Role of Intestinal Microbiota in Ulcerative Colitis
Role of Intestinal Microbiota in Ulcerative Colitis Role of Intestinal Microbiota in Ulcerative Colitis
Theoretical part 12 2. The colonic environment 2.3. Difference in microbial community Even though several species of the colon are able to inhabit both the mucosal and the luminal environment, the mucosal microbial community has shown to differ from the luminal community (Zoetendal et al., 2002;Macfarlane et al., 2005;Macfarlane, 2008;Van den Abbeele et al., 2011a). Additionally, literature have revealed that dominant phylogenetic groups of mucosal microbial communities are similar in the ascending colon, descending colon, and rectum, but with high inter‐ individual variations (Zoetendal et al., 2002;Lepage et al., 2005;Eckburg et al., 2005;Wang et al., 2005a). In contrast, it has been demonstrated that luminal microbial communities differ depending on colonic region (Pochart et al., 1993;Marteau et al., 2001). This suggests that different environmental conditions found throughout the colonic lumen (described in section 1.2) may affect the composition of luminal bacteria, whereas the composition of mucosal bacteria is more influenced by host factors (described section 2.1). It is also plausible that the niches of the lumen and the mucus select a microbial population that may display different roles in the host. A recent study by Derrien et al. (2011) has demonstrated that germ‐free mice mono‐cultured with Akkermansia muciniphila (Gram‐negative, strictly anaerobic mucin‐degrading bacterium) or Lactobacillus plantanum (Gram‐ positive bacterium that utilize dietary carbohydrates but is incapable of utilizing mucin) led to different mucosal transcriptome changes depending on colonization of the different bacteria. L. plantarum was exclusively located in the colonic lumen and induced expression of genes involved in regulation of lipid and fatty acid metabolism, whereas A. muciniphila colonized the colonic mucus of the mice and induced expression of genes involved in regulatory immune processes. These results could imply that the mucosal microbiota are more involved in interaction with epithelial and immune cells compared to the luminal microbiota, since they reside closer to the IECs. Hence, the difference in bacterial community structure is likely driven by factors such as differential substrate availability (e.g. mucus versus undigested dietary residues) and host‐microbe interactions. Figure 3 illustrates the mucosa and lumen of the colon.
Theoretical part Figure 3: The colonic mucosa with epithelium and two mucus layers, and the lumen. 13 2. The colonic environment 2.4. Interaction between host and commensal bacteria The molecular mechanisms responsible for the host to tolerate the presence of commensals that being both the luminal and mucosal bacteria are not fully understood (Macpherson et al., 2005), but the ability of the host’s mucosal immune system to distinguish between commensal and pathogenic bacteria using a limited number of pattern‐recognition receptors (PRRs) is believed to play a role (Sanz and De Palma, 2009;Van den Abbeele et al., 2011b). PRRs are germline‐encoded receptors, which can recognize conserved molecular patterns (pathogen‐associated molecular patterns (PAMPs) or microorganism‐associated molecular patterns (MAMPs)), which are essential for the survival of microorganism and therefore difficult for the microorganism to alter (Akira and Takeda, 2004;Van den Abbeele et al., 2011b). PRRs are expressed by innate immune cells including macrophages and dendritic cells (DCs), by adaptive immune cells such as T cells, and by nonprofessional cells such as IECs, and are crucial for the initial recognition of microorganisms (Akira and Takeda, 2004;Round et al., 2011). The best characterized class of PRRs is Toll‐like receptors (TLRs). Eleven members of the TLR family have been identified in mammals, and different TLRs react with specific PAMPs or MAMPs, allowing the host to distinguish between self and foreign pathogens. Table 2 demonstrates the different TLRs and their ligands (Bacterial origin). As commensal and pathogenic bacteria produce similar ligands sensed by TLRs, epithelial and immune cells have to have mechanisms which avoid commensals to trigger hyper‐responsiveness (Lebeer et al., 2010). A wide variety of bacterial species residing within the human colon are Gram‐ positive bacteria (Section 1.1). In the cell wall of Gram‐positive bacteria, lipoteichoic acids (LTA) are embedded in a thick layer of peptidoglycan (PG). As shown in Table 2, LTA are ligand for TLR2.
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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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Theoretical part<br />
Figure 3: The colonic mucosa with epithelium and two mucus layers, and the lumen.<br />
13<br />
2. The colonic environment<br />
2.4. Interaction between host and commensal bacteria<br />
The molecular mechanisms responsible for the host to tolerate the presence <strong>of</strong> commensals that<br />
be<strong>in</strong>g both the lum<strong>in</strong>al and mucosal bacteria are not fully understood (Macpherson et al., 2005),<br />
but the ability <strong>of</strong> the host’s mucosal immune system to dist<strong>in</strong>guish between commensal and<br />
pathogenic bacteria us<strong>in</strong>g a limited number <strong>of</strong> pattern‐recognition receptors (PRRs) is believed to<br />
play a role (Sanz and De Palma, 2009;Van den Abbeele et al., 2011b). PRRs are germl<strong>in</strong>e‐encoded<br />
receptors, which can recognize conserved molecular patterns (pathogen‐associated molecular<br />
patterns (PAMPs) or microorganism‐associated molecular patterns (MAMPs)), which are essential<br />
for the survival <strong>of</strong> microorganism and therefore difficult for the microorganism to alter (Akira and<br />
Takeda, 2004;Van den Abbeele et al., 2011b). PRRs are expressed by <strong>in</strong>nate immune cells <strong>in</strong>clud<strong>in</strong>g<br />
macrophages and dendritic cells (DCs), by adaptive immune cells such as T cells, and by<br />
nonpr<strong>of</strong>essional cells such as IECs, and are crucial for the <strong>in</strong>itial recognition <strong>of</strong> microorganisms<br />
(Akira and Takeda, 2004;Round et al., 2011). The best characterized class <strong>of</strong> PRRs is Toll‐like<br />
receptors (TLRs). Eleven members <strong>of</strong> the TLR family have been identified <strong>in</strong> mammals, and<br />
different TLRs react with specific PAMPs or MAMPs, allow<strong>in</strong>g the host to dist<strong>in</strong>guish between self<br />
and foreign pathogens. Table 2 demonstrates the different TLRs and their ligands (Bacterial orig<strong>in</strong>).<br />
As commensal and pathogenic bacteria produce similar ligands sensed by TLRs, epithelial and<br />
immune cells have to have mechanisms which avoid commensals to trigger hyper‐responsiveness<br />
(Lebeer et al., 2010). A wide variety <strong>of</strong> bacterial species resid<strong>in</strong>g with<strong>in</strong> the human colon are Gram‐<br />
positive bacteria (Section 1.1). In the cell wall <strong>of</strong> Gram‐positive bacteria, lipoteichoic acids (LTA)<br />
are embedded <strong>in</strong> a thick layer <strong>of</strong> peptidoglycan (PG). As shown <strong>in</strong> Table 2, LTA are ligand for TLR2.