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bioRxiv · 10.1101/2022.08.26.505386

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

Becker, H. E.·Kameli, N.·Rustichelli, A.·Stassen, F. R.·Penders, J.·Jonkers, D. M.
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Abstract

BackgroundCrohns 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. MethodsSix 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. ResultsFW-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. ConclusionThe 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. Key MessagesWhat is already known? Intestinal microbial dysbiosis and mucosal barrier dysfunction are important contributors to Crohns disease aetiology and disease exacerbations. What is new here? The faecal microbial secretome of Crohns disease patients has a higher mucin degradation capacity as compared to the secretome of healthy subjects. How can this study help patient care? The increased mucin degradation based on the microbial secretome may be a new target for the development of complementary, microbiome-based therapy in Crohns disease. SummaryMicrobial dysbiosis and intestinal barrier dysfunction can impact Crohns disease course. This translational study found higher mucin degradation, but no epithelial barrier disruption, by the faecal microbial secretome of (active) Crohns disease patients, as compared to healthy controls.

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Becker, H. E., Kameli, N., Rustichelli, A., Stassen, F. R., Penders, J., Jonkers, D. M.. 2022-08-26. Higher in vitro mucin degradation, but no increased paracellular permeability by faecal water from Crohn's disease patients. https://doi.org/10.1101/2022.08.26.505386

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