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Intestinal microbiota elicits IL‐17A production in neutrophil by regulating RORγt signaling and accelerated the pace of inflammageing in cerebral small vessel disease
Author(s) -
Hu Mengyan,
Cai Wei,
Lu Zhengqi
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.046987
Subject(s) - immune system , disease , immunology , biology , gut flora , microbiome , medicine , bioinformatics , pathology
Background Intestinal microbiota shapes the host immune system and influences the outcomes of various neurological disorders. Cerebral small vessels disease (CSVD) is highly prevalent among the elderly with its pathological mechanisms yet incompletely understood. The current study investigates the microbiota ecology in CSVD patients, particularly its impact on host’s immune system. Method Fresh fecal samples (∼500mg) were donated by recruited CSVD patients (n=55) or healthy controls (n=62) for high‐throughput 16S ribosomal RNA gene amplicon sequencing. Laboratory tests and standard magnetic resonance imaging (MRI) were performed in above 2 groups for cardiovascular risk factors screening and neuroimaging assessment respectively. The central immune organ of spleen from healthy wild type C57/Bl6 mouse and primary neutrophil cultures were used to explore the mechanisms of CSVD. Result Altered composition of gut microflora was associated with undesirable disease outcomes and exacerbated inflammageing status. Neutrophils were activated by CSVD associated microflora and obtain increased capacity of IL‐17A production when were exposed to the fecal bacterial extracts from CSVD patients. Mechanistically, RORγt signaling in neutrophils was activated by CSVD associated gut bacterial extracts to upregulate IL‐17A production. Conclusion Our findings revealed a previously unrecognized implication of gut‐immune‐brain axis in CSVD pathophysiology, with therapeutic implications.