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Proximal colon–derived O-glycosylated mucus encapsulates and modulates the microbiota
Science ( IF 44.7 ) Pub Date : 2020-10-22 , DOI: 10.1126/science.aay7367
Kirk Bergstrom 1, 2 , Xindi Shan 1 , David Casero 3 , Albert Batushansky 4 , Venu Lagishetty 5 , Jonathan P Jacobs 6 , Christopher Hoover 1 , Yuji Kondo 1 , Bojing Shao 1 , Liang Gao 1 , Wesley Zandberg 7 , Benjamin Noyovitz 7 , J Michael McDaniel 1 , Deanna L Gibson 2 , Sepideh Pakpour 8 , Negin Kazemian 8 , Samuel McGee 1 , Courtney W Houchen 9 , Chinthalapally V Rao 9 , Timothy M Griffin 4, 10 , Justin L Sonnenburg 11 , Rodger P McEver 1, 10 , Jonathan Braun 3 , Lijun Xia 1, 10
Affiliation  

So much more to mucus Mammals accommodate a dense community of metabolically active microorganisms in their gut. This is not a passive relationship, and host and microbe have antagonistic as well as mutualistic responses to each other. Using a whole-colon imaging method in mice, Bergstrom et al. looked at the role of colonic mucus in segregating the microbiota from host cells during elimination of feces (see the Perspective by Birchenough and Johansson). Host goblet cells synthesize two forms of mucin that differ in branched chain O-glycosylation and the site of production in the colon. A “thick” mucus in the proximal, ascending colon wraps the microbiota to form fecal pellets. Transit along the distal, descending colon is lubricated by “thin” mucus that transiently links with the thick mucus. Normal mucus encapsulation prevents inflammation and hyperplasia and thus is important for maintenance of a healthy gut. Science, this issue p. 467; see also p. 402 O-glycan–rich mucus secretion segregates colon microbiota from host cells to prevent inflammation during fecal elimination. Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to the major form. The microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells. In turn, O-glycans on proximal colon–derived Muc2 modulate the structure and function of the microbiota as well as transcription in the colon mucosa. Our work shows how proximal colon control of mucin production is an important element in the regulation of host-microbiota symbiosis.

中文翻译:

近端结肠衍生的 O-糖基化粘液包裹并调节微生物群

对粘液而言,哺乳动物的肠道内含有密集的代谢活跃微生物群落。这不是一种被动的关系,宿主和微生物之间既有对立的反应,也有互惠的反应。Bergstrom 等人在小鼠中使用全结肠成像方法。研究了在消除粪便过程中结肠粘液在将微生物群与宿主细胞分离中的作用(参见 Birchenough 和 Johansson 的观点)。宿主杯状细胞合成两种形式的粘蛋白,它们的支链 O-糖基化和结肠中的生产位点不同。近端升结肠中的“厚”粘液包裹着微生物群,形成粪便颗粒。沿着远端的降结肠通过“稀”粘液润滑,该粘液与稠粘液短暂连接。正常的粘液包裹可防止炎症和增生,因此对于维持健康的肠道很重要。科学,本期第 3 页。467; 另见第 402 富含 O-聚糖的粘液​​分泌将结肠微生物群与宿主细胞分离,以防止粪便排泄过程中的炎症。结肠粘液将肠道微生物群与宿主组织分离,但它如何组织在整个结肠中发挥作用尚不清楚。在小鼠中,我们发现结肠粘液由两种不同的 O-糖基化的 Muc2 实体组成:一种由近端结肠产生的主要形式,它包裹着包括微生物群在内的粪便物质,另一种来自远端结肠的次要形式,它附着在主要形式。微生物群通过诱导近端结肠杯状细胞产生 Muc2 来指导其自身的封装。反过来,近端结肠衍生的 Muc2 上的 O-聚糖调节微生物群的结构和功能以及结肠粘膜中的转录。我们的工作表明近端结肠控制粘蛋白产生是调节宿主-微生物群共生的重要因素。
更新日期:2020-10-22
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