Article(id=1194613945832022189, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194613942065533315, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.0941.2025.0121, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1719417600000, receivedDateStr=2024-06-27, revisedDate=null, revisedDateStr=null, acceptedDate=1722700800000, acceptedDateStr=2024-08-04, onlineDate=1762747759539, onlineDateStr=2025-11-10, pubDate=1743091200000, pubDateStr=2025-03-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1762747759539, onlineIssueDateStr=2025-11-10, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1762747759539, creator=13701087609, updateTime=1762747759539, updator=13701087609, issue=Issue{id=1194613942065533315, tenantId=1146029695717560320, journalId=1189873630562394117, year='2025', volume='50', issue='3', pageStart='245', pageEnd='365', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1762747758641, creator=13701087609, updateTime=1762749141462, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1194619742100103439, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194613942065533315, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1194619742100103440, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194613942065533315, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=284, endPage=291, ext={EN=ArticleExt(id=1194613946117234866, articleId=1194613945832022189, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Research progress of the relationship between gut microbiota and systemic lupus erythematosus, columnId=1194613943957164424, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Special Issue on Role of Gut Microbiota in Disease Occurrence and Treatment, runingTitle=null, highlight=null, articleAbstract=

Systemic lupus erythematosus (SLE) is a chronic diffuse connective tissue disease characterized by abnormal activation of the immune system, which attacks the body's tissues. It has a complex course and its pathological basis is vasculitis. In recent years, research on the relationship between SLE and the gut microbiota has increased significantly, but how to regulate the gut microbiota for the treatment of SLE remains unclear. Studies have found that the intestinal microbiota of SLE patients differs from that of healthy people in terms of Firmicutes, Bacteroidetes, Actinomycetes, and Proteobacteria, etc., and this has been verified in animal experiments. In this review, the changes of intestinal microbiota in SLE patients and their association with the pathogenesis and progression of the disease are systematically reviewed, aiming to provide new insights into the treatment of SLE.

, correspAuthors=Bin Zhang, authorNote=null, correspAuthorsNote=
E-mail:
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系统性红斑狼疮(SLE)是一种免疫系统异常激活后攻击自身组织导致的慢性弥漫性结缔组织病;其病程复杂,以血管炎为病理基础。近年来,关于SLE与肠道菌群关系的研究明显增多,但具体如何调节肠道菌群以治疗SLE尚未明确。研究发现,SLE患者的肠道菌群与健康人群在厚壁菌门、拟杆菌门、放线菌门、变形菌门等方面存在差异,且已在动物实验中得到验证。本文就SLE患者肠道菌群的变化及其与疾病发生发展的关系进行系统综述,以期为SLE的治疗提供新的思路。

, correspAuthors=张斌, authorNote=null, correspAuthorsNote=
张斌,E-mail:
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郭林峰,硕士研究生,主要从事系统性红斑狼疮与肠道菌群关系方面的研究

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郭林峰,硕士研究生,主要从事系统性红斑狼疮与肠道菌群关系方面的研究

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郭林峰,硕士研究生,主要从事系统性红斑狼疮与肠道菌群关系方面的研究

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SLE. 系统性红斑狼疮;SCFA. 短链脂肪酸;DC. 树突细胞;Treg. 调节性T细胞;Th1. 辅助性T细胞1(CD阳性细胞);Th17. 辅助性T细胞17;IL. 白细胞介素;TNF-α. 肿瘤坏死因子-α;SLE. 系统性红斑狼疮;F/B. 厚壁菌门与拟杆菌门比例;A. 健康人群,肠道屏障完整(厚壁菌门丰度增加、拟杆菌门减少),促炎因子与抗炎因子稳态平衡;B. SLE患者,肠道屏障破坏(F/B降低,特定菌种变化、多样性下降,SCFA减少,促炎因子多于抗炎因子,细菌易位,自身抗体产生,促使免疫失衡,导致机体炎症发生)

, figureFileSmall=+b5LWv391/ed1KNzsJKP7g==, figureFileBig=FEXjwvTg8b4EUcEE4vu4Lw==, tableContent=null), ArticleFig(id=1194634123202499196, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194613945832022189, language=EN, label=Tab.1, caption=

Intestinal differences between SLE patients and healthy populations in different countries

