The microbiota and inflammatory bowel disease: insights from animal models.
The microbiota and inflammatory bowel disease: insights from animal models.
复制标题
DOI：
10.1016/j.anaerobe.2013.04.006
复制
发表时间：
2013-12
期刊：
影响因子：
2.3
通讯作者：
Nguyen, Deanna D.
中科院分区：
文献类型：
--
作者：
Peloquin, Joanna M.;Nguyen, Deanna D.
炎症性肠病（IBD）被认为是由具有遗传易感性的个体对肠道微生物菌群的免疫反应失调引起的。人类IBD的全基因组关联研究（GWAS）已经确定了150多个相关位点，其中一些在先天免疫和细菌处理中起关键作用，反映了微生物群在疾病发病机制中的重要性。事实上，微生物菌群的存在不仅对正常小鼠免疫系统的发育至关重要，而且对大多数IBD动物模型的疾病发展也至关重要。尽管动物模型不能完美地概括人类IBD，但它们已经导致IBD发病机制中重要概念的发现，例如微生物群在疾病发展和延续中的核心作用。许多遗传易感模型在无菌或无幽门螺杆菌的环境中饲养时不会发生结肠炎。事实上，在大多数模型中，疾病可以通过抗生素治疗减弱或完全消除。此外，在某些自发性结肠炎模型和人类患者中，存在针对Cbir1鞭毛蛋白（一种激活TLR5的免疫优势抗原）的血清抗体，表明肠道微生物群与粘膜免疫激活之间存在相互作用。此外，对Cbir1反应的T细胞在过继细胞转移后能够在受体小鼠中诱导疾病，这表明某些细菌产物具有促炎特性。事实上，有研究表明，从具有自发性结肠炎的特定转基因小鼠模型中转移某些肠道细菌，可以在野生型小鼠共住或直接喂养时诱导疾病。这些观察结果证明了肠道微生物群在IBD中的致病潜力。然而，肠道细菌并不总是不适应粘膜稳态。脆弱拟杆菌和梭状芽孢杆菌都能促进结肠中某种调节性T细胞亚群的数量和功能，从而预防小鼠结肠炎。事实上，在缺乏肠道菌群的情况下，调节细胞的正常发育和上皮细胞的完整性被破坏，这表明需要某些微生物成分来诱导有益的抗炎机制。总而言之，对微生物的免疫反应改变在IBD发病机制中起着至关重要的作用。然而，微生物群的某些组成部分也可能对促进粘膜稳态的调节机制的正常发育至关重要。动物模型的发现强调了IBD是一种由遗传和微生物/环境因素相互作用导致的疾病。
Inflammatory bowel disease (IBD) is thought to result from a dysregulated immune response to intestinal microbial flora in individuals with genetic predisposition(s). Genome wide association studies (GWAS) in human IBD have identified more than 150 associated loci, some of which are key players in innate immunity and bacterial handling, reflecting the importance of the microbiota in disease pathogenesis. In fact, the presence of a microbial flora is not only crucial to the development of a normal murine immune system but also critical for the development of disease in the majority of animal models of IBD. Although animal models do not perfectly recapitulate human IBD, they have led to the discovery of important concepts in IBD pathogenesis, such as the central role of microbiota in disease development and perpetuation. Many genetically susceptible models do not develop colitis when raised in a germ-free or Helicobacter-free environment. In fact, disease in most models can be attenuated or completely abolished with antibiotic treatment. Moreover, an interplay between intestinal microbiota and mucosal immune activation is suggested by the presence of serum antibodies against the Cbir1 flagellin, an immunodominant antigen that activates TLR5, in certain models of spontaneous colitis as well as in human patients. Furthermore, T cells reactive to Cbir1 are able to induce disease in recipient mice upon adoptive cell transfer, demonstrating the pro-inflammatory properties of certain bacterial products. In fact, it has been shown that transfer of certain intestinal bacteria from a specific genetically altered mouse model with spontaneous colitis can induce disease in wild-type mice upon co-housing or direct feeding. These observations demonstrate the pathogenic potential of intestinal microbiota in IBD. However, intestinal bacteria are not always maladaptive in mucosal homeostasis. Both Bacteroides fragilis and Clostridium species promote the number and function of a certain regulatory T cell subset in the colon leading to protection against murine colitis. In fact, normal development of regulatory cells and epithelial cell integrity are abolished in the absence of an intestinal flora, suggestive of the need for certain microbial components to induce beneficial anti-inflammatory mechanisms. All in all, altered immune responses to microbes play a crucial role in IBD pathogenesis. However, certain components of the microbiota are also likely critical for normal development of regulatory mechanisms that contribute to mucosal homeostasis. Findings in animal models highlight the concept that IBD is a disease that results from the interplay of genetics and microbial/environmental factors.
登录
查看更多内容
影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
15.8
作者：
Kang, Silvia S.;Bloom, Seth M.;Norian, Lyse A.;Geske, Michael J.;Flavell, Richard A.;Stappenbeck, Thaddeus S.;Allen, Paul M.
通讯作者：
Allen, Paul M.
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
64.8
作者：
Khor, Bernard;Gardet, Agnes;Xavier, Ramnik J.
通讯作者：
Xavier, Ramnik J.
影响因子：
17.1
作者：
Blumberg R;Powrie F
通讯作者：
Powrie F