Role of Intestinal Microbiota in Ulcerative Colitis
Role of Intestinal Microbiota in Ulcerative Colitis Role of Intestinal Microbiota in Ulcerative Colitis
Summary Summary The microbiota of the human intestinal tract is complex with variable populations of bacteria who are either permanent gut residents (commensal bacteria) or transient inhabitants introduced from the environment. The commensal bacteria are believed to be important for human health due to actions such as protection against pathogens, induction of immune regulatory functions and nutrient processing. Hence, the composition of commensal bacteria is important to preserve colonic health. Ulcerative colitis (UC) is an inflammatory bowel disease and dysbiosis in the composition of commensals has been reported, which could affect colonic health. In the experimental part of this thesis, the fecal microbiota derived from UC patients in either remission or with active disease and healthy subjects was quantified using quantitative Real‐Time PCR (qPCR) to examine the microbiota composition. The results demonstrated that the microbiota composition was different in UC patients in relapse compared to healthy subjects and the difference could be ascribed Gram‐ negative bacteria, hence indicating that an altered microbiota composition is associated with colonic inflammation. Additionally, results revealed that the microbiota composition in remission either resembled the composition in healthy or in relapse, demonstrating that the microbiota in remission is unstable. The mucus layer lining the epithelium of the intestinal tract is important for the protection of the epithelium in humans. The commensal bacteria that colonize the colonic mucus are suggested to play an important role in stimulating regulatory immune responses compared to luminal bacteria, since they reside closer to the intestinal epithelial cells. The ability of fecal microbiota derived from healthy subjects and UC patients to colonize mucus was examined in a study of this thesis to elucidate, if the adhesion capacity is different depending on disease state. For this purpose, an in vitro dynamic gut model was used. Several bacterial taxa from both lumen and mucus were quantified using qPCR. The results revealed that the bacterial community of the mucus differed from that of the lumen and that lactobacilli and bifidobacteria derived from UC patients had a significant decreased capacity to colonize mucus than observed for similar bacterial groups originating from healthy subjects. This suggests that the inflammatory state in UC may influence the adhesion capacity of commensal bacteria such as beneficial Gram‐positive bacteria lactobacilli and bifidobacteria. VI
Summary Maintenance of a benign gut microbial composition may help decrease risk of mucosal inflammation in UC. This could be achieved by the consumption of prebiotics (include non‐ digestible carbohydrates), which are defined as “selectively fermented ingredients that cause specific changes in composition and/or activity in the gastointestinal microbiota, which confer benefits upon host well‐being and health.” In the experimental part of this thesis, in vitro fermentation studies were performed using fecal samples from human volunteers either healthy and/or UC patients to investigate prebiotic properties of novel carbohydrate preparations. The results revealed that incubation with arabino‐ oligosaccharides (DP2‐10) from sugar beet pulp could selectively stimulate fecal lactobacilli and bifidobacteria from UC patients. This may suggest protective properties of arabino‐ oligosaccharides against UC. In addition, in vitro fermentation studies demonstrated that high molecular weight fractions of galactose or arabinose chains either from potato or sugar beet pulp, respectively, selectively stimulated the growth of fecal bifidobacteria derived from healthy subjects. The prebiotic properties demonstrated by the high molecular weight carbohydrate preparations in vitro could be of importance in vivo, since long‐chain carbohydrates may be fermented slowly by beneficial colonic bacteria, thus penetrating prebiotic effect all the way throughout the colon. VII
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- Page 6 and 7: Preface Preface This thesis present
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- Page 12 and 13: Introduction and objectives Introdu
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- Page 25 and 26: 2. The colonic environment Theoreti
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Summary<br />
Ma<strong>in</strong>tenance <strong>of</strong> a benign gut microbial composition may help decrease risk <strong>of</strong> mucosal<br />
<strong>in</strong>flammation <strong>in</strong> UC. This could be achieved by the consumption <strong>of</strong> prebiotics (<strong>in</strong>clude non‐<br />
digestible carbohydrates), which are def<strong>in</strong>ed as “selectively fermented <strong>in</strong>gredients that cause<br />
specific changes <strong>in</strong> composition and/or activity <strong>in</strong> the gasto<strong>in</strong>test<strong>in</strong>al microbiota, which confer<br />
benefits upon host well‐be<strong>in</strong>g and health.”<br />
In the experimental part <strong>of</strong> this thesis, <strong>in</strong> vitro fermentation studies were performed us<strong>in</strong>g fecal<br />
samples from human volunteers either healthy and/or UC patients to <strong>in</strong>vestigate prebiotic<br />
properties <strong>of</strong> novel carbohydrate preparations. The results revealed that <strong>in</strong>cubation with arab<strong>in</strong>o‐<br />
oligosaccharides (DP2‐10) from sugar beet pulp could selectively stimulate fecal lactobacilli and<br />
bifidobacteria from UC patients. This may suggest protective properties <strong>of</strong> arab<strong>in</strong>o‐<br />
oligosaccharides aga<strong>in</strong>st UC. In addition, <strong>in</strong> vitro fermentation studies demonstrated that high<br />
molecular weight fractions <strong>of</strong> galactose or arab<strong>in</strong>ose cha<strong>in</strong>s either from potato or sugar beet pulp,<br />
respectively, selectively stimulated the growth <strong>of</strong> fecal bifidobacteria derived from healthy<br />
subjects. The prebiotic properties demonstrated by the high molecular weight carbohydrate<br />
preparations <strong>in</strong> vitro could be <strong>of</strong> importance <strong>in</strong> vivo, s<strong>in</strong>ce long‐cha<strong>in</strong> carbohydrates may be<br />
fermented slowly by beneficial colonic bacteria, thus penetrat<strong>in</strong>g prebiotic effect all the way<br />
throughout the colon.<br />
VII
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