, figureFileSmall=null, figureFileBig=null, tableContent=
国家队列(女:男)结果引用
西班牙20 SLE (20:0) vs. 20 HCs (20:0)↓F/B[35]
中国92 SLE (NI) vs. 217 HCs (NI)↑拟杆菌门、变形菌门、放线菌门、瘤胃球菌门、克雷伯菌属、丹毒科(瘤胃球菌属与外周血中调节性T细胞计数的相关性);↓厚壁菌门、粪杆菌门[43]
荷兰30 SLE (28:2) vs. 965 性别匹配的HCs↓细菌丰富度,F/B;↑拟杆菌门、变形菌门、拟杆菌门、另枝菌属、寻常杆菌、均匀杆菌、卵形双歧杆菌和双歧杆菌[28]
美国61 SLE (61:0) vs. 17 HCs (17:0)↓SLEDAI评分较高患者的细菌丰度;↑瘤胃球菌、毛螺菌科、韦荣球菌科、与疾病活动和狼疮性肾炎相关的抗瘤胃球菌抗体[44]
法国16 SLE vs. 76 HCs↓软壁菌门;↑另枝菌属、荧光杆菌属、丹毒丝菌科、副拟杆菌属[31]
), ArticleFig(id=1194634123298968189, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194613945832022189, language=CN, label=表1, caption=

不同国家SLE患者与健康人群肠道菌群组成的差异

, figureFileSmall=null, figureFileBig=null, tableContent=
国家队列(女:男)结果引用
西班牙20 SLE (20:0) vs. 20 HCs (20:0)↓F/B[35]
中国92 SLE (NI) vs. 217 HCs (NI)↑拟杆菌门、变形菌门、放线菌门、瘤胃球菌门、克雷伯菌属、丹毒科(瘤胃球菌属与外周血中调节性T细胞计数的相关性);↓厚壁菌门、粪杆菌门[43]
荷兰30 SLE (28:2) vs. 965 性别匹配的HCs↓细菌丰富度,F/B;↑拟杆菌门、变形菌门、拟杆菌门、另枝菌属、寻常杆菌、均匀杆菌、卵形双歧杆菌和双歧杆菌[28]
美国61 SLE (61:0) vs. 17 HCs (17:0)↓SLEDAI评分较高患者的细菌丰度;↑瘤胃球菌、毛螺菌科、韦荣球菌科、与疾病活动和狼疮性肾炎相关的抗瘤胃球菌抗体[44]
法国16 SLE vs. 76 HCs↓软壁菌门;↑另枝菌属、荧光杆菌属、丹毒丝菌科、副拟杆菌属[31]
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肠道菌群与系统性红斑狼疮关系的研究进展
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郭林峰 , 张斌 * , 王宏智 , 杨明峰
解放军医学杂志 | 肠道菌群在疾病发生及治疗中的作用专题 2025,50(3): 284-291
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解放军医学杂志 | 肠道菌群在疾病发生及治疗中的作用专题 2025, 50(3): 284-291
肠道菌群与系统性红斑狼疮关系的研究进展
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郭林峰, 张斌* , 王宏智, 杨明峰
作者信息
  • 浙江中医药大学嘉兴大学联合培养基地,浙江杭州 310053
  • 郭林峰,硕士研究生,主要从事系统性红斑狼疮与肠道菌群关系方面的研究

通讯作者:

张斌,E-mail:
Research progress of the relationship between gut microbiota and systemic lupus erythematosus
Lin-Feng Guo, Bin Zhang* , Hong-Zhi Wang, Ming-Feng Yang
Affiliations
  • Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China
出版时间: 2025-03-28 doi: 10.11855/j.issn.0577-7402.0941.2025.0121
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系统性红斑狼疮(SLE)是一种免疫系统异常激活后攻击自身组织导致的慢性弥漫性结缔组织病;其病程复杂,以血管炎为病理基础。近年来,关于SLE与肠道菌群关系的研究明显增多,但具体如何调节肠道菌群以治疗SLE尚未明确。研究发现,SLE患者的肠道菌群与健康人群在厚壁菌门、拟杆菌门、放线菌门、变形菌门等方面存在差异,且已在动物实验中得到验证。本文就SLE患者肠道菌群的变化及其与疾病发生发展的关系进行系统综述,以期为SLE的治疗提供新的思路。

