Article(id=1208862373352444330, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208862365714616539, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2021.09.05, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1613318400000, receivedDateStr=2021-02-15, revisedDate=1621440000000, revisedDateStr=2021-05-20, acceptedDate=null, acceptedDateStr=null, onlineDate=1766144849384, onlineDateStr=2025-12-19, pubDate=1632758400000, pubDateStr=2021-09-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766144849384, onlineIssueDateStr=2025-12-19, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766144849384, creator=13701087609, updateTime=1766144849384, updator=13701087609, issue=Issue{id=1208862365714616539, tenantId=1146029695717560320, journalId=1189873630562394117, year='2021', volume='46', issue='9', pageStart='849', pageEnd='953', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1766144847562, creator=13701087609, updateTime=1766144914151, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1208862645055254758, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208862365714616539, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1208862645055254759, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208862365714616539, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=871, endPage=875, ext={EN=ArticleExt(id=1208862373897703867, articleId=1208862373352444330, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Research status of gut microbiota and stress and its application in military stress, columnId=1208862370294788358, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Special Issues on Intestinal Flora and Disease Progression, runingTitle=null, highlight=null, articleAbstract=

Stress is a non-specific response of the body when suffering from internal or external factors. It is involved in the development and progression of many physical and mental diseases such as irritable bowel syndrome, functional gastrointestinal diseases, anxiety and depression. It is the main cause of non-combat attrition. Gut microbiota can regulate the body's metabolism,immune and nervous system development and functions through the gut microbiota-gut-brain axis and affect the health and behavior. The interaction between its composition and function and stress-related diseases is gradually being revealed. The intervention and regulation of gut microbiota may become a new solution to prevent and treat stress-related diseases and participate in influencing the reaction of military personnel to military stress. This review focuses on the research progress of stress-related mechanisms, gut microbiota characteristics and related intervention research, the study status of military stress-related and gut microbiota and the prospects of its application.

, correspAuthors=Zi-Kai Wang, authorNote=null, correspAuthorsNote=
*E-mail:
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应激是机体受到内外环境刺激时产生的非特异性反应,参与肠易激综合征、功能性胃肠病、焦虑及抑郁等诸多身心疾病的发生发展,是非战斗减员的主要原因。肠道微生态可通过肠道菌群-肠-脑轴调节机体代谢、免疫及神经系统的发育及功能,影响机体健康及行为,其构成及功能与应激相关疾病的相互作用正逐渐被揭示。肠道微生态的干预及调节或可成为预防及治疗应激相关疾病的新方案,可用于干预军人对军事应激的反应。该文主要从应激反应发生机制、肠道微生态特征及其干预、军事应激相关肠道微生态研究的现状及其应用等方面进行概述。

, correspAuthors=王子恺, authorNote=null, correspAuthorsNote=
王子恺,E-mail:
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张娜娜,医学博士,主要从事肠道微生态方面的研究

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肠道微生态与应激反应的关系及其在军事应激中的应用
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张娜娜 1, 2 , 杨云生 2 , 王子恺 2, *
解放军医学杂志 | 肠道菌群与疾病的关系研究进展专题 2021,46(9): 871-875
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解放军医学杂志 | 肠道菌群与疾病的关系研究进展专题 2021, 46(9): 871-875
肠道微生态与应激反应的关系及其在军事应激中的应用
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张娜娜1, 2, 杨云生2, 王子恺2, *
作者信息
  • 1解放军医学院,北京 100853
  • 2解放军总医院第一医学中心消化内科医学部,北京 100853
  • 张娜娜,医学博士,主要从事肠道微生态方面的研究

通讯作者:

王子恺,E-mail:
Research status of gut microbiota and stress and its application in military stress
Na-Na Zhang1, 2, Yun-Sheng Yang2, Zi-Kai Wang2, *
Affiliations
  • 1Medical School of Chinese PLA, Beijing 100853, China
  • 2Center for Gastroenterology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
出版时间: 2021-09-28 doi: 10.11855/j.issn.0577-7402.2021.09.05
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应激是机体受到内外环境刺激时产生的非特异性反应,参与肠易激综合征、功能性胃肠病、焦虑及抑郁等诸多身心疾病的发生发展,是非战斗减员的主要原因。肠道微生态可通过肠道菌群-肠-脑轴调节机体代谢、免疫及神经系统的发育及功能,影响机体健康及行为,其构成及功能与应激相关疾病的相互作用正逐渐被揭示。肠道微生态的干预及调节或可成为预防及治疗应激相关疾病的新方案,可用于干预军人对军事应激的反应。该文主要从应激反应发生机制、肠道微生态特征及其干预、军事应激相关肠道微生态研究的现状及其应用等方面进行概述。

