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Spatial Organization and Composition of the Mucosal Flora in Patients with Inflammatory Bowel Disease
Open accessAbstract
The composition and spatial organization of the mucosal flora in biopsy specimens from patients with inflammatory bowel disease (IBD; either Crohn's disease or ulcerative colitis), self-limiting colitis, irritable-bowel syndrome (IBS), and healthy controls were investigated by using a broad range of fluorescent bacterial group-specific rRNA-targeted oligonucleotide probes. Each group included 20 subjects. Ten patients who had IBD and who were being treated with antibiotics were also studied. Use of nonaqueous Carnoy fixative to preserve the mucus layer was crucial for detection of bacteria adherent to the mucosal surface (mucosal bacteria). No biofilm was detectable in formalin-fixed biopsy specimens. Mucosal bacteria were found at concentrations greater than 10 9 /ml in 90 to 95% of IBD patients, 95% of patients with self-limiting colitis, 65% of IBS patients, and 35% of healthy controls. The mean density of the mucosal biofilm was 2 powers higher in IBD patients than in patients with IBS or controls, and bacteria were mostly adherent. Bacteroides fragilis was responsible for >60% of the biofilm mass in patients with IBD but for only 30% of the biofilm mass in patients with self-limiting colitis and <15% of the biofilm mass in patients with IBS. In contrast, bacteria which positively hybridized with the probe specific for Eubacterium rectale - Clostridium coccoides accounted for >40% of the biofilm in IBS patients but for <15% of the biofilm in IBD patients. In patients treated with (5-ASA) or antibiotics, the biofilm could be detected with 4,6-diamidino-2-phenylindole but did not hybridize with fluorescence in situ hybridization probes. A Bacteroides fragilis biofilm is the main feature of IBD. This was not previously recognized due to a lack of appropriate tissue fixation. Both 5-ASA and antibiotics suppress but do not eliminate the adherent biofilm.
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“Spatial niche partitioning of microbial populations can also be a result of mucus from goblet cells 46 and differential oxygen tolerance47.”
From The gut Microbiome in adult and pediatric functional gastrointestinal disorders (2019) · cites this paper as [46]
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ResultGarrett, W. S., Gallini, C. A., Yatsunenko, T., Michaud, M., DuBois, A., Delaney, M. L., Punit, S., Karlsson, M., Bry, L., Glickman, J. N., et al. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.08.004 · Cited by 788
“As has been reported in IBD patients using a universal bacterial 16S rRNA FISH probe (Swidsinski et al., 2005), we observed that the colonic mucus of colitic TRUC mice harbored numerous bacteria and that there was a consistent loss of a ‘‘bacterialfree zone’’ adjacent to the colonic epithelium (Figure 2E).”
MethodInfluentialHost–microbiota interactions in inflammatory bowel disease
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The gut microbiome: connecting spatial organization to function
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InfluentialIntestinal microbiota in human health and disease: the impact of probiotics
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InfluentialWalker, A. W., Sanderson, J. D., Churcher, C. M., Parkes, G. C., Hudspith, B. N., Rayment, N. B., Brostoff, J., Parkhill, J., Dougan, G., & Petrovska, L. (2011) · BMC Microbiology · doi:10.1186/1471-2180-11-7 · Cited by 727
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“…et al., 2005) increased colonization by Enterobacteriaceae (Mylonaki et al., 2005) or the Gamma subdivision of Proteobacteria, Enterobacteriaceae and Bacteroides/ Prevotella (Kleessen et al., 2002), while others describe the presence of a non-invasive Bacteroides biofilm (Swidsinski et al., 2005).”
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Öhman, L., & Simrén, M. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.4 · Cited by 617
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Staley, C. M., Weingarden, A. R., Khoruts, A., & Sadowsky, M. J. (2016) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-016-8006-6 · Cited by 595
“It is well established that the fecal and intestinal mucosal microbiota of human patients with IBD, particularly ileal Crohn's disease, are highly altered compared to healthy individuals (Swidsinski et al. 2005; Frank et al. 2007; Sokol et al. 2008; Willing et al. 2009).”
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Schroeder, B. O. (2019) · Gastroenterology report · doi:10.1093/gastro/goy052 · Cited by 464
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“and a significantly higher proportion of the Proteobacteria phylum.(70,71,73,74) Notably, these differences are present even in patients with Crohn’s disease who are treatment-na€ıve, suggesting that intestinal dysbiosis in these patients is not a consequence of therapy, but rather a potential early change in IBD.”