系统性红斑狼疮  /  16S DNA  /  宏基因  /  肠道菌群

Systemic lupus erythematosus (SLE) is a chronic diffuse connective tissue disease characterized by abnormal activation of the immune system, which attacks the body's tissues. It has a complex course and its pathological basis is vasculitis. In recent years, research on the relationship between SLE and the gut microbiota has increased significantly, but how to regulate the gut microbiota for the treatment of SLE remains unclear. Studies have found that the intestinal microbiota of SLE patients differs from that of healthy people in terms of Firmicutes, Bacteroidetes, Actinomycetes, and Proteobacteria, etc., and this has been verified in animal experiments. In this review, the changes of intestinal microbiota in SLE patients and their association with the pathogenesis and progression of the disease are systematically reviewed, aiming to provide new insights into the treatment of SLE.

systemic lupus erythematosus  /  16S DNA  /  metagene  /  intestinal flora
郭林峰, 张斌, 王宏智, 杨明峰. 肠道菌群与系统性红斑狼疮关系的研究进展. 解放军医学杂志, 2025 , 50 (3) : 284 -291 . DOI: 10.11855/j.issn.0577-7402.0941.2025.0121
Lin-Feng Guo, Bin Zhang, Hong-Zhi Wang, Ming-Feng Yang. Research progress of the relationship between gut microbiota and systemic lupus erythematosus[J]. Medical Journal of Chinese People’s Liberation Army, 2025 , 50 (3) : 284 -291 . DOI: 10.11855/j.issn.0577-7402.0941.2025.0121
系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种系统性自身免疫性疾病[1],临床表现为疲劳、关节炎、皮疹及严重的器官损害等,显著降低了患者的生活质量并增加了死亡风险[2]。SLE的病因及发病机制尚不明确,研究表明,遗传、环境因素和免疫系统异常调控在其病理过程中起着重要作用[1,3-7];随着皮质类固醇、免疫抑制剂及生物制剂的应用[8-9],SLE的病死率明显降低[10],但仍不能完全满足临床需求[11]。近年来有关肠道菌群与自身免疫关系的研究逐渐增多,SLE患者与健康人群的菌群差异也得到了广泛验证;肠道菌群与SLE疾病活动之间存在一定联系,参与了SLE的发生发展。为此,本文综述了肠道菌群与SLE之间的复杂关系,探讨如何通过调节肠道菌群来制定新的治疗策略,并分析了肠道菌群对SLE免疫路径的影响,以期为临床上实现精准医疗提供帮助。
