人体通常能与消化道中上千万的细菌和睦共处，如果没有它们，人体的健康也会受到影响。实际上，共生微生物群中的不平衡被认为对于炎症性肠病的发病起到了促进作用。如今，发表在《自然》上的一项研究表明，由脆弱拟杆菌(Bacteroides fragilis)——一种常见的哺乳动物共生细菌——产生的一种因子能够防止小鼠的肠道炎症。
在这项研究中，美国加利福尼亚理工学院的Sarkis K. Mazmanian和同事首先使用了一种实验用大肠炎的有效模型，它将致病T细胞转移到特殊的没有病菌的免疫缺陷小鼠体内。随着细胞转移，小鼠被移植了肝螺杆菌(Helicobacter hepaticus)，后者能够在免疫缺陷动物体内导致严重的大肠炎。然而，同时移植脆弱拟杆菌却能保护小鼠远离疾病；这些小鼠的肠道组织并没有表现出炎症前期细胞因子肿瘤坏死因子（TNF）、白细胞介素1β(IL-1β)和IL-12p40水平的增加，同时动物的体重也没有下降。然而如果小鼠接受了脆弱拟杆菌的一种变异菌株——缺乏制造酯化多糖A(PSA)的能力，则不会产生这种保护作用，这表明这种微生物因子在大肠炎的抑制中扮演了一个角色。
PSA的有益功效随后在另一项实验中得到了证实——口服纯净PSA几乎足以保护小鼠完全避免由T细胞转移和肝螺杆菌移植导致的大肠炎。在对第二种大肠炎实验模型进行的研究中，通过直肠使用三硝基苯磺酸的诱导，同样支持PSA的保护功效。在这种模型中，口服PSA防止了导致疾病的T辅助细胞的感应，以及TNF产量的提高。
接下来，科学家研究了PSA防止大肠炎的机制。他们发现，从用PSA治疗的小鼠的肠系膜淋巴结净化的CD4+T细胞包含有更高水平的编码抗炎症细胞因子IL-10的mRNA。与IL-10在调节PSA的保护功能中扮演的角色一致，IL-10特定受体抗体在口服PSA治疗期间的使用，抑制了对大肠炎的保护。最终，由转移T细胞导致的IL-10的产出被证明是这种保护所必需的。
研究人员认为，这些结果表明，来自所谓友好细菌的因子在维持人体与共生细菌之间的和睦关系时具有至关重要的作用。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 453, 620-625 (29 May 2008) | doi:10.1038/nature07008
A microbial symbiosis factor prevents intestinal inflammatory disease
Sarkis K. Mazmanian1,4, June L. Round1,4 & Dennis L. Kasper2,3
1 Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
2 Channing Laboratory, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
3 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
4 These authors contributed equally to this work.
Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.
