Role of Intestinal Microbiota in Ulcerative Colitis
Role of Intestinal Microbiota in Ulcerative Colitis Role of Intestinal Microbiota in Ulcerative Colitis
Introduction and objectives Introduction and objectives Since the beginning of the last century from the early work of Elie Metchnikoff, it is believed that a synergistic interaction exists between intestinal microbes and their host. Metchnikoff observed that: “… different susceptibilities of people to the harmful action of microbes and their products. Some can swallow without any evil result a quantity of microbes which in the case of other individuals would produce a fatal attack of cholera. Everything depends upon the resistance offered to the microbes by the invaded organism" (Metchnikoff, 1908). Hence, an unfavorable composition of the gut microbiota could play a role in intestinal infections and diseases. Consumption of indigestible carbohydrates or dietary fibers is suggested to improve gut health by modulating the gut environment through selective stimulation of bacteria who are able to promote beneficial events in the host by inhibition of pathogenic bacteria, and induction of immune regulatory functions (Vernazza et al., 2006). The objectives of this thesis were to investigate, if the gut microbiota and its ability to colonize mucus are different in patients suffering from the intestinal bowel disease, ulcerative colitis (UC) than in healthy subjects, hence playing a role in colonic inflammation. Additionally, investigate the ability of novel indigestible carbohydrates or fibers from sugar beet and potato pulp to induce beneficial changes in fecal microbiota communities in vitro obtained from human volunteers both healthy and UC patients. The first part of this thesis gives a theoretical introduction to the phylogenetic composition of the human intestinal microbiota, the location of the microbiota within the colon and their interactions with the host. Additionally, UC and the colonic microbiota composition observed in UC patients will be described. Finally, modulation of the intestinal microbiota by prebiotics will be addressed together with a description of the production of prebiotics and novel carbohydrates. The second part contains a description of the methodologies used in the studies of this thesis and six papers that demonstrate the experimental work. The last part is discussion and conclusion based on the theoretical and experimental work of this thesis. X
List of manuscripts Paper 1 List of Manuscripts Vigsnæs, L.K., Brynskov, J., Wilcks, A., and Licht, T.R. Gram‐negative bacteria account for differences in fecal microbiota between patients with ulcerative colitis and healthy controls. (2011) Submitted to BMC Microbiology, under review. Paper 2 Vigsnaes, L.K., Van den Abbeele, P., Van de Wiele, T. and Licht, T.R. Fecal lactobacilli, and bifidobacteria from ulcerative colitis patients display reduced ability to colonize mucus in the M‐ SHIME. (2011) Paper in preparation. Paper 3 Vigsnæs, L.K., Holck, J., Meyer, A.S, and Licht, T.R. (2011) In vitro Fermentation of Sugar Beet Arabino‐Oligosaccharides by Fecal Microbiota Obtained from Patients with Ulcerative Colitis Selectively Stimulates the Growth of Bifidobacterium spp. and Lactobacillus spp. Applied and Environmental Microbiology. 77:8336‐8344 Paper 4 Holck, J., Lorentzen, A., Vigsnæs, L.K., Licht, T.R, Mikkelsen, J.D. and Meyer, A.S. (2011) Feruloylated and non‐feruloylated arabino‐oligosaccharides from sugar beet pectin selectively stimulates the growth of Bifidobacterium spp. in human fecal in vitro fermentation. Journal of Agricultural and Food Chemistry. 59:6511‐6519. Paper 5 Thomassen, L.V., Vigsnæs, L.K., Licht, T.R., Mikkelsen, J.D., and Meyer, A.S. (2011) Maximal release of highly bifidogenic soluble dietary fibers from industrial potato pulp by minimal enzymatic treatment. Applied Microbiology and Biotechnology. 90:873‐884. Paper 6 Holck, J., Hjernø, K., Lorentzen, A., Vigsnæs, L.K., Hemmingsen.L., Licht, T.R., Mikkelsen, J.D., Meyer, A.S. (2011) Tailored enzymatic production of oligosaccharides from sugar beet pectin and evidence of differential effects of a single DP chain length difference human fecal microbiota composition after in vitro fermentation. Process Biochemistry. 46 :1039‐1049. XI