BackgroundPart 1: The Human Gut Microbiome in Health and Disease.
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“Some Bacteroides species have previously been shown to be present in increased levels in persons suffering from IBD (Gophna et al., 2006; Swidsinski et al., 2005), yet animal models have provided conflicting evidence as to which species may cause CD, warranting closer examination.”
BackgroundInteractions of Intestinal Bacteria with Components of the Intestinal Mucus
Sicard, J.-F., Bihan, G. L., Vogeleer, P., Jacques, M., & Harel, J. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00387 · Cited by 481
Gut Microbiota and Inflammation
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“fragilis have also been linked to inflammatory bowel diseases (IBD) [58–60].”
BackgroundSpecificities of the fecal microbiota in inflammatory bowel disease
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Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum / necrophorum
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“Paraffin-embedded caecal biopsies and faecal cylinders (400 each) that were previously investigated in our clinic for the study of mucosal”
MethodSelf-citationImmune Responses to the Microbiota at the Intestinal Mucosal Surface
Duerkop, B. A., Vaishnava, S., & Hooper, L. V. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.009 · Cited by 424
“For example, IBD patients exhibit increased numbers of mucosal surface-associated bacteria (Swidsinski et al., 2005), suggesting a failure of mechanisms that normally sequester microbiota from direct contact with the surface epithelium.”
BackgroundProbiotic Lactobacillus reuteri biofilms produce antimicrobial and anti-inflammatory factors
Jones, S. E., & Versalovic, J. A. (2009) · BMC Microbiology · doi:10.1186/1471-2180-9-35 · Cited by 417
“Using non-aqueous fixatives and special techniques, several groups have documented the presence of intestinal biofilms in the mammalian intestine [14-17].”
BackgroundEnterotoxigenic Bacteroides fragilis : a Rogue among Symbiotes
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“The histology of ETBF disease in animals has not identified adherent organisms, but available results are limited by formalin fixation, which can interfere with detection of mucosal adherence in the colon (111).”
BackgroundMénage à trois in the human gut: interactions between host, bacteria and phages
Mirzaei, M. K., & Maurice, C. F. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.30 · Cited by 420
Precision Nutrition and the Microbiome, Part I: Current State of the Science
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“densities of mucosa-associated bacteria were reported in IBD patients [64, 65, 70], and were suspected to play a”
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“Reduction in Eubacterium is associated with increased incidence of Crohn’s disease [141] while increased presence is associated with both irritable bowel syndrome [142] and inflammatory bowel disease [143].”
BackgroundHold, G. L. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i5.1192 · Cited by 365
Comparative study of the intestinal mucus barrier in normal and inflamed colon
Swidsinski, A. V., Loening-Baucke, V. A., Theissig, F., Engelhardt, H., Bengmark, S., Koch, S., Lochs, H. H., & Dörffel, Y. (2006) · Gut · doi:10.1136/gut.2006.098160 · Cited by 365
Self-citationInteractions between Intestinal Microbiota and Host Immune Response in Inflammatory Bowel Disease
Zhang, M., Sun, K., Wu, Y., Yang, Y., Tso, P., & Wu, Z. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00942 · Cited by 347
“demonstrated increased bacterial adherence to the mucosal surface of IBD patients, indicating a decreased ability to limit direct contact between the epithelium and intestinal microbiota and the potential over-activation of the host immune response (83) (Figure 2).”
BackgroundPhylogenetic Analysis of Dysbiosis in Ulcerative Colitis During Remission
Rajilić-Stojanović, M. D., Shanahan, F., Guarner, F., & de Vos, W. M. (2013) · Inflammatory Bowel Diseases · doi:10.1097/mib.0b013e31827fec6d · Cited by 360
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“In comparison, a range of 13–35% of healthy screening colonoscopy patients have been reported to harbor colonic biofilms, with equivalent percentages of biofilms on the right and left sides.(16,23) Notably, the prevalence of biofilms in the healthy biopsies in the present meta-analysis was lower than expected (6%); ho…”
MethodResultMetabolism Links Bacterial Biofilms and Colon Carcinogenesis
Johnson, C. H., Dejea, C. M., Edler, D., Hoang, L. T., Santidrián, A. F., Felding, B. H., Ivanišević, J., Cho, K., Wick, E. C., Hechenbleikner, E. M., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.04.011 · Cited by 355
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BackgroundHeimesaat, M. M., Bereswill, S., Fischer, A., Fuchs, D., Struck, D., Niebergall, J., Jahn, H.-K., Dunay, I. R., Moter, A., Gescher, D. M., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.12.8785 · Cited by 345
“Intestinal bacteria trigger large bowel inflammation in IBD (2–7) and graft-vs-host disease (GvHD) after bone marrow transplantation (8, 9).”
