Neuroprotective Effects of Clostridium butyricum against Vascular Dementia in Mice via Metabolic Butyrate
Open accessAbstract
Probiotics actively participate in neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and vascular dementia (VaD) remains unclear. We used a mouse model of VaD induced by a permanent right unilateral common carotid arteries occlusion (rUCCAO) to investigate the neuroprotective effects and possible underlying mechanisms of Clostridium butyricum. Following rUCCAO, C. butyricum was intragastrically administered for 6 successive weeks. Cognitive function was estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The BDNF-PI3K/Akt pathway-related proteins were assessed by western blot and immunohistochemistry. The diversity of gut microbiota and the levels of butyrate in the feces and the brains were determined. The results showed that C. butyricum significantly attenuated the cognitive dysfunction and histopathological changes in VaD mice. C. butyricum not only increased the levels of BDNF and Bcl-2 and decreased level of Bax but also induced Akt phosphorylation (p-Akt) and ultimately reduced neuronal apoptosis. Moreover, C. butyricum could regulate the gut microbiota and restore the butyrate content in the feces and the brains. These results suggest that C. butyricum might be effective in the treatment of VaD by regulating the gut-brain axis and that it can be considered a new therapeutic strategy against VaD.
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Levels of butyrate in the brain of mice supplemented with live Clostridium butyricum reached 0.4 to 0.7 μmol/g, about an order of magnitude higher than concentrations reported in peripheral blood.
“the levels of butyrate in the brain of mice supplemented with live Clostridium butyricum reached a range from 0.4 to 0.7 μmol/g, which was about an order of magnitude higher than concentrations reported in peripheral blood (96, 97).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [96]
Results §3.6 reports that higher-dose live C. butyricum treatment increased brain butyrate in mice with vascular dementia. Our copy does not state the claimed 0.4–0.7 μmol/g range or compare brain levels with peripheral-blood concentrations; it refers to Figure 8 for the measurements. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSix weeks of administration with the probiotic Clostridium butyricum restored cognitive function in a mouse model for vascular dementia, which was associated with increased butyrate levels in fecal and brain samples and activation of the hippocampal BDNF-PI3K/Akt pathway.
“Six weeks of administration with the probiotic Clostridium butyricum restored cognitive function in a mouse model for vascular dementia, which was associated with increased butyrate levels in fecal and brain samples, and activation of the hippocampal BDNF-PI3K/Akt pathway (392).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [392]
Administration of the SCFA butyrate improves cognitive impairments in a mouse model of vascular dementia.
“In a study by Liu et al., administration of the SCFA butyrate improved cognitive impairments in a mouse model of vascular dementia (392).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [392]
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- Authors
- Liu, J., Sun, J., Wang, F., Yu, X., Ling, Z., Li, H., Zhang, H., Jin, J., Chen, W., Pang, M., Yu, J., He, Y., & Xu, J.
- Affiliations
- Wenzhou Medical University (CN)
- School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
- First Affiliated Hospital Zhejiang University (CN)
- Xi'an Jiaotong University (CN)
- Corresponding author
- Xu, Jiru
- ORCID
- Venue
- BioMed Research International
- Publisher
- Wiley
- Published
- 2015
- Volume
- 2015
- Pages
- 1-12
- ISSN
- 1110-7243 (ISSN-L)
- 2314-6133
- 2314-6141
- PMC
- PMC4615854
- OpenAlex
- W2114102190
- Cited by
- 225
- References
- 46
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 26 · 2023: 33 · 2022: 32 · 2021: 24 · 2020: 25 · 2019: 21 · 2018: 14 · 2017: 5 · 2016: 7 · 2015: 1
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- BioMed Research International (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Zhejiang Science and Technology Development Funds (2015C37090, LY13B070012)
- Natural Science Foundation of Zhejiang Province (2015C37090, LY13B070012)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- Clostridium butyricum, vascular dementia, butyrate, gut microbiota, gut-brain axis, neuroprotection, cognitive impairment, neuronal apoptosis, brain-derived neurotrophic factor, PI3K/Akt signaling, carotid artery occlusion, probiotics
- MeSH terms
- Animals, Brain, Butyrates, Carotid Arteries, Disease Models, Animal, Hippocampus, Immunohistochemistry, Male, Mice, Inbred ICR, Microscopy, Electron, Phosphorylation, Dementia, Vascular, Apoptosis, Neuroprotective Agents, Brain-Derived Neurotrophic Factor, Phosphatidylinositol 3-Kinases, Probiotics, Clostridium butyricum, Mice
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