肠道菌群是人体肠道的正常微生物,包括有益菌、有害菌和中性菌。肠道菌群与人类宿主是一个处于动态变化并维持平衡的生态系统,需要宿主免疫系统与共生菌群之间相互作用来维持稳定,以保证宿主健康[12-18]。人体肠道内有数以亿计的微生物[19-20],它们是内外环境的监察者,其定植状态受宿主遗传、疾病状态、免疫健康、饮食、社会经济状况、药物和地域等因素的影响[21-22]。随着年龄增长及人体的衰老,肠道菌群的丰富性降低[23-24],而菌群结构改变可能是诱发疾病的关键因素之一[25]。一些共生物种产生的短链脂肪酸(short chain fatty acid,SCFA)丁酸盐可促进T细胞分化为调节性T细胞(regulatory T cells,Tregs),影响肠道上皮细胞,从而增强肠道屏障功能,而在肠道菌群结构异常和病原体有限感染的恶性循环下,机体免疫系统通过促炎因子释放、辅助性T细胞激活、表位扩散和分子模拟、细菌抗原易位,最终使肠道屏障完整性被破坏,而肠道屏障功能缺陷可导致共生致病性细菌DNA和(或)其释放的促炎产物(如内毒素和脂肽)易位,进入外周淋巴组织、肝和其他部位,造成局部组织损伤。此外,微生物可影响自我反应性淋巴细胞的耐受性,导致表位扩散,对自身抗原的免疫反应,以及炎症反应诱导的旁路激活,从而降低淋巴细胞激活阈值或使辅助性T细胞异常,导致免疫调节受损[26]。但目前对于菌群差异的了解仍非常有限,特定菌群对免疫的影响亟待进一步研究[16]。肠道菌群与宿主的相互作用对维持免疫平衡、代谢健康及防御病原体入侵至关重要[27]。研究表明,肠道微生物失衡与肥胖症、糖尿病、心血管疾病及多种自身免疫疾病的发生发展密切相关[1,3,28-34]
随着二代测序(next generation sequencing,NGS)技术的发展,越来越多的证据表明肠道菌群在SLE的发病机制中起着关键作用[7]。通过现代分子生物学技术如16S rRNA基因测序和宏基因组学分析发现,SLE患者的肠道菌群组成与健康人群存在显著差异[35],主要表现为某些促炎菌群的丰度增加以及有益菌群的丰度降低,这些菌群可能通过影响宿主免疫反应促进SLE的病理进程。虽然16S rRNA扩增子分析仍是微生物多样性分析的标准方法[36],但相较于宏基因组测序,该技术在微生物的相互作用和功能分析方面存在一定的限制[37]。宏基因组学研究主要集中于对核抗原免疫反应过程的测定,揭示了许多与SLE有关的基因,包括CD11抗原样家族成员B(也被称为整合素αM,ITGAM)、IgG Fc受体、补体成分、C反应蛋白(C-reactive protein,CRP)等[38]。为全面理解肠道菌群与SLE的关系,笔者在PubMed、Web of Science和Scopus数据库中检索“系统性红斑狼疮”“肠道菌群”“16S rRNA测序”和“宏基因组学”等关键词,收集整理关于肠道菌群对SLE影响的基础和临床研究,以深入理解SLE的病理生理机制,开辟治疗这一复杂疾病的潜在新途径[12,32,39-40]
研究发现,与健康对照组相比,SLE患者的肠道菌群多样性明显降低(P<0.001)[41],表明SLE患者肠道环境的复杂性和稳定性发生改变,可能导致免疫系统功能进一步紊乱。
SLE患者特定的促炎菌群如变形菌门(Proteobacteria)和拟杆菌门(Bacteroidetes)的相对丰度明显增加,而与肠道健康相关的厚壁菌门(Firmicutes)的丰度明显降低[35,42],且以上变化与疾病活动度[如系统性红斑狼疮疾病活动指数(SLEDAI评分)]呈正相关,提示上述菌群在SLE的免疫调节中起着重要作用。由此推测,SLE患者某些促炎菌群的丰度明显增加,而有益菌群的丰度明显降低。表1[28,31,35,43-44]总结了SLE患者与健康人群肠道菌群组成的差异。
SLE患者与健康人群厚壁菌门与拟杆菌门比例(F/B)的变化在不同研究中有所不同,如Hevia等[37]发现,与健康人群比较,SLE患者的F/B降低,而随后其他研究也证实了该结果[29,45-47],但在Rojo等[48]的研究中SLE患者的F/B升高,与之相悖。此外,Tomofuji等[41]通过鸟枪法测序发现SLE宏基因组中A族链球菌和中间链球菌的丰度增加。有研究发现,SLE患者肠道菌群中红球菌属、爱格菌属、克雷伯菌属、普雷沃菌属、真杆菌属、优杆菌属、解黄酮菌属和双丝孢菌属显著富集,而戴阿利斯特杆菌属和假小链双歧杆菌属耗尽[45]。一项综合调查归纳了SLE患者肠道菌群的变化趋势,即乳酸菌属、链球菌属、巨球菌属、梭杆菌属、韦荣菌属、原杆菌属、臭杆菌属、经黏液真杆菌属和弯曲杆菌属明显增加[49]。除了常见的肠道轴,口腔微生物群的菌种在SLE患者肠道中富集[34],但关于口腔-肠道轴微生物的研究鲜见。Li等[50]发现,SLE患者的肠道变形杆菌以鞘单胞菌属为主要菌属,且代谢途径与健康组存在明显差异,表明SLE患者的口腔菌属易位至了肠道轴中。