应激  /  肠道微生态  /  肠-脑轴  /  军事

Stress is a non-specific response of the body when suffering from internal or external factors. It is involved in the development and progression of many physical and mental diseases such as irritable bowel syndrome, functional gastrointestinal diseases, anxiety and depression. It is the main cause of non-combat attrition. Gut microbiota can regulate the body's metabolism,immune and nervous system development and functions through the gut microbiota-gut-brain axis and affect the health and behavior. The interaction between its composition and function and stress-related diseases is gradually being revealed. The intervention and regulation of gut microbiota may become a new solution to prevent and treat stress-related diseases and participate in influencing the reaction of military personnel to military stress. This review focuses on the research progress of stress-related mechanisms, gut microbiota characteristics and related intervention research, the study status of military stress-related and gut microbiota and the prospects of its application.

stress  /  gut microbiota  /  the gut-brain axis  /  military
张娜娜, 杨云生, 王子恺. 肠道微生态与应激反应的关系及其在军事应激中的应用. 解放军医学杂志, 2021 , 46 (9) : 871 -875 . DOI: 10.11855/j.issn.0577-7402.2021.09.05
Na-Na Zhang, Yun-Sheng Yang, Zi-Kai Wang. Research status of gut microbiota and stress and its application in military stress[J]. Medical Journal of Chinese People’s Liberation Army, 2021 , 46 (9) : 871 -875 . DOI: 10.11855/j.issn.0577-7402.2021.09.05
应激是机体受到内外环境刺激时所发生的非特异性反应,长期持续的慢性应激可引起体重减轻、代谢失调、肠易激综合征、结肠炎,以及焦虑、抑郁等神经心理疾病[1-3]。除下丘脑-垂体-肾上腺皮质(HPA)轴及交感神经轴这两大应激反应通路外,肠-脑(GBA)轴通过迷走神经、肠内分泌及免疫等功能实现肠道与脑之间的双向交流通路,是应激相关机体反应的第三大潜在通路。以往研究发现,应激与肠道微生态构成改变存在相关性[4],肠道微生态可能是应激相关有害效应的关键因子[5]。通过调节肠道微生态来缓解应激相关不良反应或治疗应激相关疾病,提升军队人员作战能力是新时期军事背景下增强人体效能的重要研究方向。本文主要就目前应激机制研究进展、应激相关肠道菌群特征及微生态干预、军事应激背景下肠道微生态研究的现状及前景等进行综述。
交感肾上腺髓质轴、HPA轴与应激存在关联[6]。当机体遭受应激刺激时,自主神经系统首先被激活,引起心率加快等一系列自主神经紊乱症状,然后HPA轴被激活,促进促皮质激素释放激素、促肾上腺皮质激素释放激素及糖皮质激素等一系列激素的释放,并作用于机体靶器官,参与生理进程,影响机体代谢,对应激刺激做出应答。炎症反应机制于20多年前被提出,该学说认为应激相关疾病与应激诱导的系统性炎症反应存在相关性[7]。应激时可出现C反应蛋白、肿瘤坏死因子α、白细胞介素(IL)-6及IL-2等炎性因子水平升高[8],且与应激相关的精神心理失衡如焦虑、抑郁及创伤后应激障碍(PTSD)等呈正相关[9-10]。肾素血管紧张素系统(renin-angiotensin system,RAS)也被发现与应激反应相关[11]。目前普遍认为应激反应是上述各种机制综合作用的结果,HPA轴与RAS系统共同受神经递质、神经肽类调节,且与体内的炎症反应相互影响。
