Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (1): 62-80.doi: 10.4103/NRR.NRR-D-24-00917

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NLRP3 inflammasome and gut microbiota–brain axis: A new perspective on white matter injury after intracerebral hemorrhage

Xiaoxi Cai1, 2, #, Xinhong Cai1, 2, #, Quanhua Xie1, 2, #, Xueqi Xiao1, 2, Tong Li1, 2, Tian Zhou3, *, Haitao Sun1, 2, 3, *   

  1. 1 Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, The Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China;  2 Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China;  3 Key Laboratory of Mental Health of the Ministry of Education, Guangdong–Hong Kong–Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong Province, China
  • Online:2026-01-15 Published:2025-04-18
  • Contact: Haitao Sun, PhD, MD, 2009sht@smu.edu.cn; Tian Zhou, MD, tianzhou_tz@163.com
  • Supported by:
    This work was supported by the Guangdong Basic and Applied Basic Research Foundation, No. 2023A1515030045 (to HS); Presidential Foundation of Zhujiang Hospital of Southern Medical University, No. yzjj2022ms4 (to HS).

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Abstract: Intracerebral hemorrhage is the most dangerous subtype of stroke, characterized by high mortality and morbidity rates, and frequently leads to significant secondary white matter injury. In recent decades, studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis. This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury. The NACHT, LRR, and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in this context. This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome. These mechanisms include metabolic pathways (involving short-chain fatty acids, lipopolysaccharides, lactic acid, bile acids, trimethylamine-N-oxide, and tryptophan), neural pathways (such as the vagus nerve and sympathetic nerve), and immune pathways (involving microglia and T cells). We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage. The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier, inducing neuroinflammation, and interfering with nerve regeneration. Finally, we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury. Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage, paving the way for exploring potential therapeutic approaches.

Key words: gut microbiota, gut microbiota–brain axis, immune, intracerebral hemorrhage, neuroinflammation, NLRP3 protein, stroke, therapeutics, white matter injury