Role of Intestinal Microbiota in Ulcerative Colitis

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Theoretical part 4 1. The intestinal environment Metagenomic studies have revealed that the majority of gut microbiota sequences belong to the Bacteria, reflecting their predominance in the human adult gut (Eckburg et al., 2005;Qin et al., 2010;Arumugam et al., 2011). Despite the complexity of the human intestinal ecosystem, the majority of the bacteria are members of only a limited number of dominating bacterial phyla, such as Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, Verrucomicrobia, and Fusobacteria with Firmicutes, and Bacteroidetes being the most abundant phyla (Figure 1)(Eckburg et al., 2005;Tap et al., 2009;Arumugam et al., 2011). Within the Firmicutes phylum, 95% of the phylogenetic types are members of the Clostridia class, and of these a substantial number are related to butyrate‐producing bacteria, all of which fall within the clostridial clusters IV, XIVa, and XVI (Eckburg et al., 2005;Tap et al., 2009). At genus level, Bacteroides has shown to be the most abundant genus in the human gut microbiota of adults, followed by the genera Faecalibacterium, Bifidobacterium, Lachnospiraceae, Roseburia, and Alistipes (Arumugam et al., 2011). Another genus normally detected in the human gut is Lactobacillus, although only present in low levels depending on age and individuals (Mueller et al., 2006;Frank et al., 2007). Figure 1: The microbial diversity of the main phylotypes in the human intestinal microbiota (Turroni et al., 2009).
Theoretical part 5 1. The intestinal environment 1.2. Function and physiology of the large intestine The main functions of the large intestine are food storage, absorption of water and electrolytes, and digestion of indigestible carbohydrates by the colonic microbiota (Vander et al., 1998). Anatomically, the large intestine consists of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum (Guarner and Malagelada, 2003). The ascending colon is a saccharolytic environment where most bacterial metabolic activity and carbohydrate fermentation occur. The pH of the ascending colon is generally lower (approximately 5‐6) than that of the distal colon. The reduced pH is considered to be the result of carbohydrate fermentation, which gives rise to the production of Short‐Chain Fatty Acids (SCFAs) (Macfarlane et al., 1992). Consequently, the carbohydrate availability decreases in the descending colon, which leads to a pH close to neutral. The rate of bacterial metabolism is lower, and protein and amino acids become a more dominant metabolic energy source for bacteria (Figure 2A) (Guarner and Malagelada, 2003;Vernazza et al., 2006). Anaerobic fermentation of proteins by the microbiota produces branched SCFAs, however, it also generates a series of potentially toxic compounds such as ammonia, amines, and phenolic compounds (Vernazza et al., 2006). The wall of the colon consists of four tissue compartments (Figure 2B): mucosa, submucosa, muscularis externa, and serosa. The mucosa consists of a mucus layer, single layer of epithelium, the lamina propria, and a thin muscle layer (muscularis mucosae). The epithelium covering the mucosa consists of different types of cells, namely goblet cells (mucin secreting cells), enterocytes (absorptive cells), and endocrine cells (hormone secreting cells). These cells are linked together along the edges of their luminal surface by tight junctions. The submucosa is a connective tissue supporting the mucosa with blood vessels, lymphatic vessels, and nerves. The muscularis externa consists of two muscle layers: the longitudinal and the smooth muscle layer. Between the two muscle layers is a network of nerves (the myenteric nerve plexus). The serosa is the outer connective tissue layer, which connects the colon to the abdominal cavity (Vander et al., 1998).
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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
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Page 16 and 17: List of contents List of Centents P
Page 18 and 19: List of Centents Methodology append
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Page 27 and 28: Theoretical part 9 2. The colonic e
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Page 31 and 32: Theoretical part Figure 3: The colo
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Page 37 and 38: Theoretical part 19 4. Modulation o
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Page 62 and 63: Abstract Background Detailed knowle
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layer of UC patients and found that
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Acknowledgements The authors thank
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Table 2 ‐ 16S rRNA gene and 16S
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1. Firmicutes phylum 2. Bacteroidet
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Supplementary Figure S1. Dice clust
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Reference List 1. Ahmed S, Macfarla
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32. Matsuki T, Watanabe K, Fujimoto
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Methodology part Paper 2 Fecal lact
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Fecal lactobacilli and bifidobacter
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Introduction The mucus layer lining
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efore enrolment and there was no si
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(Bio‐Rad Labs, Hercules, Californ
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Microbial community analysis using
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difference from the luminal microbi
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that C. coccoides group and C. lept
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Table 1 ‐ 16S rRNA gene of phylum
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Table 2 ‐ Preference of bacterial
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Figure 1. A) Schematic overview of
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A. B. Figure 3. Principal component
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15. Fooks LJ, Gibson GR. (2002) In
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47. Ouwehand AC, Suomalainen T, Tol
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Methodology part Paper 3 Paper 3 In
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APPLIED AND ENVIRONMENTAL MICROBIOL
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8338 VIGSNÆS ET AL. APPL. ENVIRON.
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Methodology part Introduction The a
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Journal of Agricultural and Food Ch
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Methodology part Paper 5 Paper 5 Ma
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Appl Microbiol Biotechnol (2011) 90
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Methodology part Paper 6 Tailored e
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Process Biochemistry 46 (2011) 1039
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Table 1 List of enzymes. Enzyme Sou
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J. Holck et al. / Process Biochemis
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Intensity 50 0 C1 175.05 J. Holck e
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J. Holck et al. / Process Biochemis
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[29] Bauer S, Vasu P, Persson S, Mo
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Methodology part 150
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Methodology part 152 Appendix 1 hor
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Appendix 3 Methodology part Appendi
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Methodology part 156 Appendix 3
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7. Discussion and perspectives Disc
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Discussion and conclusion 161 7. Di
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References References Abreu,M.T., V
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References Derrien,M., Vaughan,E.E.
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References Haarman,M. and Knol,J. (
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References Lantz,P.G., Matsson,M.,
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References Matsuki,T., Watanabe,K.,
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References Pullan,R.D., Thomas,G.A.
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References Tannock,G.W. (2010). Ana
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National Food Institute Technical U
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Role of Intestinal Microbiota in Ulcerative Colitis

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