The Journal of Practical Medicine >

2025 , Vol. 41 >Issue 6: 911 - 915

DOI: https://doi.org/10.3969/j.issn.1006-5725.2025.06.021

Reviews

Impact of microbiota⁃gut⁃brain axis on neuroinflammation after post⁃cardiac arrest brain injury

  • Haojun ZHANG ,
  • Mei JING ,
  • Yufeng ZHU ,
  • Tianpeng XU ,
  • Xi CHEN ,
  • Rongyi SHI ,
  • Yi. SHAN
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  • Department of Emergency，Naval Medical Center，Shanghai 200052，Shanghai，China

Received date: 2024-12-02

  Online published: 2025-03-31

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Abstract

Cardiac arrest is a major health event that poses a major threat to human life and health. Post-cardiac arrest brain injury is the main adverse prognostic factor and cause of death in patients who experience cardiac arrest. Currently， the therapeutic methods and effects are limited. In recent years， with the in-depth research on microbiota-gut-brain communication， it has been found that intestinal microbiota and their metabolites may play a role in the regulation of neuroinflammation in post-cardiac arrest brain injury. Short-chain fatty acids are the key substances in microbiota-gut-brain communication， and the mechanism involves immune， endocrine and neuroregulatory pathways. Supplementation of short-chain fatty acid-producing bacteria or short-chain fatty acids can improve intestinal flora disorder and reduce neuroinflammation after cardiopulmonary resuscitation. As a key mediator in microbial-gut-brain communication， short-chain fatty acids have great potential for the treatment of brain injury after cardiac arrest. This review explores the role and regulatory mechanism of microbiota-gut-brain communication in the neuroinflammation of brain injury after cardiopulmonary resuscitation through immune， endocrine and neuroregulatory pathways， providing a new idea for the treatment of post-cardiac arrest brain injury.

Key words： cardiac arrest; post-cardiac arrest brain injury; short-chain fatty acid; microbiota-gut-brain axis

Cite this article

Haojun ZHANG , Mei JING , Yufeng ZHU , Tianpeng XU , Xi CHEN , Rongyi SHI , Yi. SHAN . Impact of microbiota⁃gut⁃brain axis on neuroinflammation after post⁃cardiac arrest brain injury[J]. The Journal of Practical Medicine, 2025 , 41(6) : 911 -915 . DOI: 10.3969/j.issn.1006-5725.2025.06.021

