人體通常能與消化道中上千萬的細(xì)菌和睦共處,，如果沒有它們,，人體的健康也會受到影響,。實際上,，共生微生物群中的不平衡被認(rèn)為對于炎癥性腸病的發(fā)病起到了促進(jìn)作用,。如今，發(fā)表在《自然》上的一項研究表明,，由脆弱擬桿菌(Bacteroides fragilis)——一種常見的哺乳動物共生細(xì)菌——產(chǎn)生的一種因子能夠防止小鼠的腸道炎癥,。
在這項研究中,，美國加利福尼亞理工學(xué)院的Sarkis K. Mazmanian和同事首先使用了一種實驗用大腸炎的有效模型，它將致病T細(xì)胞轉(zhuǎn)移到特殊的沒有病菌的免疫缺陷小鼠體內(nèi),。隨著細(xì)胞轉(zhuǎn)移,，小鼠被移植了肝螺桿菌(Helicobacter hepaticus)，后者能夠在免疫缺陷動物體內(nèi)導(dǎo)致嚴(yán)重的大腸炎,。然而,，同時移植脆弱擬桿菌卻能保護(hù)小鼠遠(yuǎn)離疾病,；這些小鼠的腸道組織并沒有表現(xiàn)出炎癥前期細(xì)胞因子腫瘤壞死因子（TNF）,、白細(xì)胞介素1β(IL-1β)和IL-12p40水平的增加，同時動物的體重也沒有下降,。然而如果小鼠接受了脆弱擬桿菌的一種變異菌株——缺乏制造酯化多糖A(PSA)的能力,，則不會產(chǎn)生這種保護(hù)作用，這表明這種微生物因子在大腸炎的抑制中扮演了一個角色,。
PSA的有益功效隨后在另一項實驗中得到了證實——口服純凈PSA幾乎足以保護(hù)小鼠完全避免由T細(xì)胞轉(zhuǎn)移和肝螺桿菌移植導(dǎo)致的大腸炎,。在對第二種大腸炎實驗?zāi)Ｐ瓦M(jìn)行的研究中，通過直腸使用三硝基苯磺酸的誘導(dǎo),，同樣支持PSA的保護(hù)功效,。在這種模型中，口服PSA防止了導(dǎo)致疾病的T輔助細(xì)胞的感應(yīng),，以及TNF產(chǎn)量的提高,。
接下來，科學(xué)家研究了PSA防止大腸炎的機(jī)制,。他們發(fā)現(xiàn),，從用PSA治療的小鼠的腸系膜淋巴結(jié)凈化的CD4+T細(xì)胞包含有更高水平的編碼抗炎癥細(xì)胞因子IL-10的mRNA。與IL-10在調(diào)節(jié)PSA的保護(hù)功能中扮演的角色一致,，IL-10特定受體抗體在口服PSA治療期間的使用,，抑制了對大腸炎的保護(hù)。最終,，由轉(zhuǎn)移T細(xì)胞導(dǎo)致的IL-10的產(chǎn)出被證明是這種保護(hù)所必需的。
研究人員認(rèn)為,，這些結(jié)果表明,，來自所謂友好細(xì)菌的因子在維持人體與共生細(xì)菌之間的和睦關(guān)系時具有至關(guān)重要的作用。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