BackgroundInfluentialSwidsinski, A. V., Mendling, W., Loening-Baucke, V. A., Swidsinski, S., Dörffel, Y., Scholze, J., Lochs, H. H., & Verstraelen, H. (2007) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2007.06.039 · Cited by 337
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Gut microbiota role in irritable bowel syndrome: New therapeutic strategies
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Role of the microbiota in inflammatory bowel diseases
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Antimicrobial Defense of the Intestine
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“Indeed, patients with inflammatory bowel disease exhibit increased numbers of microbes associated with the gut mucosa [45–49], and innate immune defects have been shown to exist in patients with Crohn’s disease [50].”
Mucins and Their Role in Shaping the Functions of Mucus Barriers
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“In health, mucus appears to play an important role in suppressing virulence of these opportunistic pathogens and in promoting their coexistence as part of a stable microbiota (Swidsinski et al. 2005).”
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The intestinal microbiota and chronic disorders of the gut
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“Patients with IBD were shown to have twice the concentration of mucosal Bacteroides fragilis biofilm compared with controls, the concentration of which was modified by antimicrobial therapy”
BackgroundBacArena: Individual-based metabolic modeling of heterogeneous microbes in complex communities
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Commensal and Pathogenic Escherichia coli Metabolism in the Gut
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The Genotypic View of Social Interactions in Microbial Communities
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Interplay Between Exercise and Gut Microbiome in the Context of Human Health and Performance
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Role of antibiotics for treatment of inflammatory bowel disease
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Cultivable bacterial diversity from the human colon
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“Bacteroides spp. may also be particularly dominant in mucosal biofilms from ulcerative colitis patients (Swidsinski et al. 2005).”
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Gastrointestinal biofilms in health and disease
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“Data inappropriate for analysis (n = 4) [20, 21, 22, 23] Animal experiments excluded (n = 21)”
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“A fluorescence in situ hybridization (FISH) study showed unsubtyped IBS patients to harbour slightly more total bacteria and significantly more members of Clostridium cluster XIVa than the HCs (Swidsinski et al., 2005).”
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Metadata
- Authors
- Swidsinski, A., Weber, J., Loening-Baucke, V., Hale, L. P., & Lochs, H.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Duke Medical Center (US)
- Venue
- Journal of Clinical Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2005-07
- Volume
- 43
- Issue
- 7
- Pages
- 3380-3389
- ISSN
- 0095-1137 (ISSN-L)
- 1098-660X
- PMC
- PMC1169142
- OpenAlex
- W2097177097
- Cited by
- 894
- References
- 36
- Citations by year
- 2026: 15 · 2025: 27 · 2024: 45 · 2023: 47 · 2022: 59 · 2021: 47 · 2020: 50 · 2019: 54 · 2018: 46 · 2017: 35 · 2016: 47 · 2015: 49 · 2014: 41 · 2013: 43 · 2012: 44
- FWCI
- 12.71
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Clinical Microbiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli and Edythe Broad Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Health Sciences › Medicine › Gastroenterology › Microscopic Colitis
- Keywords
- inflammatory bowel disease, Crohn's disease, ulcerative colitis, Bacteroides fragilis, irritable bowel syndrome, 5-aminosalicylic acid, antibiotic therapy, bacterial adhesion, fluorescence in situ hybridization, rRNA-targeted oligonucleotide probes
- MeSH terms
- Adult, Bacteria, Bacteroides fragilis, Biopsy, Colitis, Ulcerative, Crohn Disease, Female, Humans, Intestinal Mucosa, Male, Middle Aged, Colon, Sigmoid, In Situ Hybridization, Fluorescence, Ecosystem, Biofilms
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