有研究显示,拟杆菌门和变形菌门丰度与血清中炎症标志物(如CRP、IL-6)及自身抗体(如抗dsDNA抗体)的水平呈正相关,且SLE疾病活动度与肠道菌群存在关联[44,51],因此肠道菌群的变化可能直接影响SLE的免疫病理过程。在健康共生条件下,肠道屏障完好无损,保持多样化和平衡性。SCFA保障了免疫细胞(T、B细胞)的正常分化,平衡辅助性T细胞(Th)1/Th17,并调节Tregs,产生抗炎细胞因子,从而实现免疫自我耐受[52](图1)。
研究发现,SLE患者肠道内瘤胃球菌的比例与Tregs数量呈正相关,但与Th1、Th2和Th17无关[53],提示瘤胃球菌可能通过激活T细胞免疫系统而导致炎性因子的产生,肠道菌群的变化可能通过多种机制影响宿主的免疫系统,包括通过改变肠道屏障功能影响系统性免疫反应。细菌丰度增加(如瘤胃球菌[44])可导致炎性因子释放,从而加重全身炎症。细菌通过自身反应性T、B细胞易位到固有腔中,激活Toll样通路,促进炎性细胞因子、Ⅰ型干扰素(typeⅠinterferon,IFN-Ⅰ)和自身抗体的产生,循环中的炎症产物反复刺激致使耐受性丧失和器官损伤[19]。研究发现,拟杆菌门和变形菌门丰度增加可能促进肠黏膜的渗透性增高,从而允许更多的病原体和内毒素进入血流,触发免疫系统的过度激活[31]
通过调节肠道菌群抑制IFN的表达,治疗SLE患者炎症状态的效果尚不明确。现有研究表明,肠道微生态可能作用于不同的免疫通路,导致免疫激活或免疫抑制,而从肠道微生态角度探索SLE的发病机制仍存在一些限制,如样本量较小等[31]。未来应设计前瞻性队列研究,并纳入多中心样本进行深入探讨。此外,通过宏基因组测序技术探索特定微生物的代谢产物及其与宿主免疫系统的直接相互作用,可能是理解肠道微生物对SLE影响的关键。
NGS测序发现,SLE患者和动物模型中F/B均有所下降[22,54],值得注意的是,不同的狼疮鼠模型中的乳酸杆菌相对丰度呈现不同的变化。MRL/lpr小鼠中乳酸杆菌科的比例降低[55-56],而毛螺菌科富集[57];NZB/WF1小鼠中乳酸菌的相对丰度随着SLE病情的进展而增加,而地塞米松治疗后乳酸杆菌减少[55]。TLR7.1 Tg小鼠中罗伊氏乳杆菌、理研菌科和脱硫弧菌属富集[58],其中罗伊氏乳杆菌可破坏肠道上皮通透性,增加IFN-Ⅰ的表达,加重消化道炎症,进而加剧SLE病情[55]。IFN-α在TLR7.1 Tg小鼠中起主要作用,而在MRL/lpr小鼠中IFN-γ起主要作用[59]。在F1小鼠(NZW×BXSB)中,肠道共生大肠埃希菌向肝易位可触发IFN-Ⅰ的表达和抗dsDNA抗体的产生[60],表明肠道菌群在SLE病理进程中具有重要作用。研究发现,拟杆菌门、变形菌门丰度增加以及厚壁菌门减少与SLE疾病活动度相关[31,44],肠道菌群的变化可能通过影响宿主免疫调节路径(如炎症信号转导和自身抗体生成)而发挥作用。NZB/WF1鼠中梭状芽孢杆菌、脱盐杆菌、乳酸杆菌、颤螺菌属、多尔氏菌、嗜胆菌属、AF12属和反刍球菌科中一个未命名属的丰度随SLE病情进展而增加[56]。Johnson等[61]对SNF1小鼠给予酸性水或中性水喂养,通过16S RNA基因靶向测序发现,两组小鼠的肠道微生物组成存在差异,且酸性水组小鼠肾炎进展较中性水组延缓。由于两组小鼠饮食中仅改变了水的酸碱度,因此推测肠道菌群可能是影响肾炎进展的唯一因素。而肾炎的进展与免疫系统紊乱相关,其机制为促进各种炎性介质的产生,加速肾炎进展,两者似乎具有“因果”的纽带关系。Chen等[18]发现,肠道共生菌定植可增加B细胞库中的抗菌特异性反应细胞,还可引发及增强反应性IgA和IgG反应;SLE患者最显著的特点是形成一系列自身抗体的多反应性B细胞,包括抗dsDNA、抗核糖核蛋白(RNP)、抗Ro、抗La、抗磷脂以及抗核抗原抗体[62],肠道共生定植菌与SLE的多反应性B细胞产生的自身抗体可能存在一定联系。未来的研究可在不同狼疮小鼠模型中验证共生菌群的差异及其与已知的免疫通路反应之间的关系,以确定SLE可能的发病机制。
