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黏液层内的黏度梯度决定了黏膜屏障功能以及肠道微生物群的空间组织。

Viscosity gradient within the mucus layer determines the mucosal barrier function and the spatial organization of the intestinal microbiota.

作者信息

Swidsinski Alexander, Sydora Beate C, Doerffel Yvonne, Loening-Baucke Vera, Vaneechoutte Mario, Lupicki Maryla, Scholze Juergen, Lochs Herbert, Dieleman Levinus A

机构信息

Humboldt University, Charité Hospital, CCM, Laboratory for Molecular Genetics, Polymicrobial Infections and Bacterial Biofilms, Berlin, Germany.

出版信息

Inflamm Bowel Dis. 2007 Aug;13(8):963-70. doi: 10.1002/ibd.20163.

DOI:10.1002/ibd.20163
PMID:17455202
Abstract

BACKGROUND

Migration is an important virulence factor for intestinal bacteria. However, the role of bacterial mobility in the penetration of viscous mucus and their spatial organization within the colon is relatively unknown.

METHODS

Movements of fecal bacteria were assessed in gels of varying agarose concentrations and were compared with patterns of bacterial distribution observed in colons from conventional and Enterobacter cloacae-monoassociated mice. Bacteria were visualized using fluorescence in situ hybridization.

RESULTS

Long curly bacteria moved best in moderate viscosity gels, short rods and cocci preferred a low viscous environment, whereas high viscosity immobilized all bacterial groups. The spatial distribution of bacteria in the murine colon was also shape- and not taxonomy-dependent, indicating the existence of vertical (surface to lumen) and longitudinal (proximal to distal colon) viscosity gradients within the mucus layer. Our results suggest that mucus viscosity is low in goblet cells, at the crypt basis and close to the intestinal lumen, whereas sites adjacent to the columnar epithelium have a high mucus viscosity. The mucus viscosity increased progressively toward the distal colon, separating bacteria selectively in the proximal colon and completely in the distal colon.

CONCLUSIONS

The site-specific regulation of mucus secretion and dehydration make the mucus layer firm and impenetrable for bacteria in regions close to the intestinal mucosa but loose and lubricating in regions adjacent to the luminal contents. Selective control of mucus secretion and dehydration may prove to be a key factor in the management of chronic diseases in which intestinal pathogens are involved.

摘要

背景

迁移是肠道细菌的一种重要毒力因子。然而,细菌运动性在粘性黏液穿透及在结肠内的空间组织方面所起的作用相对尚不明确。

方法

在不同琼脂糖浓度的凝胶中评估粪便细菌的运动,并与在常规小鼠和阴沟肠杆菌单联小鼠结肠中观察到的细菌分布模式进行比较。使用荧光原位杂交对细菌进行可视化。

结果

长卷曲状细菌在中等粘度凝胶中移动最佳,短杆菌和球菌更喜欢低粘性环境,而高粘度则使所有细菌群体都固定不动。小鼠结肠中细菌的空间分布也取决于形状而非分类学,这表明黏液层内存在垂直(从表面到管腔)和纵向(从近端结肠到远端结肠)的粘度梯度。我们的结果表明,杯状细胞、隐窝底部和靠近肠腔处的黏液粘度较低,而与柱状上皮相邻的部位黏液粘度较高。黏液粘度向远端结肠逐渐增加,在近端结肠对细菌进行选择性分离,在远端结肠则完全分离。

结论

黏液分泌和脱水的位点特异性调节使得黏液层在靠近肠黏膜的区域变得坚实且细菌无法穿透,但在与管腔内容物相邻的区域则变得疏松且具有润滑性。黏液分泌和脱水的选择性控制可能是涉及肠道病原体的慢性疾病管理中的一个关键因素。

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