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Role of Intestinal Microbiota in Ulcerative Colitis

Role of Intestinal Microbiota in Ulcerative Colitis

Role of Intestinal Microbiota in Ulcerative Colitis

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Summary<br />

Summary<br />

The microbiota <strong>of</strong> the human <strong>in</strong>test<strong>in</strong>al tract is complex with variable populations <strong>of</strong> bacteria who<br />

are either permanent gut residents (commensal bacteria) or transient <strong>in</strong>habitants <strong>in</strong>troduced from<br />

the environment. The commensal bacteria are believed to be important for human health due to<br />

actions such as protection aga<strong>in</strong>st pathogens, <strong>in</strong>duction <strong>of</strong> immune regulatory functions and<br />

nutrient process<strong>in</strong>g. Hence, the composition <strong>of</strong> commensal bacteria is important to preserve<br />

colonic health.<br />

<strong>Ulcerative</strong> colitis (UC) is an <strong>in</strong>flammatory bowel disease and dysbiosis <strong>in</strong> the composition <strong>of</strong><br />

commensals has been reported, which could affect colonic health. In the experimental part <strong>of</strong> this<br />

thesis, the fecal microbiota derived from UC patients <strong>in</strong> either remission or with active disease and<br />

healthy subjects was quantified us<strong>in</strong>g quantitative Real‐Time PCR (qPCR) to exam<strong>in</strong>e the<br />

microbiota composition. The results demonstrated that the microbiota composition was different<br />

<strong>in</strong> UC patients <strong>in</strong> relapse compared to healthy subjects and the difference could be ascribed Gram‐<br />

negative bacteria, hence <strong>in</strong>dicat<strong>in</strong>g that an altered microbiota composition is associated with<br />

colonic <strong>in</strong>flammation. Additionally, results revealed that the microbiota composition <strong>in</strong> remission<br />

either resembled the composition <strong>in</strong> healthy or <strong>in</strong> relapse, demonstrat<strong>in</strong>g that the microbiota <strong>in</strong><br />

remission is unstable.<br />

The mucus layer l<strong>in</strong><strong>in</strong>g the epithelium <strong>of</strong> the <strong>in</strong>test<strong>in</strong>al tract is important for the protection <strong>of</strong> the<br />

epithelium <strong>in</strong> humans. The commensal bacteria that colonize the colonic mucus are suggested to<br />

play an important role <strong>in</strong> stimulat<strong>in</strong>g regulatory immune responses compared to lum<strong>in</strong>al bacteria,<br />

s<strong>in</strong>ce they reside closer to the <strong>in</strong>test<strong>in</strong>al epithelial cells. The ability <strong>of</strong> fecal microbiota derived<br />

from healthy subjects and UC patients to colonize mucus was exam<strong>in</strong>ed <strong>in</strong> a study <strong>of</strong> this thesis to<br />

elucidate, if the adhesion capacity is different depend<strong>in</strong>g on disease state. For this purpose, an <strong>in</strong><br />

vitro dynamic gut model was used. Several bacterial taxa from both lumen and mucus were<br />

quantified us<strong>in</strong>g qPCR. The results revealed that the bacterial community <strong>of</strong> the mucus differed<br />

from that <strong>of</strong> the lumen and that lactobacilli and bifidobacteria derived from UC patients had a<br />

significant decreased capacity to colonize mucus than observed for similar bacterial groups<br />

orig<strong>in</strong>at<strong>in</strong>g from healthy subjects. This suggests that the <strong>in</strong>flammatory state <strong>in</strong> UC may <strong>in</strong>fluence<br />

the adhesion capacity <strong>of</strong> commensal bacteria such as beneficial Gram‐positive bacteria lactobacilli<br />

and bifidobacteria.<br />

VI

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