Role of Intestinal Microbiota in Ulcerative Colitis
Role of Intestinal Microbiota in Ulcerative Colitis Role of Intestinal Microbiota in Ulcerative Colitis
Theoretical part 8 2. The colonic environment 2001;Johansson et al., 2008). The mucus gel also provides a matrix for the retention of anti‐ microbial molecules and secretory immunoglobulin A (IgA). The antimicrobial peptides are produced by the colonic epithelial cells, and include among others β‐defensins and cathelicidin LL37 (Hase et al., 2002;Tollin et al., 2003), and the secretory IgA is synthesized by plasma cells in the lamina propria. The commensal bacteria colonizing the outer mucus layer have evolved different microbial characteristics, which contribute to a specific selected mucosal community. Firstly, the bacteria have to carry adhesion molecules to bind to the mucus (Laparra and Sanz, 2009;Kankainen et al., 2009;Johansson et al., 2011). Cell surface components that promote the adherence of commensal bacteria to mucus include among others; fimbriae (Schell et al., 2002;Kline et al., 2009;Kankainen et al., 2009), elongation factor Tu (EF‐TU) (Granato et al., 2004;Gilad et al., 2011), extracellular mucus‐binding protein (Mub, found in Lactobacillus spp.) (Roos and Jonsson, 2002) and lectin‐like mannosespecific adhesin (Msa, found in Lactobacillus spp.) (Pretzer et al., 2005). Secondly, the bacteria have to have the ability to gain nutrients from the host‐derived mucins by synthesizing mucin‐degrading enzymes. This often involves the combined action of bacterial proteases, glycosidases, sialidases and sulphatases, due to the complex structure of mucin (Killer and Marounek, 2011). A variety of bacteria are able to produce one or more of the mucin‐degrading enzymes, which include Akkermansia muciniphila and species of Bifidobacterium, Bacteroides, Prevotella, and Ruminococcus (Bayliss and Houston, 1984;Wright et al., 2000;Derrien et al., 2004;Killer and Marounek, 2011). Thirdly, the bacteria have to be able to survive in the presence of an oxygen gradient along the mucus layer, as oxygen is continuously released from the blood (Van den Abbeele et al., 2011b). Finally, the bacteria have to be resistant to antimicrobial peptides. Species of Bacteroides have shown to be resistant to several host defensins allowing their colonization of the outer layer mucus (Nuding et al., 2009). Moreover, it has been suggested that the glycosylation pattern in mucins is an important factor for host selection of a specific colonic mucosal community (Hansson and Johansson, 2010a). Recent study has shown that the glycosylation pattern is complex but relatively conserved in the human colon compared to other regions in the GI tract, hence specific adhesion molecules and mucin‐degrading enzymes are needed suggesting selective advantages of the colonic commensal mucosal community (Larsson et al., 2009).
Theoretical part 9 2. The colonic environment 2.2. The luminal environment The high content and the long transit time of nutrients in the colon allow a sufficient reproduction rate and avoid wash out of the luminal bacteria; hence a high number of bacteria are able to colonize the lumen (10 10 ‐ 10 11 CFU/ ml). These bacteria are either facultative or strict anaerobic and live in mutual relationship with their host helping extract energy by digesting indigestible polysaccharides (Holzapfel et al., 1998;Backhed et al., 2005). The range of indigestible dietary carbohydrates that reaches the colon include polysaccharides from components of plant cell walls (including cellulose, xylan, and pectin), as well as storage polysaccharides such as inulin and resistant starch (Hooper et al., 2002). Recent metagenomic studies have revealed that the microbiome in the human gut is one of the richest sources of carbohydrate active enzymes with at least 81 families of glycoside‐hydrolases (GH) with endo‐ and exo‐activities (Gill et al., 2006;Turnbaugh et al., 2010). Of these families, GH13 (20%), GH3 (11%), GH2 (9%), GH1 (7%), and GH31 (5%) are the most abundant in the gut microbiome of human beings (Gill et al., 2006;Li et al., 2009). The main saccharolytic species in the colon belong to the genera Bacteroides, Bifidobacterium, Ruminococcus, Eubacterium, Lactobacillus, and Clostridium (Vernazza et al., 2006). Bacteroides, the most abundant genus in the colon (section 1.1), has shown to be able to degrade and ferment a wide variety of plant polysaccharides (Hooper et al., 2002). A study by Tasse and colleagues (2010) demonstrated that Bacteroides has genes coding for glycosidic enzymes such as β‐glucanases, xylanases, galactanases, and amylases. Additionally, the study showed that some of the genes coding for the carbohydrate active enzymes in Bacteroides were found in multiple clusters and could be involved in carbohydrate degradation, transport and/or binding. The high saccharolytic capacity of Bacteroides could partly explain why this genus is so abundant in the colon. Bifidobacterium is another dominant genus in the human colon (section 1.1). To this date, nineteen genomes of strains from this genus have been completely sequenced. These include strains of B. adolescentis, B. animalis subsp. lactis, B. angulatum, B. bifidum, B. breve, B. longum subsp. longum, B. longum subsp. infantis, B. pseudocatenulatum, B. catenulatum, and B. gallicum (Pokusaeva et al., 2011). Large numbers of the genes found in the Bifidobacterium genom have shown to encode proteins which are involved in carbohydrate metabolism and transport, such as GH, and sugar ABC transporters (Ventura et al., 2007;Ventura et al., 2010;Pokusaeva et al., 2011).