肠道菌群直接或通过其代谢物间接与机体相互作用以维持肠道微生态的平衡,参与调节机体免疫功能、代谢、精神健康甚至神经系统的发育,有人体的“第二大脑”之称[1]。研究发现,肠道微生态失衡与肠易激综合征、代谢综合征、焦虑综合征、抑郁综合征等多种疾病的发生及进展相关。应激刺激引起的一系列躯体症状及行为心理变化与肠道微生态失衡的相互关系目前已有研究报道,认为应激可引起肠道微生态构成及功能改变,这种变化与肠屏障功能失调、肠黏膜通透性增加相关[12]。肠黏膜通透性增加使细菌自身成分如脂多糖或其有害代谢物易位,进入血液循环,激活机体免疫系统,促进炎症反应发生,肠屏障功能进一步失调,导致应激相关的躯体症状如胃肠功能失调、营养吸收及代谢异常,增加了机体患病及感染的风险。应激相关精神心理及行为学失调的关键通路是GBA轴。肠道微生态可通过化学信号分子、神经信号通路及免疫系统来调节中枢神经系统的功能。短链脂肪酸由肠道内的细菌代谢膳食纤维产生,可直接通过调节神经元可塑性及基因表达作用于中枢神经系统来调节机体行为。研究发现,给小鼠补充丁酸盐可缓解其抑郁行为[13]。此外,肠道菌群还可代谢色氨酸产生5-羟色胺(5-HT),或代谢谷氨酸产生γ-氨基丁酸(GABA),5-HT、GABA作为重要的神经递质,参与调节焦虑及抑郁样行为。给大鼠补充鼠李糖乳杆菌可增加其体内GABA含量,减轻其焦虑及抑郁行为[13]。迷走神经是GBA的主要神经信号通路,肠神经系统可感知胃肠道的感觉信号如肠腔容积变化等,通过迷走神经传递至中枢神经,使机体产生适应性反应,切除迷走神经后,鼠李糖乳杆菌JB-1补充的有益效应消失[14]。在应激刺激下,小胶质细胞的功能往往发生改变,而肠道微生态的存在是脑内小胶质细胞、固有免疫细胞发育、成熟及激活的必要条件。Erny等[15]研究发现,无菌小鼠脑内不成熟的小胶质细胞数目明显增加。因此,肠道微生态可能通过调节小胶质细胞功能来影响机体对应激刺激的反应。现阶段,应激相关肠道微生态机制的研究主要集中于无菌小鼠等动物模型,后续需要通过人体研究来进一步证实。
目前研究发现,维持肠道微生态的平衡对于机体应对应激刺激至关重要。应激引起的肠道微生态失衡可加重机体炎症状态,慢性应激的存在促进了溃疡性结肠炎小鼠肠道内螺杆菌属、消化链球菌科、链球菌属及粪肠球菌等促炎菌的过度生长,与加重的炎症反应相关[16]。应激引起的相关表型特征也可通过肠道微生态传递,将经受慢性轻度不可预见性应激(UCMS)小鼠的肠道菌群移植给抗生素处理后的受体小鼠,可引起受体小鼠出现相应的抑郁及焦虑表现,且受体小鼠的乳酸杆菌丰度降低,Akkermansia菌丰度增加,与供体小鼠菌群特征类似[17]。有病例对照研究发现,应激相关焦虑障碍患者的肠道菌群α多样性及数目减少,厚壁菌门及柔壁菌门丰度降低[18],产生短链脂肪酸的细菌减少,而埃希菌属-志贺菌、梭杆菌属及活泼瘤胃球菌过度生长[19];病情严重者产粪甾醇真杆菌亚组、瘤胃球菌UCG-014及普雷沃氏菌-9丰度更低,拟杆菌属及埃希菌属-志贺菌丰度更高[18]。虽然应激引起的肠道微生态构成改变可在停止应激刺激后恢复正常,但其相应的代谢谱变化可能会持续存在。一项针对幼龄期大鼠慢性应激的研究发现,慢性应激停止后,大鼠肠道菌群相对丰度可自行恢复,但肠道菌群相关代谢产物如天冬氨酸、乳酸盐、鸟氨酸等含量升高,且可一直持续至成年期[20]
肠道微生态可能是机体对应激做出应答的重要调节因子,但因研究对象、测序及分析方法的差异,不同研究间存在较大的异质性。另外,目前的研究多为横断面、小样本量的研究,缺乏随机对照的设计方案,未来有必要设计更长期、样本量更大的研究,尽量控制各种混杂因素[5]
微生态制剂包括益生菌、益生元及合生元等。补充微生态制剂可通过调节肠道微生态来改善应激状态。有研究给予斑马鱼补充L. plantarum改变了其肠道菌群的多样性,缓解其焦虑样行为,防止应激引起的肠道微生态失衡[21]。有研究给予UCMS大鼠补充长链双歧杆菌或鼠李糖杆菌等益生菌,或补充低聚果糖及低聚葡萄糖等益生元,均可缓解其应激相关的体重减轻及抑郁样行为,推测其作用机制与色氨酸代谢通路有关[22]。有研究对健康青年人连续24周补充格氏乳杆菌CP2305菌株,结果显示可改善其精神状态、睡眠质量及应激状态下的肠道微生态[23]。有研究对47例医学院大学生进行连续8周的干酪乳杆菌代田株补充,发现可缓解压力应激引起的腹部症状,维持肠道微生态的多样性[24]。除了补充单株益生菌外,也有研究通过补充混合益生菌预防应激带来的不良反应,如给黄鳝补充混合芽孢杆菌增强了其对低氧刺激的耐受力[25],给条纹鲇鱼补充解淀粉芽孢杆菌54A及短小芽孢杆菌47B的混合益生菌,结果发现鲇鱼对应激的耐受性增加[26],给健康大学生补充多种益生菌后,其焦虑情绪及忧虑症状缓解,对负面情绪的调节能力增强[27]
