The microbiota-gut-brain axis participates in chronic cerebral hypoperfusion by disrupting the metabolism of short-chain fatty acids
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Background: Chronic cerebral hypoperfusion (CCH) underlies secondary brain injury following certain metabolic disorders and central nervous system (CNS) diseases. Dysregulation of the microbiota-gut-brain axis can exacerbate various CNS disorders through aberrantly expressed metabolites such as short-chain fatty acids (SCFAs). Yet, its relationship with CCH remains to be demonstrated. And if so, it is of interest to explore whether restoring gut microbiota to maintain SCFA metabolism could protect against CCH. Results: Rats subjected to bilateral common carotid artery occlusion (BCCAO) as a model of CCH exhibited cognitive impairment, depressive-like behaviors, decreased gut motility, and compromised gut barrier functions. The 16S ribosomal RNA gene sequencing revealed an abnormal gut microbiota profile and decreased relative abundance of some representative SCFA producers, with the decreased hippocampal SCFAs as the further evidence. Using fecal microbiota transplantation (FMT), rats recolonized with a balanced gut microbiome acquired a higher level of hippocampal SCFAs, as well as decreased neuroinflammation when exposed to lipopolysaccharide. Healthy FMT promoted gut motility and gut barrier functions, and improved cognitive decline and depressive-like behaviors by inhibiting hippocampal neuronal apoptosis in BCCAO rats. Long-term SCFA supplementation further confirmed its neuroprotective effect in terms of relieving inflammatory response and hippocampal neuronal apoptosis following BCCAO. Conclusion: Our results demonstrate that modulating the gut microbiome via FMT can ameliorate BCCAO-induced gut dysbiosis, cognitive decline, and depressive-like behaviors, possibly by enhancing the relative abundance of SCFA-producing floras and subsequently increasing SCFA levels.
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Modulation of the gut microbiota and supplementation with SCFAs promoted gastrointestinal transit, modulated intestinal barrier function in a rat model of bilateral carotid artery obstruction, and improved symptoms of cognitive decline and depressive-like behavior.
“Xiao et al. (59) found that modulation of the gut microbiota and supplementation with SCFAs promoted gastrointestinal transit, and modulated intestinal barrier function in a rat model of bilateral carotid artery obstruction, as well as improving symptoms of cognitive decline and depressive-like behavior, revealing the neuroprotective potential of gastrointestinal microbes.”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [59]
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- Authors
- Xiao, W., Su, J., Gao, X., Yang, H., Weng, R., Ni, W., & Gu, Y.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Fudan University (CN)
- Corresponding author
- Ni, Wei
- Gu, Yuxiang
- Venue
- Microbiome
- Published
- 2022-04-17
- Volume
- 10
- Issue
- 1
- Pages
- 62-62
- ISSN
- 2049-2618 (ISSN-L)
- PMC
- PMC9013454
- OpenAlex
- W4224080430
- Cited by
- 252
- References
- 86
- Citations by year
- 2026: 47 · 2025: 91 · 2024: 73 · 2023: 37 · 2022: 4
- FWCI
- 16.72
- Type
- journal article
- Language
- en
- Update notices
- Open access
- gold
- doi.org
- Locations
- Microbiome (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Innovative Research Group Project of the National Natural Science Foundation of China (82171313, 81870917, 81771237, 82101397)
- Ministry of Human Resources and Social Security (2016YFC1301704)
- Science and Technology Commission of Shanghai Municipality (2018SHZDZX01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- microbiota-gut-brain axis, chronic cerebral hypoperfusion, short-chain fatty acids, gut dysbiosis, fecal microbiota transplantation, bilateral common carotid artery occlusion, cognitive impairment, depression-like behavior, neuroinflammation, hippocampal neuronal apoptosis, intestinal motility, intestinal barrier, neuroprotection
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Brain-Gut Axis, Animals, Fatty Acids, Volatile, Mice, Inbred C57BL, Mice, Rats
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