Cited by 80Gut microbiota and healthAcute Ischemic Stroke ManagementNeuroinflammation and Neurodegeneration Mechanisms

Indole-3-propionic acid alleviates ischemic brain injury in a mouse middle cerebral artery occlusion model

Xie, Yu, Zou, Xiaoxiong, Han, Jianbang, Zhang, Zhongfei, Feng, Zhiming, Ouyang, Qian, Hua, Shiting, Liu, Zhizheng +5 more·2022·Experimental Neurology

Abstract

Increasing evidence highlights the importance of gut microbiota and its metabolites as an environmental factor affecting ischemic stroke. However, the role of microbial indole metabolites in ischemic stroke remains largely unknown. Here, we evaluated the effects and the underlying mechanism of indole-3-propionic acid (IPA) in a mouse model of acute middle cerebral artery occlusion (MCAO) and the mechanisms underlying these effects. We collected blood samples and evaluated serum indole derivatives levels using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS) in 8-10-week-old male C57 mice undergoing MCAO or sham. Intragastric IPA administration (400 μg/20 g/d) was performed in mice with MCAO, and its effects and mechanisms were assessed. We found that the serum IPA levels were significantly lower in mice with MCAO than in sham-treated subjects. 16S rRNA gene sequencing revealed that IPA treatment ameliorated the MCAO-induced alterations of the gut microbiome structure, specifically reshaping the microbial community composition in mice with MCAO to resemble that in the mice from the control group, with an increase in the abundance of probiotics and a decrease in the abundance of harmful bacteria. IPA repaired the integrity of the intestinal barrier and regulated the activities of regulatory T cells (Tregs) and Th17 cells in the gut-associated lymphoid tissue. Intragastric IPA administration effectively alleviated neuroinflammation, neurological impairment and brain infarction. Of note, Tregs in the IPA treatment group inhibited A1 reactive astrogliosis in vitro. The beneficial effects of IPA are thus mediated by the gut microbiota, which could enable the development of prebiotics for microbiome-based treatments for ischemic stroke.

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Crossref · 10.1016/j.expneurol.2022.114081

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Authors
Xie, Y., Zou, X., Han, J., Zhang, Z., Feng, Z., Ouyang, Q., Hua, S., Liu, Z., Li, C., Cai, Y., Zou, Y., Tang, Y., & Jiang, X.
Affiliations
Zhujiang Hospital (CN)
Corresponding author
Jiang, Xiaodan
Venue
Experimental Neurology
Publisher
Elsevier BV
Published
2022-07
Volume
353
Pages
114081
ISSN
0014-4886 (ISSN-L)
OpenAlex
W4223595127
Cited by
80
References
56
Citations by year
2026: 17 · 2025: 26 · 2024: 20 · 2023: 14 · 2022: 3
FWCI
5.12
Type
journal article
Language
en
Open access
closed
Locations
  • Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Foundation for Innovative Research Groups of the National Natural Science Foundation of China
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
indole-3-propionic acid, ischemic stroke, middle cerebral artery occlusion, gut microbiota, microbial metabolites, gut-brain axis, intestinal barrier, regulatory T cells, Th17 cells, neuroinflammation, reactive astrogliosis, prebiotics, probiotics
MeSH terms
Ischemic Stroke, Animals, Brain Injuries, Chromatography, Liquid, Disease Models, Animal, Humans, Indoles, Male, Propionates, RNA, Ribosomal, 16S, Infarction, Middle Cerebral Artery, Mice, Tandem Mass Spectrometry

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