目前SLE主要采用激素(如醋酸泼尼松或甲泼尼龙)、免疫抑制剂、生物制剂等治疗,以长期维持完全缓解或低疾病活动度状态[32,63-64],但不良反应较多。一项研究收集了20名健康者(HC组;SLEDAI评分0分)、17例未接受激素治疗的SLE患者(SLE-G组;SLEDAI评分0~12分)和20例接受激素治疗的SLE患者(SLE+G组;SLEDAI评分1~14分),其中SLE+G组患者肠道微生物群落多样性和结构发生显著变化,肠道细菌多样性降低,但肠道微生物群落仍与HC组相似;SLE-G组患者肠道中富集了拟杆菌和双岐杆菌,且在门和属水平上细菌数量均有所增加[29]。研究发现,激素治疗可增加感染、骨质疏松和心血管事件的发生风险[65]。越来越多的证据表明,肠道菌群对SLE存在一定影响[66-67],可通过肠道微生物作用刺激多种炎性细胞因子的产生和炎性细胞的形成[68-69]。研究人员正尝试从肠道菌群与SLE发病机制相关联的角度,探寻治疗免疫介导疾病的新方向[3,12-13,15],并构建肠道-微生物-代谢产物-机体免疫轴的新治疗渠道,因此肠道菌群可能成为评估SLE预后的新生物靶点。
环境因素包括微生物和饮食,在启动遗传易感个体的自身免疫中起着关键作用[61]。细菌代谢物对膳食中碳水化合物、脂肪、蛋白质和维生素的代谢途径均具有明显影响,而SLE患者新陈代谢存在明显异常[70]。多种细菌、平衡的共生体和病原体、生物体共同组成健康的肠道菌群,而致病菌的长期存在通常不引起炎症,只有在特定环境下才可能引发炎症并诱发疾病。微生物群落组成无论是病原微生物的增加还是共生体的减少,均可造成微生物群落失调,干扰宿主免疫功能的调节[25,71]。在自发性免疫疾病中,有研究者提出地中海饮食可适用于类风湿关节炎(rheumatoid arthritis,RA)的治疗,富含omega-3多不饱和脂肪酸(ω‑3 polyunsaturated fatty acids,ω-3 PUFAs)、多酚和膳食纤维的饮食可调控Tregs的分化,减轻全身炎症反应,调节肠道菌群,改善肠道屏障功能,从而改善RA患者的预后[72]
现有证据表明,SCFA在宿主健康和疾病中扮演着重要角色[73-75]。其中,ω-3 PUFAs已被用于治疗SLE,在降低心血管疾病风险[76],降低CRP、抗dsDNA滴度、IL-1和IL-12水平[77],调节肿瘤坏死因子(tumor necrosis factor,TNF)水平[78],以及调控蛋白尿、血尿和血压[79]方面具有显著效果。一项采用罗伊氏乳杆菌抗性淀粉进行饮食干预的研究发现,促进肠道菌群将纤维发酵成SCFA可降低罗伊氏乳杆菌的丰度,下调IFN-Ⅰ的表达,改善狼疮样表现。此外,高色氨酸饮食可加重狼疮的进展[80],而这与普氏菌群的改变有关;SNF1小鼠给予酸性水喂养可延缓肾炎的进展,而补充视黄酸可调节MRL/lpr小鼠的乳酸菌丰度,缓解狼疮症状[57]。口服醋酸拉拉唑肽(一种八肽)可有效逆转瘤胃球菌所导致的肠漏,减轻炎症[51]。SLE模型小鼠摄入定量的膳食纤维有助于恢复功能失调的肠道-免疫系统-血管壁轴平衡,保护血管及肾脏[81-82]。而SLE患者限制热量和摄入适量蛋白质有利于增强机体免疫功能,抑制SLE的进展,并降低疲劳度[83]。另有研究表明,一种间歇性禁食的饮食结构可能有益于提高自身免疫功能,可减少炎症标志物,改善肠道菌群稳态,并通过自噬增强细胞修复机制[84]。饮食疗法确实是一种可行的方法,但个体化治疗方案的制订困难,长期坚持定时定量服用较难实现,且效果不如药物见效快,长期效果仍需更多临床案例的支持。
相较RA、多发性硬化症和强直性脊柱炎[85]等其他自身免疫疾病,SLE的肠道菌群变化具有一定独特性,但也存在一些共通的病理特征,如促炎菌群增加和有益菌群减少[86]。乳酸菌和双歧杆菌属被认为是SCFA的生产者,可增强肠道屏障功能。有研究发现,连续服用8周益生菌或干酪等可降低RA的活动度[86-87],类似研究在SLE中也取得了相同的结果[88]。MRL/lpr小鼠注射热杀灭干酪乳杆菌可加速巨噬细胞募集并防止B220+ T细胞扩增,且不影响B220+ T细胞的功能[89]。在SLE模型中,乳酸菌作为益生菌可减少白细胞介素(interleukin,IL)-6的产生及促进IL-10的分泌,发挥免疫调节和抗炎作用[56]。狼疮易感小鼠(NZBxNZW)F1 (BWF1)进食干酪乳杆菌或罗伊氏乳杆菌可有效延缓肾炎进展并提高生存率[90]。长期使用益生菌能改善肠道微生态,调节自身抗体,缓解SLE症状[91]。而Zegarra-Ruiz等[58]的研究结果却截然相反:罗伊氏乳杆菌可加剧Toll样受体7(TLR-7)依赖性小鼠模型的疾病进展。有研究表明,合生元治疗后,SLE肠道菌群中致病菌普雷沃菌和拟杆菌门的相对丰度降低,而放线菌门和厚壁菌门的丰度增加;生物丰度和多样性分析发现,氨基酸的生物合成、氨酰基-tRNA的生物合成、嘌呤代谢等代谢途径与合生元治疗关系密切[92]
