Modulation of Mucosal Immune Response, Tolerance, and Proliferation in Mice Colonized by the Mucin-Degrader Akkermansia muciniphila.
Modulation of Mucosal Immune Response, Tolerance, and Proliferation in Mice Colonized by the Mucin-Degrader Akkermansia muciniphila.
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DOI：
10.3389/fmicb.2011.00166
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发表时间：
2011
影响因子：
5.2
通讯作者：
de Vos WM
中科院分区：
文献类型：
--
作者：
Derrien M;Van Baarlen P;Hooiveld G;Norin E;Müller M;de Vos WM
哺乳动物肠的上皮细胞覆盖有粘液层，该粘液层防止与肠微生物直接接触，但也构成粘液降解细菌的基质。为了研究粘液降解对宿主应答的影响，用嗜粘蛋白阿克曼氏菌定殖无菌小鼠。这种属于疣微菌属的厌氧细菌专门降解粘蛋白，粘蛋白是粘液中存在的糖蛋白，并且在人类和其他哺乳动物物种的肠道中大量发现。A.在产生大多数粘蛋白的盲肠中观察到数量最多的嗜粘蛋白菌。相比之下，植物乳杆菌（一种属于厚壁菌门的兼性厌氧菌，可发酵碳水化合物）定植后，在所有肠道部位发现了相似的细胞数量。而A.嗜粘蛋白L. plantarum仅在管腔中发现。在肠道活组织检查中确定了总体转录宿主反应，并揭示了在被A. muciniphila和超过1500个基因的克隆。植物途径重建表明，A.嗜粘蛋白菌改变了粘膜基因表达谱，使参与免疫应答和细胞命运决定的基因表达增加，而嗜粘蛋白菌定植于粘膜。plantarum导致脂质代谢上调。这些表明，定殖诱导宿主的反应是特定的每个肠道位置。最后，我们提出了A.嗜粘蛋白调节参与建立基础代谢的稳态和对肠道微生物群的免疫耐受的途径。
Epithelial cells of the mammalian intestine are covered with a mucus layer that prevents direct contact with intestinal microbes but also constitutes a substrate for mucus-degrading bacteria. To study the effect of mucus degradation on the host response, germ-free mice were colonized with Akkermansia muciniphila. This anaerobic bacterium belonging to the Verrucomicrobia is specialized in the degradation of mucin, the glycoprotein present in mucus, and found in high numbers in the intestinal tract of human and other mammalian species. Efficient colonization of A. muciniphila was observed with highest numbers in the cecum, where most mucin is produced. In contrast, following colonization by Lactobacillus plantarum, a facultative anaerobe belonging to the Firmicutes that ferments carbohydrates, similar cell-numbers were found at all intestinal sites. Whereas A. muciniphila was located closely associated with the intestinal cells, L. plantarum was exclusively found in the lumen. The global transcriptional host response was determined in intestinal biopsies and revealed a consistent, site-specific, and unique modulation of about 750 genes in mice colonized by A. muciniphila and over 1500 genes after colonization by L. plantarum. Pathway reconstructions showed that colonization by A. muciniphila altered mucosal gene expression profiles toward increased expression of genes involved in immune responses and cell fate determination, while colonization by L. plantarum led to up-regulation of lipid metabolism. These indicate that the colonizers induce host responses that are specific per intestinal location. In conclusion, we propose that A. muciniphila modulates pathways involved in establishing homeostasis for basal metabolism and immune tolerance toward commensal microbiota.
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影响因子：
4.9
作者：
Lepage, P;Seksik, P;Doré, J
通讯作者：
Doré, J
DOI：
10.1073/pnas.0504978102
发表时间：
2005-08-02
影响因子：
11.1
作者：
Ley, RE;Bäckhed, F;Gordon, JI
通讯作者：
Gordon, JI
影响因子：
4.4
作者：
Collado, M. Carmen;Derrien, Muriel;Isolauri, Erika
通讯作者：
Isolauri, Erika
影响因子：
4.4
作者：
Favier, CF;Vaughan, EE;Akkermans, ADL
通讯作者：
Akkermans, ADL
DOI：
10.1073/pnas.0810305105
发表时间：
2008-12-09
影响因子：
11.1
作者：
Konstantinov, Sergey R.;Smidt, Hauke;van Kooyk, Yvette
通讯作者：
van Kooyk, Yvette