2. Academic Validation
  3. Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt

Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt

  • Sci Adv. 2021 Jan 22;7(4):eabe4827. doi: 10.1126/sciadv.abe4827.
Wei Cai 1 2 3,  Xiaodong Chen 1,  Xuejiao Men 1,  Hengfang Ruan 1,  Mengyan Hu 1,  Sanxin Liu 1,  Tingting Lu 1,  Jinchi Liao 1,  Bingjun Zhang 1,  Danli Lu 1,  Yinong Huang 1,  Ping Fan 1,  Junping Rao 4,  Chunyan Lei 5,  Jihui Wang 6,  Xiaomeng Ma 1,  Qiang Zhu 1,  Lili Li 1,  Xiuyun Zhu 1,  Yujiao Hou 4,  Shu Li 4,  Qing Dong 1,  Qing Tian 1,  Lulu Ai 1,  Wenjing Luo 1,  Mengyun Zuo 1,  Liping Shen 1,  Congyan Xie 1,  Hongzhong Song 4,  Ganlin Xu 5,  Kangdi Zheng 5,  Zhao Zhang 5,  Yongjun Lu 7,  Wei Qiu 1,  Tao Chen 5 8,  Andy Peng Xiang 9 3,  Zhengqi Lu 9
Affiliations

Affiliations

  • 1 Department of Neurology, Mental and Neurological Disease Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
  • 2 Center of Clinical Immunology, Mental and Neurological Disease Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
  • 3 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China.
  • 4 Department of Neurology, Yuedong Hospital, the Third Affiliated Hospital of Sun Yat-sen University, Meizhou, Guangdong 514011, China.
  • 5 South China Institute of Biomedicine, Guangzhou, Guangdong 510535, China.
  • 6 Department of Psychiatry, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
  • 7 Run Ze Laboratory for Gastrointestinal Microbiome Study, School of Life Sciences and Biomedical Center of Sun Yat-sen University, Guangzhou, Guangdong 510275, China.
  • 8 Center of Human Microecology Engineering and Technology of Guangdong Province, Guangzhou, Guangdong 510535, China.
  • 9 Department of Neurology, Mental and Neurological Disease Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China. [email protected] [email protected].
PMID: 33523954 DOI: 10.1126/sciadv.abe4827
Abstract

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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