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- Page 6 and 7: Preface Preface This thesis present
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Introduction and objectives<br />
Introduction and objectives<br />
S<strong>in</strong>ce the beg<strong>in</strong>n<strong>in</strong>g <strong>of</strong> the last century from the early work <strong>of</strong> Elie Metchnik<strong>of</strong>f, it is believed that a<br />
synergistic <strong>in</strong>teraction exists between <strong>in</strong>test<strong>in</strong>al microbes and their host.<br />
Metchnik<strong>of</strong>f observed that:<br />
“… different susceptibilities <strong>of</strong> people to the harmful action <strong>of</strong> microbes and their products. Some<br />
can swallow without any evil result a quantity <strong>of</strong> microbes which <strong>in</strong> the case <strong>of</strong> other <strong>in</strong>dividuals<br />
would produce a fatal attack <strong>of</strong> cholera. Everyth<strong>in</strong>g depends upon the resistance <strong>of</strong>fered to the<br />
microbes by the <strong>in</strong>vaded organism" (Metchnik<strong>of</strong>f, 1908).<br />
Hence, an unfavorable composition <strong>of</strong> the gut microbiota could play a role <strong>in</strong> <strong>in</strong>test<strong>in</strong>al <strong>in</strong>fections<br />
and diseases. Consumption <strong>of</strong> <strong>in</strong>digestible carbohydrates or dietary fibers is suggested to improve<br />
gut health by modulat<strong>in</strong>g the gut environment through selective stimulation <strong>of</strong> bacteria who are<br />
able to promote beneficial events <strong>in</strong> the host by <strong>in</strong>hibition <strong>of</strong> pathogenic bacteria, and <strong>in</strong>duction <strong>of</strong><br />
immune regulatory functions (Vernazza et al., 2006).<br />
The objectives <strong>of</strong> this thesis were to <strong>in</strong>vestigate, if the gut microbiota and its ability to colonize<br />
mucus are different <strong>in</strong> patients suffer<strong>in</strong>g from the <strong>in</strong>test<strong>in</strong>al bowel disease, ulcerative colitis (UC)<br />
than <strong>in</strong> healthy subjects, hence play<strong>in</strong>g a role <strong>in</strong> colonic <strong>in</strong>flammation. Additionally, <strong>in</strong>vestigate the<br />
ability <strong>of</strong> novel <strong>in</strong>digestible carbohydrates or fibers from sugar beet and potato pulp to <strong>in</strong>duce<br />
beneficial changes <strong>in</strong> fecal microbiota communities <strong>in</strong> vitro obta<strong>in</strong>ed from human volunteers both<br />
healthy and UC patients.<br />
The first part <strong>of</strong> this thesis gives a theoretical <strong>in</strong>troduction to the phylogenetic composition <strong>of</strong> the<br />
human <strong>in</strong>test<strong>in</strong>al microbiota, the location <strong>of</strong> the microbiota with<strong>in</strong> the colon and their <strong>in</strong>teractions<br />
with the host. Additionally, UC and the colonic microbiota composition observed <strong>in</strong> UC patients<br />
will be described. F<strong>in</strong>ally, modulation <strong>of</strong> the <strong>in</strong>test<strong>in</strong>al microbiota by prebiotics will be addressed<br />
together with a description <strong>of</strong> the production <strong>of</strong> prebiotics and novel carbohydrates. The second<br />
part conta<strong>in</strong>s a description <strong>of</strong> the methodologies used <strong>in</strong> the studies <strong>of</strong> this thesis and six papers<br />
that demonstrate the experimental work. The last part is discussion and conclusion based on the<br />
theoretical and experimental work <strong>of</strong> this thesis.<br />
X