Forming a mucus barrier along the colon

doi:10.1126/science.abe7194

GSTDTAP > 气候变化

DOI	10.1126/science.abe7194
	Forming a mucus barrier along the colon
	George M. H. Birchenough; Malin E. V. Johansson
	2020-10-23
发表期刊	Science
出版年	2020
英文摘要	The intestine is exposed to numerous hazards and is heavily colonized by microorganisms. This requires a balanced protective system, which includes secreted mucus layers that play an important role in keeping luminal contents, including bacteria, separated from the epithelium ([ 1 ][1]). Intestinal mucus contains many different proteins, and the densely O-glycosylated mucin 2 (MUC2) is the core molecule ([ 2 ][2], [ 3 ][3]). Colonic mucus defects that allow bacteria to reach the epithelium have been associated with colitis ([ 4 ][4]). On page 467 of this issue, Bergstrom et al. ([ 5 ][5]) expand our understanding of the colonic mucus system by showing that mucus from proximal colonic regions contributes extensively to forming the protective barrier in the distal colon. This work highlights the role of the colonic tissue as a whole in driving mucus barrier formation and indicates the potential for regionally targeted therapeutic interventions in intestinal disease. Mucus coating on distal colonic fecal material has been previously observed ([ 6 ][6]), but Bergstrom et al. used glycan-specific lectin staining of fixed whole mouse colons to differentiate between differently O-glycosylated mucus originating from proximal and distal colonic regions. They found that proximal colon–derived mucus primarily encapsulates fecal pellets as they form and is further strengthened by a secondary encapsulation of mucus produced in the distal colon. Thus, mucus from both regions is associated with the excreted pellet. The authors showed that regions between pellets normally harbor relatively low numbers of bacteria compared with mucus-encapsulated pellets. Inducing mucus defects in the proximal or distal colon of mice increased the bacterial load in areas between pellets. This enhanced contact between uncontained bacteria and the epithelium led to inflammation that was most pronounced in the distal colon. Simultaneous disruption of the proximal- and distal-derived mucus resulted in severe loss of barrier function, highlighting the need for cooperation between proximal and distal mucus production in maintaining the protective barrier. It should be noted that analysis of mucus in fixed tissue sections is challenging because secreted mucus is highly hydrated and shrinks upon exposure to chemical fixatives. In addition, secreted mucus is rarely preserved in fixed intestinal tissue that does not contain fecal material. Indeed, analysis of mucus in live tissue demonstrates that it forms a continuous attached layer on the epithelium throughout the intestine ([ 7 ][7]–[ 9 ][8]). This attached mucus contains several components that restrict direct bacterial contact as part of its protective properties ([ 9 ][8], [ 10 ][9]). By combining our current understanding of the mucus system with the findings of Bergstrom et al. , it is likely that the in vivo mucus barrier comprises an attached mucus layer that covers the epithelium as a local barrier, which is detached gradually and thereby continuously added to the passing fecal pellets (see the figure). ![Figure][10] The mucus barrier Continuous colonic mucus barrier formation along the proximal-distal axis is required for efective barrier function and results in the formation of distinct microbial niche environments. GRAPHIC: V. ALTOUNIAN/ SCIENCE With regard to microbiota-mucus interactions, Bergstrom et al. found that formation of the proximal-derived, but not the distal-derived, mucus layer was dependent on bacterial colonization. This effect was not mediated by inflammasomes (innate immune signaling complexes that can play a role in microbe-dependent mucus secretion), suggesting a mechanism different from the fast mucus secretory response to bacteria mediated by microbe-sensing sentinel goblet cells within the colonic epithelium ([ 11 ][11]). The proximal mucus also had marked effects on microbiota composition and metabolism. Mucus alterations in the proximal colon would likely have effects on the mucus niche–associated resident microbiota that are found in the folds of the proximal colon and are thought to have a more intimate relationship with the host than the transient microbiota ([ 12 ][12]). The high load of propagating bacteria in the proximal colon combined with mucus and bacteria from the small intestine and cecum make up the bulk of the fecal pellets in mice. However, there are also mucus-associated bacteria along the length of the intestine that differ in composition from the bulk material found in the fecal stream ([ 13 ][13]). Bergstrom et al. and others ([ 6 ][6]) have noted the paucity of bacteria in the interpellet regions in histological sections; however, live imaging and quantitative and qualitative microbiota characterization have indicated the presence of a robust bacterial community that is dominated by mucus specialists (e.g., Mucispirillum ) ([ 9 ][8]). This mucus-associated community likely represents the distal colonic equivalent of the resident microbiota in the proximal colon, and it probably undergoes interactions with host tissues distinct from those between the encapsulated pellet microbiota and host tissues. Loss of the distinction between mucus-associated and encapsulated bacteria may be associated with disease. The mucus barrier is a critical defensive system that inhibits the interaction of pathogens with the intestinal epithelium. However, many specialized intestinal pathogens have evolved mechanisms that allow them to penetrate the mucus barrier and initiate mucosal infections ([ 14 ][14]). The study of Bergstrom et al. raises questions about the spatiotemporal pathogenesis of these infections. For example, does an intestinal pathogen that infects the distal colon first have to escape mucus encapsulation in the proximal colon? Or must separate strategies be employed to penetrate proximally and distally derived mucus barriers that have distinct properties? Bergstrom et al. also detected mucus layer coating of excreted fecal material in both baboons and humans ([ 5 ][5]). The colonic regional origin of the mucus in these samples was not determined; however, it is possible that an analogous continual mucus encapsulation process is active in humans. It is also possible that differences in function, motility, total transit time, and luminal consistency could result in more species-specific solutions to protect the epithelium. In humans, the relatively long exposure to the fecal material and its much higher water content likely give rise to different demands for the mucosal surface. Similarly, mucus secreted in the more proximal elements of the human intestine is exposed to the degradative action of bacteria for a longer period than in mice. In this context, locally produced mucus protection in the human distal colon could be even more crucial for health. Further investigation of how the mucus system works throughout the colon in humans is critical to provide targeted aid to the increasing number of people with intestinal disorders. 1. [↵][15]1. M. E. Johansson et al ., Proc. Natl. Acad. Sci. U.S.A. 105, 15064 (2008). [OpenUrl][16][Abstract/FREE Full Text][17] 2. [↵][18]1. A. M. Rodríguez-Piñeiro et al ., Am. J. Physiol. 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领域	气候变化 ; 资源环境
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/300279
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	George M. H. Birchenough,Malin E. V. Johansson. Forming a mucus barrier along the colon[J]. Science,2020.
APA	George M. H. Birchenough,&Malin E. V. Johansson.(2020).Forming a mucus barrier along the colon.Science.
MLA	George M. H. Birchenough,et al."Forming a mucus barrier along the colon".Science (2020).