FMT是将健康人粪便中的功能菌群移植到患者胃肠道内,使其定植生长,在一定周期内重新构建患者的肠道微生态,以实现肠道及肠道外疾病的治疗。目前FMT已被尝试应用于肝病的治疗中[93]。在SNF1小鼠模型中,早期进行FMT可有效抑制SLE的发展[43,61,94]。然而,FMT存在感染的风险,仍需考量其可行性。有研究纳入14例SLE患者并给予FMT治疗,应用宏基因测序发现肠道菌群可通过SCFA诱导DNA甲基化,由此提出了FMT可能通过恢复异常低甲基化水平实现治疗目的[95-96]。在近期一项为期12周的临床试验中,20例活动性SLE患者首次口服FMT胶囊,治疗后患者SCFA富集,炎症相关细菌类群减少,肠道微生物群落从促炎状态转变为非炎症状态,SLE反应指数-4(SRI-4)、抗dsDNA抗体滴度明显降低,SLEDAI评分明显改善[96]
结合肠道菌群的调节潜力,未来的治疗策略可能包括使用针对性的益生菌或益生元来恢复肠道菌群平衡,或通过FMT来重建健康的肠道微环境。这些干预措施在提高SLE患者生活质量和疾病管理方面具有重要的潜在价值。
SLE主要影响育龄期女性,且主要受遗传、激素(人体自身产生)和环境因素的影响[97]。大量研究证实,人体胃肠道中定植着数以亿计的肠道微生物,对宿主免疫系统具有重要的调节作用,其中肠道菌群占主导地位。而肠道菌群失调是SLE发病的原因之一,肠道菌群与SLE症状严重程度之间的关联强化了微生物-宿主在自身免疫疾病中的理论模型,肠道菌群可能通过调节宿主的炎症反应途径如核因子κB(NF-κB)信号通路影响炎性细胞因子的表达,在SLE的发病中发挥作用。此外,肠道菌群可通过分泌调节免疫功能的SCFA如丁酸来干预T细胞的分化和功能,这为开发新的治疗策略提供了分子层面的依据。肠道菌群的调节策略在SLE的治疗中具有重要的潜在应用价值,相较传统的免疫抑制治疗方法更为安全和自然[98]。进一步的研究应关注如何将这些实验室发现转化为临床应用,如通过临床试验检测特定的益生菌或益生菌配方对SLE患者的影响。虽然当前的研究为肠道菌群在SLE中的作用提供了初步证据,但未来的研究需要解决以下关键问题:(1)精确鉴定和定量与SLE病理过程直接相关的微生物;(2)在不影响肠道菌群整体平衡的前提下有效调节这些关键菌群;(3)评估长期调节肠道菌群对SLE患者健康的影响。
  • 嘉兴市科技计划项目(2021AD30174)
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2025年第50卷第3期
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doi: 10.11855/j.issn.0577-7402.0941.2025.0121
  • 接收时间:2024-06-27
  • 首发时间:2025-11-10
  • 出版时间:2025-03-28
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  • 收稿日期:2024-06-27
  • 录用日期:2024-08-04
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嘉兴市科技计划项目(2021AD30174)
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    浙江中医药大学嘉兴大学联合培养基地,浙江杭州 310053

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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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