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Role of Intestinal Microbiota in Ulcerative Colitis

Role of Intestinal Microbiota in Ulcerative Colitis

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<strong>in</strong>dicates that a change <strong>in</strong> the microbiota from ‘healthy’ to ‘unhealthy’ occurs dur<strong>in</strong>g the remission<br />

period.<br />

Background<br />

<strong>Ulcerative</strong> colitis (UC) is an idiopathic <strong>in</strong>flammatory bowel disease (IBD) which is characterized by<br />

chronic <strong>in</strong>flammation <strong>of</strong> the colonic mucosa. UC is usually associated with recurrent attacks and<br />

complete remission <strong>of</strong> symptoms <strong>in</strong> the <strong>in</strong>terim. The classical symptoms <strong>of</strong> patients <strong>in</strong> relapse are<br />

diarrhea with passage <strong>of</strong> blood or mucus, or both, occasional abdom<strong>in</strong>al cramp<strong>in</strong>g and pa<strong>in</strong> as well<br />

as systemic symptoms such as fever and weight loss <strong>in</strong> severe cases [2,13].<br />

The aetiology <strong>of</strong> <strong>in</strong>flammatory bowel disease rema<strong>in</strong>s an enigma, and no known <strong>in</strong>fectious agent<br />

has yet been demonstrated [30,44]. However, the <strong>in</strong>test<strong>in</strong>al microbiota seems to be <strong>in</strong>volved <strong>in</strong><br />

trigger<strong>in</strong>g <strong>in</strong>flammation, as observed <strong>in</strong> several animal models, where colitis could not be <strong>in</strong>duced<br />

<strong>in</strong> the absence <strong>of</strong> a microbiota [45]. Hence, the <strong>in</strong>test<strong>in</strong>al microbes may <strong>in</strong>fluence some <strong>of</strong> the key<br />

mechanisms that are <strong>in</strong>volved <strong>in</strong> the <strong>in</strong>flammatory processes <strong>of</strong> the gut mucosa [20,44].<br />

Lipopolysaccharides (LPS) released by Gram‐ negative bacteria are able to trigger an <strong>in</strong>flammatory<br />

response through the nuclear factor κB (NF‐κB) pathway lead<strong>in</strong>g to over‐expression <strong>of</strong> pro‐<br />

<strong>in</strong>flammatory cytok<strong>in</strong>es [42]. However, certa<strong>in</strong> Gram‐positive bacteria, particularly bifidobacteria<br />

and lactobacilli, have been shown to have a beneficial therapeutic effect <strong>in</strong> <strong>in</strong>flammatory bowel<br />

disease [23,54]. Additionally, <strong>in</strong> vitro studies show that stra<strong>in</strong>s <strong>of</strong> lactobacilli and bifidobacteria do<br />

not possess any <strong>in</strong>tr<strong>in</strong>sic pro‐<strong>in</strong>flammatory characteristics but exert anti‐<strong>in</strong>flammatory actions<br />

such as <strong>in</strong>hibition <strong>of</strong> NF‐κB activation and IL‐8 secretion [16,42]. Both Gram‐negative and Gram‐<br />

positive bacteria may therefore be <strong>in</strong>volved <strong>in</strong> the pathogenesis <strong>of</strong> <strong>in</strong>flammatory bowel disease.<br />

A recent study, <strong>in</strong>clud<strong>in</strong>g a large metagenomic sequenc<strong>in</strong>g approach, has shown that the fecal<br />

microbiota differs between subjects with UC and healthy controls [41]. However, only very few<br />

<strong>in</strong>vestigations [51,52] have so far exam<strong>in</strong>ed if there are differences between the fecal microbiota<br />

from UC patients <strong>in</strong> relapse and <strong>in</strong> remission by quantitative methods.<br />

The aim <strong>of</strong> our study was therefore to compare fecal microbiota derived from healthy controls,<br />

patients with UC <strong>in</strong> remission, and patients with active disease. Additionally, we wanted to<br />

<strong>in</strong>vestigate if the composition <strong>of</strong> Gram‐negative bacteria and Gram‐positive bacteria differed<br />

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