Higher prevalence of<i>Bacteroides fragilis</i>in Crohn’s disease exacerbations and strain-dependent increase of epithelial resistance

Becker, Heike E. F.; Jamin, Casper; Bervoets, Liene; Xu, Pan; Pierik, Marie J.; Stassen, Frank R. M.; Penders, John; Jonkers, Daisy

doi:10.1101/2020.05.16.099358

Cited by 2 publications

(2 citation statements)

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“…Faecal metagenomic DNA was isolated as published earlier 28 . Amplicon library preparation and sequencing was conducted as described previously 29 .…”

Section: Methodsmentioning

confidence: 99%

Higher in vitro mucin degradation, but no increased paracellular permeability by faecal water from Crohn’s disease patients

Becker

Kameli

Rustichelli

et al. 2022

Preprint

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Background: Crohn's disease (CD) is a chronic inflammatory gastro-intestinal condition with variable disease course. Impaired barrier function and microbial dysbiosis are associated with disease onset and exacerbations. We hypothesized that perturbed microbial activity may contribute to the impaired barrier function in CD. Therefore, this study aimed to examine the impact of faecal bacterial products of active and remissive CD patients, and healthy controls (HC) on mucin degradation and epithelial barrier function in vitro. Methods: Six HC and twelve CD patients were included. Disease activity was determined by endoscopy. Fecal water (FW) and bacterial membrane vesicles (MVs) from fresh fecal samples were applied on mucin agar to determine mucin degradation and on differentiated Caco-2 cell monolayers to assess transepithelial electrical resistance (TEER) and paracellular junction stability. Relative abundances of fecal bacterial genera, which may be associated mucin degradation, were evaluated using 16S rRNA gene amplicon sequencing. Results: FW-induced mucin degradation was higher in CD samples as compared to HC (p<0.01), but was not linked to specific bacterial relative abundances. FW resulted in 78-87% decrease of TEER in three of the remissive (p<0.001) but not the active CD or HC samples. MVs did not induce mucin degradation or epithelial barrier disruption. Conclusion: The higher mucin degradation capacity of CD-derived FW might indicate contributions of microbial products to CD pathophysiology and warrants further investigation. Moreover, the altered epithelial resistance in some individuals is not due to paracellular disruption.

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“…Faecal metagenomic DNA was isolated as published earlier 28 . Amplicon library preparation and sequencing was conducted as described previously 29 .…”

Section: Methodsmentioning

confidence: 99%

Higher in vitro mucin degradation, but no increased paracellular permeability by faecal water from Crohn’s disease patients

Becker

Kameli

Rustichelli

et al. 2022

Preprint

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“…We would like to thank Prof. Cynthia Sears for kindly providing the B. fragilis strains VPI 13784 and 86-5443-2-2, and the respective deletion mutants. This manuscript has been released as a pre-print at bioRxiv, Becker et al (2020) .…”

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confidence: 99%

Higher Prevalence of Bacteroides fragilis in Crohn’s Disease Exacerbations and Strain-Dependent Increase of Epithelial Resistance

et al. 2021

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Bacteroides fragilis has previously been linked to Crohn’s disease (CD) exacerbations, but results are inconsistent and underlying mechanisms unknown. This study investigates the epidemiology of B. fragilis and its virulence factors bft (enterotoxin) and ubiquitin among 181 CD patients and the impact on the intestinal epithelial barrier in vitro. The prevalence of B. fragilis was significantly higher in active (n = 69/88, 78.4%) as compared to remissive (n = 58/93, 62.4%, p = 0.018) CD patients. Moreover, B. fragilis was associated with intestinal strictures. Interestingly, the intestinal barrier function, as examined by transepithelial electrical resistance (TEER) measurements of Caco-2 monolayers, increased when exposed to secretomes of bft-positive (bft-1 and bft-2 isotype; increased TEER ∼160%, p < 0.001) but not when exposed to bft-negative strains. Whole metagenome sequencing and metabolomics, respectively, identified nine coding sequences and two metabolites that discriminated TEER-increasing from non-TEER-increasing strains. This study revealed a higher B. fragilis prevalence during exacerbation. Surprisingly, bft-positive secretomes increased epithelial resistance, but we excluded Bft as the likely causative factor.

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Higher prevalence ofBacteroides fragilisin Crohn’s disease exacerbations and strain-dependent increase of epithelial resistance

Cited by 2 publications

References 57 publications

Higher in vitro mucin degradation, but no increased paracellular permeability by faecal water from Crohn’s disease patients

Higher in vitro mucin degradation, but no increased paracellular permeability by faecal water from Crohn’s disease patients

Higher Prevalence of Bacteroides fragilis in Crohn’s Disease Exacerbations and Strain-Dependent Increase of Epithelial Resistance

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