References

1 GREIF R， BHANJI F， BIGHAM B L， et al. Education， Implementation， and Teams： 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations ［J］. Resuscitation， 2020，156： A188-A239.
2 SOAR J， BERG K M， ANDERSEN L W， et al. Adult Advanced Life Support： 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations ［J］. Resuscitation， 2020，156： A80-A119.
3 PERKINS G D， CALLAWAY C W， HAYWOOD K， et al. Brain injury after cardiac arrest ［J］. Lancet， 2021，398（10307）： 1269-1278. doi:10.1016/s0140-6736(21)00953-3
4 BALU R， RAJAGOPALAN S， BAGHSHOMALI S， et al. Cerebrovascular pressure reactivity and intracranial pressure are associated with neurologic outcome after hypoxic-ischemic brain injury ［J］. Resuscitation， 2021，164： 114-121. doi:10.1016/j.resuscitation.2021.04.023
5 KJAERGAARD J， M?LLER J E， SCHMIDT H， et al. Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest ［J］. N Engl J Med， 2022，387（16）： 1456-1466. doi:10.1056/nejmoa2208687
6 SCHMIDT H， KJAERGAARD J， HASSAGER C， et al. Oxygen Targets in Comatose Survivors of Cardiac Arrest ［J］. N Engl J Med， 2022，387（16）： 1467-1476.
7 PERKINS G D， NEUMAR R， HSU C H， et al. Improving Outcomes After Post-Cardiac Arrest Brain Injury： A Scientific Statement From the International Liaison Committee on Resuscitation ［J］. Circulation， 2024.doi： 10.1161/CIR.0000000000001219 . Online ahead of print.
8 SANDRONI C， CRONBERG T， SEKHON M. Brain injury after cardiac arrest： Pathophysiology， treatment， and prognosis ［J］. Intensive Care Med， 2021，47（12）： 1393-1414. doi:10.1007/s00134-021-06548-2
9 MEYER M A S， WIBERG S， GRAND J， et al. Treatment Effects of Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response After Out-of-Hospital Cardiac Arrest （The IMICA Trial）： A Double-Blinded， Placebo-Controlled， Single-Center， Randomized， Clinical Trial ［J］. Circulation， 2021， 143（19）： 1841-1851. doi:10.1161/circulationaha.120.053318
10 奚可欣， 赵宇骐， 谢晓婷， 等. 肠道菌群对胶质瘤的调控作用研究进展 ［J］. 实用医学杂志， 2024，40（14）： 2027-2030.
11 MORAIS L H， SCHREIBER H L T， MAZMANIAN S K. The gut microbiota-brain axis in behaviour and brain disorders ［J］. Nat Rev Microbiol， 2021，19（4）： 241-255. doi:10.1038/s41579-020-00460-0
12 HOILAND R L， AINSLIE P N， WELLINGTON C L， et al. Brain Hypoxia Is Associated With Neuroglial Injury in Humans Post–Cardiac Arrest ［J］. Circ Res， 2021，129（5）： 583-597. doi:10.1161/circresaha.121.319157
13 OUSTA A， PIAO L， FANG Y H， et al. Microglial Activation and Neurological Outcomes in a Murine Model of Cardiac Arrest ［J］. Neurocrit Care， 2022，36（1）： 61-70. doi:10.1007/s12028-021-01253-w
14 WANG M， PAN W， XU Y， et al. Microglia-Mediated Neuroinflammation： A Potential Target for the Treatment of Cardiovascular Diseases ［J］. J Inflamm Res， 2022，15： 3083-3094. doi:10.2147/jir.s350109
15 CHANG Y， ZHU J， WANG D， et al. NLRP3 inflammasome-mediated microglial pyroptosis is critically involved in the development of post-cardiac arrest brain injury ［J］. J Neuroinflammation， 2020，17（1）： 219. doi:10.1186/s12974-020-01879-1
16 ZHENG G， HE F， XU J， et al. The Selective NLRP3-inflammasome inhibitor MCC950 Mitigates Post-resuscitation Myocardial Dysfunction and Improves Survival in a Rat Model of Cardiac Arrest and Resuscitation ［J］. Cardiovasc Drugs Ther， 2023，37（3）： 423-433. doi:10.1007/s10557-021-07282-z
17 LINNERBAUER M， WHEELER M A， QUINTANA F J. Astrocyte Crosstalk in CNS Inflammation ［J］. Neuron， 2020，108（4）： 608-622. doi:10.1016/j.neuron.2020.08.012
