Research progress on the microbiota-gut-brain axis in pathogenesis of neonatal hypoxic ischemic encephalopathy

doi:10.11852/zgetbjzz2019-1540

Abstract

Abstract: Neonatal hypoxic ischemic encephalopathy (HIE) is one of the diseases with high disability rate and mortality rate in the neonatal period.Recent studies have shown that the hypoxic ischemic injury of the newborn brain is related to the oxidative stress of the nervous system and mitochondrial dysfunction of tissue involved in the “microbiota-gut-brain axis”,but its molecular mechanism is still unclear.The most critical link of HIE is the occurrence of secondary energy failure,and the “latency period” between the two energy failure is the so-called “time window” for treatment,which is the best time when the neuroprotective measures to reduce brain injury can be successfully applied.This paper reviews the research progress on “microbiota-gut-brain axis” participating in oxidative stress in the pathogenesis of HIE,thereby providing a new dimension to the interaction between intestinal flora and brain,and opening a door for the prevention and treatment of HIE.

Key words: microbiota-gut-brain axis, neonatal hypoxic ischemic encephalopathy, oxidative stress, short chain fatty acids

摘要： 新生儿缺氧缺血性脑病 (HIE) 是新生儿期有较高致残率和致死率的疾病之一。近年来研究显示,新生儿脑部的缺氧缺血性损伤与微生物-肠-脑轴参与的神经系统氧化应激和组织线粒体功能障碍有关,但其分子机制尚不明确;且HIE最关键的环节是二次能量衰竭的发生,两次能量衰竭之间的“潜伏期”就是所谓的治疗“时间窗”,是减轻脑损伤的神经保护措施能被成功应用的最佳时间。本文综述了“微生物-肠-脑轴”参与氧化应激在HIE发病机制中的研究进展,希望通过该轴作用在HIE治疗“时间窗”内,减轻氧化应激对大脑的损伤,从而为肠道菌群与大脑之间的相互作用增加一个新的维度,为HIE的防治打开一扇门。

关键词: 微生物-肠-脑轴, 新生儿缺氧缺血性脑病, 氧化应激, 短链脂肪酸

CLC Number:

R722.1

LI Meng, HE Xue-jia, ZHU Wei-wei. Research progress on the microbiota-gut-brain axis in pathogenesis of neonatal hypoxic ischemic encephalopathy[J]. journal1, 2020, 28(11): 1223-1226.

李萌, 何学佳, 朱薇薇. 微生物-肠-脑轴在新生儿缺氧缺血性脑病发病机制中的研究进展[J]. 中国儿童保健杂志, 2020, 28(11): 1223-1226.

