Gastroenterology

Gastroenterology

Volume 122, Issue 1, January 2002, Pages 44-54
Gastroenterology

Clinical Research
Mucosal flora in inflammatory bowel disease*

https://doi.org/10.1053/gast.2002.30294Get rights and content

Abstract

Background & Aims: Microorganisms that directly interact with the intestinal mucosa are obscured by fecal flora and poorly characterized. Methods: We investigated the mucosal flora of washed colonoscopic biopsies of 305 patients with bowel inflammation and 40 controls. The microbial cultures were validated by quantitative polymerase chain reaction with subsequent cloning and sequencing, fluorescence in-situ hybridization, and electron microscopy. Results: We found high concentrations of mucosal bacteria in patients with bowel inflammation, but not in controls. The concentrations of mucosal bacteria increased progressively with the severity of disease, both in inflamed and non-inflamed colon. In patients with >10,000 cfu/μL, a thick bacterial band was attached to the intact mucosa without signs of translocation. Patients with inflammatory bowel disease (IBD) and concentrations of mucosal bacteria >50,000 cfu/μL had characteristic inclusions of multiple polymorphic bacteria within solitary enterocytes located next to the lamina propria, without or having no contact with the fecal stream. The identified bacteria were of fecal origin. Conclusions: Our findings suggest that the changes in the mucosal flora in IBD are not secondary to inflammation, but a result of a specific host response. We hypothesize that the healthy mucosa is capable of holding back fecal bacteria and that this function is profoundly disturbed in patients with IBD.

GASTROENTEROLOGY 2002;122:44-54

Section snippets

Patients

The study was approved by the institutional review board, and the patients gave informed consent. Twenty-eight patients with self-limiting colitis, 104 patients with indeterminate colitis, 119 patients with ulcerative colitis (UC), 54 patients with Crohn's disease (CD), and 40 asymptomatic controls with normal colonoscopic findings were studied at the Charité, the University Hospital of the Humboldt University in Berlin. These patients were referred for evaluation and therapy by family

Bacterial concentration

The concentrations of mucosal bacteria were low in asymptomatic controls and high in patients with bowel inflammation, especially in patients with CD (Table 3).The bacterial concentrations in self-limiting and indeterminate colitis were intermediate. The percent of patients with >10,000 cfu/μL was significantly higher in IBD (P < 0.001) than in the other groups. Figure 1 shows the percent of patients with concentrations of mucosal bacteria of <1000, <10,000, <50,000, and >50,000 cfu/μL.

. Percent

Discussion

Using a simple and reliable protocol of biopsy wash followed by hypotonic lysis, we showed that the mucosal surface in healthy controls is basically sterile and that the concentrations of mucosal bacteria increased progressively from self-limiting colitis to indeterminate colitis to IBD, being highest in CD patients.

Similar to previous studies, we found no principal difference in the composition of the mucosal flora in IBD patients and controls.4, 15, 16, 17 Species isolated from the washed

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    *

    Address requests for reprints to: Alexander Swidsinski, M.D., Innere Klinik, Gastroenterologie, Charité, 10098 Berlin, Germany. e-mail: [email protected]; fax: (011) 49 30 450 514 923.

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