Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt
Author(s) -
Wei Cai,
Xiaodong Chen,
Xuejiao Men,
Hengfang Ruan,
Mengyan Hu,
Sanxin Liu,
Tingting Lü,
Jinchi Liao,
Bingjun Zhang,
Danli Lu,
Yig Huang,
Ping Fan,
Junping Rao,
Chunyan Lei,
Jihui Wang,
Xiaomeng Ma,
Qiang Zhu,
Lili Li,
XiuYun Zhu,
Hou Yujiao,
Shu Li,
Qing Dong,
Qing Tian,
Lulu Ai,
Wenjing Luo,
Mengyun Zuo,
Liping Shen,
Congyan Xie,
Hongzhong Song,
Ganlin Xu,
Kangdi Zheng,
Zhao Zhang,
Yongjun Lu,
Wei Qiu,
Tao Chen,
Andy Peng Xiang,
Zhengqi Lu
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abe4827
Subject(s) - dysbiosis , gut flora , immunology , biology , medicine
The intestinal microbiota shape the host immune system and influence the outcomes of various neurological disorders. Arteriosclerotic cerebral small vessel disease (aCSVD) is highly prevalent among the elderly with its pathological mechanisms yet is incompletely understood. The current study investigated the ecology of gut microbiota in patients with aCSVD, particularly its impact on the host immune system. We reported that the altered composition of gut microbiota was associated with undesirable disease outcomes and exacerbated inflammaging status. When exposed to the fecal bacterial extracts from a patient with aCSVD, human and mouse neutrophils were activated, and capacity of interleukin-17A (IL-17A) production was increased. Mechanistically, RORγt signaling in neutrophils was activated by aCSVD-associated gut bacterial extracts to up-regulate IL-17A production. Our findings revealed a previously unrecognized implication of the gut-immune-brain axis in aCSVD pathophysiology, with therapeutic implications.
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