Role of Intestinal Microbiota in Ulcerative Colitis
Role of Intestinal Microbiota in Ulcerative Colitis Role of Intestinal Microbiota in Ulcerative Colitis
Theoretical part Figure 4: Location of UC in the different colon regions (Longstreth et al., 2010) 16 3. Inflammatory Bowel disease The factors responsible for the initiation and perpetuation of UC are unknown (Loftus, 2004;Sartor, 2006). However, evidence suggests that the colonic host‐bacterial interaction and microbial composition play a pivotal role in the pathogenesis of UC. Firstly, the colon is the area of the gut with the highest bacterial concentrations (section 1.1) and is also the site where inflammation occurs in UC patients. Secondly, genetically engineered germ‐free mice, rats, and guinea pigs completely lack enterocolitis but develop intestinal inflammation within 1 – 4 weeks if they are colonized with conventional gut bacteria (Himmel et al., 2008;Sartor, 2008). Thirdly, clinical studies have revealed that some PRRs have gene mutations (e.g. TRL9) or an increased expression on IECs (e.g. TLR2 and TLR4) in UC patients (De Jager et al., 2007;Frolova et al., 2008;Fuse et al., 2010), and finally, studies have shown that UC patients in relapse have a colonic mucus layer that has an altered O‐glycan profile and is significantly thinner compared to healthy subjects (Pullan et al., 1994;Larsson et al., 2011). Thus, gut host‐bacterial interaction seems to be disturbed in UC, which may have consequences for the composition of the gut commensal bacteria. 3.2. Alteration in the bacterial community of ulcerative colitis patients Compositional changes in the colonic microbiota have been observed when comparing fecal and mucosal samples from UC patients to that of healthy subjects (Lepage et al., 2005;Frank et al., 2007;Takaishi et al., 2008;Sokol et al., 2009;Qin et al., 2010). Studies have demonstrated that the fecal and mucosal amount of Firmicutes was significantly lower in UC patients than in healthy subjects (Frank et al., 2007;Sokol et al., 2009). This was also applicable for the two dominant
Theoretical part 17 3. Inflammatory Bowel disease clostridial groups within the Firmicutes phylum, Clostridium coccoides group and Clostridium leptum subgroup (Frank et al., 2007;Takaishi et al., 2008;Sokol et al., 2009). Takiashi et al. (2008) have also shown that these two clostridial groups were significantly less abundant in fecal samples from UC patients in relapse compared to UC patients in remission. Studies have also demonstrated that the Bacteroidetes phylum was underrepresented in mucosal samples from UC patients compared to healthy subjects (Ott et al., 2004;Frank et al., 2007), and that the amount of Bacteroides fragilis group was low in fecal and mucosal samples from UC patients (Takaishi et al., 2008). A common genus from the gut community, Bifidobacterium spp., has shown to be underrepresented in mucosal and fecal samples from UC patients compared to healthy subjects (Macfarlane et al., 2004;Mylonaki et al., 2005;Sokol et al., 2009). Additionally, Mylonaki et al. (2005) revealed that bifidobacteria were significantly less abundant in mucosal samples from UC patients in remission and relapse than in healthy subjects. Bacteria that have shown to be increased in mucosal samples from UC patients than in healthy subjects include the sulphate‐ reducing bacteria Desulfovibrio spp. (belongs to the delta proteobacteria) (Rowan et al., 2010), and the phylum Proteobacteria (Lepage et al., 2005;Frank et al., 2007).
- Page 1: Role of Intestinal Microbiota in Ul
- Page 4 and 5: Role of Intestinal Microbiota in Ul
- Page 6 and 7: Preface Preface This thesis present
- Page 8 and 9: Summary Summary The microbiota of t
- Page 10 and 11: Dansk sammendrag Dansk sammendrag M
- Page 12 and 13: Introduction and objectives Introdu
- Page 14 and 15: List of Manuscripts Not included in
- Page 16 and 17: List of contents List of Centents P
- Page 18 and 19: List of Centents Methodology append
- Page 21 and 22: 1. The intestinal environment Theor
- Page 23 and 24: Theoretical part 5 1. The intestina
- Page 25 and 26: 2. The colonic environment Theoreti
- Page 27 and 28: Theoretical part 9 2. The colonic e
- Page 29 and 30: Table 1: The presence of glycoside
- Page 31 and 32: Theoretical part Figure 3: The colo
- Page 33: 3. Inflammatory Bowel disease Theor
- Page 37 and 38: Theoretical part 19 4. Modulation o
- Page 39 and 40: Theoretical part 21 4. Modulation o
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- Page 43 and 44: Table 4: Clinical trials on the pre
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- Page 51: Methodology part
- Page 54 and 55: Methodology part 6. Methodology, co
- Page 56 and 57: Methodology part 6. Methodology, co
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- Page 60 and 61: Introduction Methodology part 42 Pa
- Page 62 and 63: Abstract Background Detailed knowle
- Page 64 and 65: depending the level of disease acti
- Page 66 and 67: in 1 x TAE at 60 °C for 16 h at 36
- Page 68 and 69: Statistics PCA were generated by SA
- Page 70 and 71: The PCA of the Gram‐positive bact
- Page 72 and 73: layer of UC patients and found that
- Page 74 and 75: Acknowledgements The authors thank
- Page 76 and 77: Table 2 ‐ 16S rRNA gene and 16S
- Page 78 and 79: 1. Firmicutes phylum 2. Bacteroidet
- Page 80 and 81: Supplementary Figure S1. Dice clust
- Page 82 and 83: Reference List 1. Ahmed S, Macfarla
Theoretical part<br />
17<br />
3. Inflammatory Bowel disease<br />
clostridial groups with<strong>in</strong> the Firmicutes phylum, Clostridium coccoides group and Clostridium<br />
leptum subgroup (Frank et al., 2007;Takaishi et al., 2008;Sokol et al., 2009). Takiashi et al. (2008)<br />
have also shown that these two clostridial groups were significantly less abundant <strong>in</strong> fecal samples<br />
from UC patients <strong>in</strong> relapse compared to UC patients <strong>in</strong> remission. Studies have also demonstrated<br />
that the Bacteroidetes phylum was underrepresented <strong>in</strong> mucosal samples from UC patients<br />
compared to healthy subjects (Ott et al., 2004;Frank et al., 2007), and that the amount <strong>of</strong><br />
Bacteroides fragilis group was low <strong>in</strong> fecal and mucosal samples from UC patients (Takaishi et al.,<br />
2008). A common genus from the gut community, Bifidobacterium spp., has shown to be<br />
underrepresented <strong>in</strong> mucosal and fecal samples from UC patients compared to healthy subjects<br />
(Macfarlane et al., 2004;Mylonaki et al., 2005;Sokol et al., 2009). Additionally, Mylonaki et al.<br />
(2005) revealed that bifidobacteria were significantly less abundant <strong>in</strong> mucosal samples from UC<br />
patients <strong>in</strong> remission and relapse than <strong>in</strong> healthy subjects. Bacteria that have shown to be<br />
<strong>in</strong>creased <strong>in</strong> mucosal samples from UC patients than <strong>in</strong> healthy subjects <strong>in</strong>clude the sulphate‐<br />
reduc<strong>in</strong>g bacteria Desulfovibrio spp. (belongs to the delta proteobacteria) (Rowan et al., 2010),<br />
and the phylum Proteobacteria (Lepage et al., 2005;Frank et al., 2007).