AUTHOR=Becker Heike E. F. , Jamin Casper , Bervoets Liene , Boleij Annemarie , Xu Pan , Pierik Marie J. , Stassen Frank R. M. , Savelkoul Paul H. M. , Penders John , Jonkers Daisy M. A. E. 

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.598232

DOI=10.3389/fmicb.2021.598232

ISSN=1664-302X

ABSTRACT=<p><italic>Bacteroides fragilis</italic> has previously been linked to Crohn’s disease (CD) exacerbations, but results are inconsistent and underlying mechanisms unknown. This study investigates the epidemiology of <italic>B. fragilis</italic> and its virulence factors <italic>bft</italic> (enterotoxin) and <italic>ubiquitin</italic> among 181 CD patients and the impact on the intestinal epithelial barrier <italic>in vitro</italic>. The prevalence of <italic>B. fragilis</italic> was significantly higher in active (<italic>n</italic> = 69/88, 78.4%) as compared to remissive (<italic>n</italic> = 58/93, 62.4%, <italic>p</italic> = 0.018) CD patients. Moreover, <italic>B</italic>. <italic>fragilis</italic> 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 <italic>bft</italic>-positive (<italic>bft-1</italic> and <italic>bft-2</italic> isotype; increased TEER ∼160%, <italic>p</italic> &lt; 0.001) but not when exposed to <italic>bft-</italic>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 <italic>B. fragilis</italic> prevalence during exacerbation. Surprisingly, <italic>bft-</italic>positive secretomes increased epithelial resistance, but we excluded Bft as the likely causative factor.</p>