18 SHEN X Y， GAO Z K， HAN Y， et al. Activation and Role of Astrocytes in Ischemic Stroke ［J］. Front Cell Neurosci， 2021，15： 755955. doi:10.3389/fncel.2021.755955
19 LING Y， GONG T， ZHANG J， et al. Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke ［J］. Front Aging Neurosci， 2020，12： 511562. doi:10.3389/fnagi.2020.511562
20 YU S， XU J， WU C， et al. Multi-omics Study of Hypoxic-Ischemic Brain Injury After Cardiopulmonary Resuscitation in Swine ［J］. Neurocrit Care， 2024.doi： 10.1007/s12028-024-02038-7 . Online ahead of print.
21 YUAN Q， SUN L， MA G， et al. Alterations of the gut microbial community structure modulates the Th17 cells response in a rat model of asphyxial cardiac arrest ［J］. Biochem Biophys Rep， 2023，35： 101543. doi:10.1016/j.bbrep.2023.101543
22 LI X， YIN X， PANG J， et al. Hydrogen sulfide inhibits lipopolysaccharide-based neuroinflammation-induced astrocyte polarization after cerebral ischemia/reperfusion injury ［J］. Eur J Pharmacol， 2023，949： 175743. doi:10.1016/j.ejphar.2023.175743
23 WENZEL T J， GATES E J， RANGER A L， et al. Short-chain fatty acids （SCFAs） alone or in combination regulate select immune functions of microglia-like cells ［J］. Mol Cell Neurosci， 2020，105： 103493. doi:10.1016/j.mcn.2020.103493
24 MARTINEZ M， YU W， MENDEN H L， et al. Butyrate suppresses experimental necrotizing enterocolitis-induced brain injury in mice ［J］. Front Pediatr， 2023，11： 1284085. doi:10.3389/fped.2023.1284085
25 XIAO W， SU J， GAO X， et al. The microbiota-gut-brain axis participates in chronic cerebral hypoperfusion by disrupting the metabolism of short-chain fatty acids ［J］. Microbiome， 2022，10（1）： 62. doi:10.1186/s40168-022-01255-6
26 LI T T， ZHAO D M， WEI Y T， et al. Effect and Mechanism of Sodium Butyrate on Neuronal Recovery and Prognosis in Diabetic Stroke ［J］. J Neuroimmune Pharmacol， 2023，18（3）： 366-382. doi:10.1007/s11481-023-10071-0
27 YUAN C， SHI L， SUN Z， et al. Regulatory T cell expansion promotes white matter repair after stroke ［J］. Neurobiol Dis， 2023，179： 106063. doi:10.1016/j.nbd.2023.106063
28 MARTIN-GALLAUSIAUX C， MARINELLI L， BLOTTIèRE H M， et al. SCFA： Mechanisms and functional importance in the gut ［J］. Proc Nutr Soc， 2021，80（1）： 37-49. doi:10.1017/s0029665120006916
29 SCHONFELD P， WOJTCZAK L. Short- and medium-chain fatty acids in energy metabolism： The cellular perspective ［J］. J Lipid Res， 2016，57（6）： 943-954. doi:10.1194/jlr.r067629
30 MITCHELL R W， ON N H， DEL BIGIO M R， et al. Fatty acid transport protein expression in human brain and potential role in fatty acid transport across human brain microvessel endothelial cells ［J］. J Neurochem， 2011，117（4）： 735-746.
31 SADLER R， CRAMER J V， HEINDL S， et al. Short-Chain Fatty Acids Improve Poststroke Recovery via Immunological Mechanisms ［J］. J Neurosci， 2020，40（5）： 1162-1173. doi:10.1523/jneurosci.1359-19.2019
32 SILVA Y P， BERNARDI A， FROZZA R L. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication ［J］. Front Endocrinol （Lausanne）， 2020，11： 25. doi:10.3389/fendo.2020.00025
33 ZHOU Z， XU N， MATEI N， et al. Sodium butyrate attenuated neuronal apoptosis via GPR41/Gβγ/PI3K/Akt pathway after MCAO in rats ［J］. J Cereb Blood Flow Metab， 2021，41（2）： 267-281. doi:10.1177/0271678x20910533
34 WEI H， YU C， ZHANG C， et al. Butyrate ameliorates chronic alcoholic central nervous damage by suppressing microglia-mediated neuroinflammation and modulating the microbiome-gut-brain axis ［J］. Biomed Pharmacother， 2023，160： 114308. doi:10.1016/j.biopha.2023.114308