- 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: 2. The colonic environment Theoreti
- Page 29 and 30: Table 1: The presence of glycoside
- Page 31 and 32: Theoretical part Figure 3: The colo
- Page 33 and 34: 3. Inflammatory Bowel disease Theor
- Page 35 and 36: Theoretical part 17 3. Inflammatory
- 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 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
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- Page 72 and 73: layer of UC patients and found that
- Page 74 and 75: Acknowledgements The authors thank
Theoretical part<br />
9<br />
2. The colonic environment<br />
2.2. The lum<strong>in</strong>al environment<br />
The high content and the long transit time <strong>of</strong> nutrients <strong>in</strong> the colon allow a sufficient reproduction<br />
rate and avoid wash out <strong>of</strong> the lum<strong>in</strong>al bacteria; hence a high number <strong>of</strong> bacteria are able to<br />
colonize the lumen (10 10 ‐ 10 11 CFU/ ml). These bacteria are either facultative or strict anaerobic<br />
and live <strong>in</strong> mutual relationship with their host help<strong>in</strong>g extract energy by digest<strong>in</strong>g <strong>in</strong>digestible<br />
polysaccharides (Holzapfel et al., 1998;Backhed et al., 2005). The range <strong>of</strong> <strong>in</strong>digestible dietary<br />
carbohydrates that reaches the colon <strong>in</strong>clude polysaccharides from components <strong>of</strong> plant cell walls<br />
(<strong>in</strong>clud<strong>in</strong>g cellulose, xylan, and pect<strong>in</strong>), as well as storage polysaccharides such as <strong>in</strong>ul<strong>in</strong> and<br />
resistant starch (Hooper et al., 2002). Recent metagenomic studies have revealed that the<br />
microbiome <strong>in</strong> the human gut is one <strong>of</strong> the richest sources <strong>of</strong> carbohydrate active enzymes with at<br />
least 81 families <strong>of</strong> glycoside‐hydrolases (GH) with endo‐ and exo‐activities (Gill et al.,<br />
2006;Turnbaugh et al., 2010). Of these families, GH13 (20%), GH3 (11%), GH2 (9%), GH1 (7%), and<br />
GH31 (5%) are the most abundant <strong>in</strong> the gut microbiome <strong>of</strong> human be<strong>in</strong>gs (Gill et al., 2006;Li et<br />
al., 2009). The ma<strong>in</strong> saccharolytic species <strong>in</strong> the colon belong to the genera Bacteroides,<br />
Bifidobacterium, Rum<strong>in</strong>ococcus, Eubacterium, Lactobacillus, and Clostridium (Vernazza et al.,<br />
2006).<br />
Bacteroides, the most abundant genus <strong>in</strong> the colon (section 1.1), has shown to be able to degrade<br />
and ferment a wide variety <strong>of</strong> plant polysaccharides (Hooper et al., 2002). A study by Tasse and<br />
colleagues (2010) demonstrated that Bacteroides has genes cod<strong>in</strong>g for glycosidic enzymes such as<br />
β‐glucanases, xylanases, galactanases, and amylases. Additionally, the study showed that some <strong>of</strong><br />
the genes cod<strong>in</strong>g for the carbohydrate active enzymes <strong>in</strong> Bacteroides were found <strong>in</strong> multiple<br />
clusters and could be <strong>in</strong>volved <strong>in</strong> carbohydrate degradation, transport and/or b<strong>in</strong>d<strong>in</strong>g. The high<br />
saccharolytic capacity <strong>of</strong> Bacteroides could partly expla<strong>in</strong> why this genus is so abundant <strong>in</strong> the<br />
colon.<br />
Bifidobacterium is another dom<strong>in</strong>ant genus <strong>in</strong> the human colon (section 1.1). To this date,<br />
n<strong>in</strong>eteen genomes <strong>of</strong> stra<strong>in</strong>s from this genus have been completely sequenced. These <strong>in</strong>clude<br />
stra<strong>in</strong>s <strong>of</strong> B. adolescentis, B. animalis subsp. lactis, B. angulatum, B. bifidum, B. breve, B. longum<br />
subsp. longum, B. longum subsp. <strong>in</strong>fantis, B. pseudocatenulatum, B. catenulatum, and B. gallicum<br />
(Pokusaeva et al., 2011). Large numbers <strong>of</strong> the genes found <strong>in</strong> the Bifidobacterium genom have<br />
shown to encode prote<strong>in</strong>s which are <strong>in</strong>volved <strong>in</strong> carbohydrate metabolism and transport, such as<br />
GH, and sugar ABC transporters (Ventura et al., 2007;Ventura et al., 2010;Pokusaeva et al., 2011).