肠微生态制品移植(FMT)作为一种新的改变肠道微生态的方式,在溃疡性结肠炎等肠道炎症性疾病[28]、阿尔茨海默病等神经系统疾病[29]、孤独症谱系障碍等精神心理疾病[30]中的应用已有报道。有研究将健康大鼠的肠道菌群移植给接受慢性轻度应激的大鼠,结果发现其可改善应激引起的脑功能异常[31],移植给脊柱受损大鼠可预防脊柱损伤引起的焦虑表现[32]。以上研究提示FMT在改善应激及其相关疾病方面具有重要的潜在价值,但目前相关的动物及临床随机对照研究较少[33]。机体应激抵抗力及应激后恢复力相关的肠道微生态调节研究具有重要的价值及现实意义。
军队人员作为一个特殊群体,受到军事训练及作战等强烈应激因子的刺激后,可出现不同程度的生理及心理损伤,这种特殊的军事环境及军事任务引起军人产生的生理、心理等非特异性反应被称为军事应激[34]。军事应激因其应激源强度大、应激人群规模大、应激反应形式多样及应激损伤处理原则特殊等特征,可导致战场认知错误、武器操控失能及战斗精神病,是引起部队非战斗减员的重要原因[35]。美国军队人员的PTSD发生率为4%~31%[36],伊拉克及阿富汗战争后的退伍军人PTSD发生率达23%[36]。我国高寒地区军人抑郁症状发生率达37.5%[37]。因此,如何增强军人对军事应激的耐受力并在应激源刺激后恢复战斗力是军事医学面临的重要课题。
由于军人群体的特殊性及军事活动的复杂性,军事应激形式多样且复杂。现有军事应激研究人群主要以接受各种军事任务及训练的官兵为对象,如将潜艇及装甲车官兵纳入极端封闭环境应激对机体影响的研究[38]。其他动物模型包括:利用啮齿类动物睡眠剥夺模型研究睡眠剥夺对认知、情绪等的影响[39];利用热应激或冷刺激实验动物模型探索温度变化对机体的影响;利用疲劳应激模型探索疲劳状态对机体作业能力的影响[40]等。但目前的军事应激模型均以特定类型的应激相关疾病为主,缺乏多种军事应激源同时存在或模拟战争环境条件下的动物模型,这在一定程度上限制了军事应激相关研究的开展。
现阶段,各种军事应激状态下的肠道菌群结构及功能特征,相关肠道菌群-肠-脑轴机制,以及肠道微生态干预研究仍匮乏。2017年,有研究报道持续4 d野外行军士兵的肠道菌群α多样性增加,拟杆菌属的相对丰度下降,体内非优势菌属的相对丰度增加,菌群代谢谱改变,粪便中半胱氨酸增加[12]。最近,有研究发现补充含乳酸杆菌、双歧杆菌及菊粉的微生态制剂可改善野外驻训军人的紧张及困倦程度,缓解胃肠道症状,有助于其在高强度军事应激下进行决策[41]。未来有必要开展不同训练及作战模式、各种极端环境下的军事应激相关肠道微生态特征、机制及干预研究,明确军事应激相关肠道菌群的特征及其作用机制,证实军事应激微生态干预手段的有效性及安全性。
机体健康状态受各种应激源扰动,在应激源刺激下维持稳态、快速修复受损组织及器官是机体健康的重要标志。不同军事训练、作战及极端环境等可导致军人出现不同程度的军事应激,是军事医学面临的重要课题。肠道微生态稳态的维持及恢复有助于维持机体心理及生理功能的稳定,增强机体的应激抵抗力及恢复力,防止各种应激相关疾病的发生,肠道菌群-肠-脑轴通路在其中发挥重要作用。微生态制剂及菌群移植等微生态干预是恢复并维持肠道稳态、预防及治疗应激相关疾病的手段。军事应激相关肠道微生态研究可为提升部队官兵人体效能及战斗力提供支撑,但需深入开展军事应激相关肠道菌群宏基因组、培养组、代谢组、转录组及蛋白质组等多组学分析,肠道菌群-肠-脑轴具体机制研究,以及体内外试验的验证研究。
  • 国防科技委创新培育课题(1716312ZT00204801)
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2021年第46卷第9期
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doi: 10.11855/j.issn.0577-7402.2021.09.05
  • 接收时间:2021-02-15
  • 首发时间:2025-12-19
  • 出版时间:2021-09-28
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  • 收稿日期:2021-02-15
  • 修回日期:2021-05-20
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Innovation Incubation Project of National Defense Science and Technology Commission(1716312ZT00204801)
国防科技委创新培育课题(1716312ZT00204801)
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    1解放军医学院,北京 100853
    2解放军总医院第一医学中心消化内科医学部,北京 100853

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王子恺,E-mail:
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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