35 MA B D Y， CHAN T Y H， LO B W Y. Unveiling the hidden culprit： How the brain-gut axis fuels neuroinflammation in ischemic stroke ［J］. Surg Neurol Int， 2024，15： 394. doi:10.25259/sni_703_2024
36 PASOKH A， FARZIPOUR M， MAHMOUDI J， et al. The effect of fecal microbiota transplantation on stroke outcomes： A systematic review ［J］. J Stroke Cerebrovasc Dis， 2022，31（11）： 106727. doi:10.1016/j.jstrokecerebrovasdis.2022.106727
37 BENAKIS C， LIESZ A. The gut-brain axis in ischemic stroke： Its relevance in pathology and as a therapeutic target ［J］. Neurol Res Pract， 2022，4（1）： 57. doi:10.1186/s42466-022-00222-8
38 WANG X， SUN Z， YANG T， et al. Sodium butyrate facilitates CRHR2 expression to alleviate HPA axis hyperactivity in autism-like rats induced by prenatal lipopolysaccharides through histone deacetylase inhibition ［J］. mSystems， 2023，8（4）： e0041523. doi:10.1128/msystems.00915-23
39 REN Q， HE C， SUN Y， et al. Asiaticoside improves depressive-like behavior in mice with chronic unpredictable mild stress through modulation of the gut microbiota ［J］. Front Pharmacol， 2024，15： 1461873. doi:10.3389/fphar.2024.1461873
40 ZHAO Q， SHEN Y， LI R， et al. Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression ［J］. J Cereb Blood Flow Metab， 2021，41（5）： 1091-1102. doi:10.1177/0271678x20948612
41 HASSAMAL S. Chronic stress， neuroinflammation， and depression： An overview of pathophysiological mechanisms and emerging anti-inflammatories ［J］. Front Psychiatry， 2023，14： 1130989. doi:10.3389/fpsyt.2023.1130989
42 MARTEL J， CHANG S H， KO Y F， et al. Gut barrier disruption and chronic disease ［J］. Trends Endocrinol Metab， 2022，33（4）： 247-265. doi:10.1016/j.tem.2022.01.002
43 CONN K A， BORSOM E M， COPE E K. Implications of microbe-derived ?-aminobutyric acid （GABA） in gut and brain barrier integrity and GABAergic signaling in Alzheimer's disease ［J］. Gut Microbes， 2024，16（1）： 2371950. doi:10.1080/19490976.2024.2371950
44 MADISON A A， BAILEY M T. Stressed to the Core： Inflammation and Intestinal Permeability Link Stress-Related Gut Microbiota Shifts to Mental Health Outcomes ［J］. Biol Psychiatry， 2024，95（4）： 339-347. doi:10.1016/j.biopsych.2023.10.014
45 PAN I， ISSAC P K， RAHMAN M M， et al. Gut-Brain Axis a Key Player to Control Gut Dysbiosis in Neurological Diseases ［J］. Mol Neurobiol， 2024，61（12）： 9873-9891. doi:10.1007/s12035-023-03691-3
46 KAKINUMA Y. Significance of vagus nerve function in terms of pathogenesis of psychosocial disorders ［J］. Neurochem Int， 2021，143： 104934. doi:10.1016/j.neuint.2020.104934
47 WANG Y， TAN Q， PAN M， et al. Minimally invasive vagus nerve stimulation modulates mast cell degranulation via the microbiota-gut-brain axis to ameliorate blood-brain barrier and intestinal barrier damage following ischemic stroke ［J］. Int Immunopharmacol， 2024，132： 112030. doi:10.1016/j.intimp.2024.112030
48 XIE J， BRUGGEMAN A， DE NOLF C， et al. Gut microbiota regulates blood-cerebrospinal fluid barrier function and Aβ pathology ［J］. Embo J， 2023，42（17）： e111515. doi:10.15252/embj.2022111515
49 ANDERSEN L W， LIND P C， VAMMEN L， et al. Adult post-cardiac arrest interventions： An overview of randomized clinical trials ［J］. Resuscitation， 2020，147： 1-11. doi:10.1016/j.resuscitation.2019.12.003
50 刘远山， 余凯， 黄子通， 等. 利用模拟人研究操作者疲劳和心肺复苏质量相关性 ［J］. 实用医学杂志， 2020，36（24）： 3430-3433.
51 李星明， 孙广琦， 郑雯， 等. 心肺复苏后昏迷患者神经功能预后生物标志物的研究进展 ［J］. 实用休克杂志（中英文）， 2024，8（5）： 290-298.
52 姚准， 赵元瑞， 余追. 心搏骤停后脑损伤的病理生理改变的研究进展 ［J］. 卒中与神经疾病， 2024，31（3）： 302-306.
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