Role of Intestinal Microbiota in Ulcerative Colitis
Role of Intestinal Microbiota in Ulcerative Colitis Role of Intestinal Microbiota in Ulcerative Colitis
A Theoretical part 1. The intestinal environment Figure 2: A) Anatomy of the colon with fermentation sites and metabolic activity. Adapted from Vernazza et al. (2006) and B) Cross‐section of the colon wall illustrating lumen, mucosa, submucosa, muscolaris externa and serosa (Myers, 2007). 6 B
2. The colonic environment Theoretical part 7 2. The colonic environment The commensal bacteria who inhabit the colon are either located in the lumen or in the mucus. They are believed to play an important role in their specific environment, although it is not fully understood what selects the mucosal and luminal bacterial communities. A recent review by Van den Abbeele et al. (2011b) has suggested following hypothesis: “Microorganisms who are not targeted by host defense molecules upon colonization of the mucus layer, are able to reside in the mucosa associated microbial community, and commensals who are preferentially targeted by host defense molecules in the mucus layer, are restricted to the lumen”. A description of the mucosal and luminal environment will be given in the following chapter and in addition, the role of the two microbial communities and how they interact with the host will be addressed. 2.1. The mucosal environment The mucus layer covering the colonic epithelium results in a physical network that separates the lumen intestinal residents and pathogens from the host. The mucus layer can respond dynamically to infection, and is regulated by the underlying innate and adaptive immune system (McGuckin et al., 2011). The colonic mucus constitutes a complex fluid, which is rich in gel‐forming mucins. The mucins are large glycoproteins characterized by abundant and variable O‐linked glycans attached to hydroxy amino acids clustered in PTS domains (high frequency of the amino acids proline, threonine, and serine). Sulfate residues and O‐acetyl‐substituted sialic acid can be found on the terminal oligosaccharides of the glycans (Lang et al., 2007;Johansson et al., 2011;McGuckin et al., 2011). The glycans are an important energy source for mucosal bacteria and are used as adhesion sites for bacteria (Hansson and Johansson, 2010c;Johansson et al., 2011). However, they also serve a different role. They protect the protein core from proteases, preserving the integrity of the mucin polymer and due to their complex structure, decrease the number of bacteria able to grow on mucin (Moncada et al., 2003). The thickness of the colonic mucus is 700 μm and consists of two layers. The thin inner layer is a firmly adherent gel, which is physically difficult to dislodge and devoid of bacteria (Johansson et al., 2008;Hansson and Johansson, 2010b). The thick outer layer, on the other hand, is a loosely adherent gel, which is more easily dispersed, colonized and degraded by bacteria (Atuma et al.,
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- Page 6 and 7: Preface Preface This thesis present
- Page 8 and 9: Summary Summary The microbiota of t
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- Page 12 and 13: Introduction and objectives Introdu
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- Page 18 and 19: List of Centents Methodology append
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2. The colonic environment<br />
Theoretical part<br />
7<br />
2. The colonic environment<br />
The commensal bacteria who <strong>in</strong>habit the colon are either located <strong>in</strong> the lumen or <strong>in</strong> the mucus.<br />
They are believed to play an important role <strong>in</strong> their specific environment, although it is not fully<br />
understood what selects the mucosal and lum<strong>in</strong>al bacterial communities. A recent review by Van<br />
den Abbeele et al. (2011b) has suggested follow<strong>in</strong>g hypothesis:<br />
“Microorganisms who are not targeted by host defense molecules upon colonization <strong>of</strong> the mucus<br />
layer, are able to reside <strong>in</strong> the mucosa associated microbial community, and commensals who are<br />
preferentially targeted by host defense molecules <strong>in</strong> the mucus layer, are restricted to the lumen”.<br />
A description <strong>of</strong> the mucosal and lum<strong>in</strong>al environment will be given <strong>in</strong> the follow<strong>in</strong>g chapter and <strong>in</strong><br />
addition, the role <strong>of</strong> the two microbial communities and how they <strong>in</strong>teract with the host will be<br />
addressed.<br />
2.1. The mucosal environment<br />
The mucus layer cover<strong>in</strong>g the colonic epithelium results <strong>in</strong> a physical network that separates the<br />
lumen <strong>in</strong>test<strong>in</strong>al residents and pathogens from the host. The mucus layer can respond dynamically<br />
to <strong>in</strong>fection, and is regulated by the underly<strong>in</strong>g <strong>in</strong>nate and adaptive immune system (McGuck<strong>in</strong> et<br />
al., 2011). The colonic mucus constitutes a complex fluid, which is rich <strong>in</strong> gel‐form<strong>in</strong>g muc<strong>in</strong>s. The<br />
muc<strong>in</strong>s are large glycoprote<strong>in</strong>s characterized by abundant and variable O‐l<strong>in</strong>ked glycans attached<br />
to hydroxy am<strong>in</strong>o acids clustered <strong>in</strong> PTS doma<strong>in</strong>s (high frequency <strong>of</strong> the am<strong>in</strong>o acids prol<strong>in</strong>e,<br />
threon<strong>in</strong>e, and ser<strong>in</strong>e). Sulfate residues and O‐acetyl‐substituted sialic acid can be found on the<br />
term<strong>in</strong>al oligosaccharides <strong>of</strong> the glycans (Lang et al., 2007;Johansson et al., 2011;McGuck<strong>in</strong> et al.,<br />
2011). The glycans are an important energy source for mucosal bacteria and are used as adhesion<br />
sites for bacteria (Hansson and Johansson, 2010c;Johansson et al., 2011). However, they also serve<br />
a different role. They protect the prote<strong>in</strong> core from proteases, preserv<strong>in</strong>g the <strong>in</strong>tegrity <strong>of</strong> the<br />
muc<strong>in</strong> polymer and due to their complex structure, decrease the number <strong>of</strong> bacteria able to grow<br />
on muc<strong>in</strong> (Moncada et al., 2003).<br />
The thickness <strong>of</strong> the colonic mucus is 700 μm and consists <strong>of</strong> two layers. The th<strong>in</strong> <strong>in</strong>ner layer is a<br />
firmly adherent gel, which is physically difficult to dislodge and devoid <strong>of</strong> bacteria (Johansson et<br />
al., 2008;Hansson and Johansson, 2010b). The thick outer layer, on the other hand, is a loosely<br />
adherent gel, which is more easily dispersed, colonized and degraded by bacteria (Atuma et al.,