References

[1] 胡亚美,江载芳,申昆玲.诸福棠实用儿科学[M].8版.北京:人民卫生出版社,2013:469.
[2] Ni Y,Wang Z,Ma L,et al.Pilose antler polypeptides ameliorate inflammation and oxidative stress and improves gut microbiota in hypoxic-ischemic injured rats[J].Nutr Res,2019,64:93-108.
[3] Nonogaki K,Kaj T.Pharmacological stimulation of serotonin 5-HT1B receptors enhances increases in plasma active glucagon-like peptide-1 levels induced by dipeptidyl peptidase-4 inhibition independently of feeding in mice[J].Cell,2015,41(5):425-428.
[4] Williams B,van Benschoten A,Cimermancic P,et al.Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine[J].Cell Host & Microbe,2014,16(4):495-503.
[5] Latorre R,Sternini C,De Giorgio R,et al.Enteroendocrine cells:a review of their role in brain-gut communication[J].Neurogastroenterol Motil,2016,28(5):620-630.
[6] Nicolas1 GR,Chang PV.Deciphering the chemical lexicon of host-gut microbiota interactions[J].Trends Pharmacol Sci,2019,40(6):430-445.
[7] Deplancke B,Gaskins HR.Microbial modulation of innate defense:goblet cells and the intestinal mucus layer[J].Am J Clin Nutr,2001,73(Suppl 6):1131-1141.
[8] Bansil R,Turner BS.The biology of mucus:composition,syn thesis and organization[J].Adv Drug Deliv Rev,2018,124:3-15.
[9] Sgritta M,Dooling SW,Buffington SA,et al.Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder[J].Neuron,2019,101(2):246-259.
[10] Yuanyuan L,Benhua Z,Li Z,et al.Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus[J].Transl Psychiatry,2018,8(1):187-189.
[11] Patel M.Targeting oxidative stress in central nervous system disorders[J].Trends Pharmacol Sci,2016,37(9):768-778.
[12] Smaga I,Niedzielska E,Gawlik M,et al.Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders.Part 2.Depression,anxiety,schizophrenia and autism[J].Pharmacol Rep,2015,67(3):569-580.
[13] Dumitrescu L,Popescu-Olaru I,Cozma L,et al.Oxidative stress and the microbiota-gut-brain axis[J].Oxid Med Cell Longev,2018,2018:2406594.
[14] Bonaz B,Bazin T,Pellissier S.The vagus nerve at the interface of the microbiota-gut-brain axis[J].Front Neurosci,2018,12:49.
[15] Aridas J,Yawno T,Sutherland A,et al.Detecting brain injury in neonatal hypoxic ischemic encephalopathy:closing the gap between experimental and clinical research[J].Exp Neurol,2014,261:281-290.
[16] Olatz A,álvarez A,Miren R,et al.Role of antioxidants in neonatal hypoxic-ischemic brain injury:new therapeutic approaches[J].Int J Mol Sci,2017,18(2):265.
[17] Sanderson T,Reynolds C,Kumar R,et al.Molecular mechanisms of ischemia-reperfusion injury in brain:pivotal role of the mitochondrial membrane potential in reactive oxygen species generation[J].Mol Neurobiol,2013,47(1):9-23.
[18] Yang Y,Zhang X,Cui Y,et al.Apelin-13 protects the brain against ischemia/reperfusion injury through activating PI3K/Akt and ERK1/2 signaling pathways[J].Neurosci Lett,2014,568:44-49.
[19] Fanaei H,Karimian S,Sadeghipour R,et al.Testosterone enhances functional recovery after stroke through promotion of antioxidant defenses,BDNF levels and neurogenesis in male rats[J].Brain Res,2014,1558:74-83.
[20] Kim H,Leeds P,Chuang M,The HDAC inhibitor,sodium butyrate,stimulates neurogenesis in the ischemic brain[J].J Neurochem,2009,110(4):1226-1240.
[21] Russell WR,Hoyles L,Flint HJ,et al.Colonic bacterial metabolites and human health[J].Current Opinion in Microbiology,2013,16(3):246-254.
[22] Kelly C,Zheng L,Campbell E,et al.Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function[J].Cell Host & Microbe,2015,17(5):662-671.
[23] Khan JY,Black SM.Developmental changes in murine brain antioxidant enzymes[J].Pediatr Res,2003,54(1):77-82.
[24] Vadder F,Kovatcheva-Datchary P,Goncalves D,et al.Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits[J].Cell,2014,156(1-2):84-96.
[25] Beaumont M,Andriamihaja M,Lan A,et al.Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide:The adaptive response[J].Free Radic Biol Med,2016,93:155-164.
[26] Wu T,Yang L,Jiang J,et al.Chronic glucocorticoid treatment induced circadian clock disorder leads to lipid metabolism and gut microbiota alterations in rats[J].Life Sci,2018,192:173-182.
[27] Watkins C,Murphy K,Yen S,et al.Effects of therapeutic hypothermia on the gut microbiota and metabolome of infants suffering hypoxic-ischemic encephalopathy at birth[J].J Biochem Cell Biol,2019,26:105550.
[28] Nicolas GR,Chang PV.Deciphering the chemical lexicon of host-gut microbiota interactions[J].Trends Pharmacol Sci,2019,40(6):430-445.