the levels of cluster of differentiation 11b (CD11b), cyclooxygenase‐2 (COX‐2), and NF‐κB p65 phosphorylation are determined. The results show that CB treatment prevents cognitive impairment, Aβ deposits, microglia activation, and production of tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β in the brain of APP/PS1 mice. Meanwhile, abnormal GM and butyrate are reversed after CB treatment. Notably, butyrate treatment reduces the levels of CD11b and COX‐2, and suppresses phosphorylation of NF‐κB p65 in the Aβ‐induced BV2 microglia. Conclusions: These findings indicate that CB treatment could attenuate microglia‐mediated neuroinflammation via regulating the GM–gut–brain axis, which is mediated by the metabolite butyrate.
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Probiotic and prebiotic interventions aimed at elevating SCFA levels have neuroprotective effects in AD mouse models by inhibiting glial activation and Aβ deposition.
“Moreover, probiotic and prebiotic interventions aimed at elevating SCFA levels have demonstrated neuroprotective effects in AD mouse models by inhibiting glial activation and Aβ deposition.301–306”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [303]
Elevating butyrate through probiotic intervention with Clostridium butyricum inhibits microglial activation and reduces levels of pro-inflammatory cytokines in APP/PS1 mice.
“Elevating butyrate through probiotic intervention (Clostridium butyricum) has been shown to inhibit microglial activation and reduce the levels of levels pro-inflammatory cytokines in APP/PS1 mice.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [303]
Butyrate exerts anti-inflammatory effects by downregulating COX-2 and CD11b and suppressing NF-κB signaling in Aβ-induced BV-2 cells.
“Furthermore, butyrate exerts anti-inflammatory effects by downregulating the levels of cyclooxygenase-2 (COX-2) and CD11b, and suppressing NF-κB signaling in Aβ-induced BV-2 cells.303”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [303]
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Self-citation
- Authors
- Sun, J., Xu, J., Yang, B., Chen, K., Kong, Y., Fang, N., Gong, T., Wang, F., Ling, Z., & Liu, J.
- Affiliations
- Wenzhou Medical University (CN)
- Department of Surgery The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou 325027 China
- First Affiliated Hospital Zhejiang University (CN)
- Corresponding author
- Ling, Zongxin
- Liu, Jiaming
- Venue
- Molecular Nutrition & Food Research
- Publisher
- Wiley
- Published
- 2019-12-23
- Volume
- 64
- Issue
- 2
- Pages
- e1900636-e1900636
- ISSN
- 1613-4125 (ISSN-L)
- 1613-4133
- OpenAlex
- W2996654920
- Cited by
- 302
- References
- 48
- Citations by year
- 2026: 44 · 2025: 56 · 2024: 64 · 2023: 52 · 2022: 42 · 2021: 28 · 2020: 16
- FWCI
- 9.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Nutrition & Food Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81871094)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- Clostridium butyricum, Alzheimer's disease, neuroinflammation, microglial activation, gut microbiota, butyrate, gut-brain axis, probiotics, APP/PS1 mice, amyloid-beta, inflammatory cytokines, NF-κB p65, cyclooxygenase-2, CD11b, cognitive impairment
- MeSH terms
- Gastrointestinal Microbiome, Alzheimer Disease, Amyloid, Animals, Brain, Butyrates, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, Phosphorylation, Cytokines, Amyloid beta-Peptides, Microglia, Probiotics, Clostridium butyricum, Cyclooxygenase 2, Transcription Factor RelA
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