In Vitro Mucin Degradation and Paracellular Permeability by Fecal water from Crohn’s Disease Patients

Abstract

Aim: This study aimed to examine the impact of fecal water (FW) of active and remissive Crohn’s disease (CD) patients on mucin degradation and epithelial barrier function. Methods: FW and bacterial membrane vesicles (MVs) were isolated from fresh fecal samples of six healthy controls (HCs) and 12 CD patients. Bacterial composition was determined by 16S rRNA gene amplicon sequencing. Results: In vitro FW-induced mucin degradation was higher in CD samples versus HC (p < 0.01), but not associated with specific bacterial genera. FW of three remissive samples decreased transepithelial electrical resistance in Caco-2 cells by 78–87% (p < 0.001). MVs did not induce barrier alterations. Conclusion: The higher mucin-degradation capacity of CD-derived FW might suggest contributions of microbial products to CD pathophysiology.

Tweetable abstract

Researchers at the @penderslab have found that fecal water of #CrohnsDisease patients results in mucin degradation and decreased epithelial resistance.

Keywords: :

• Crohn’s disease
• fecal microbial secretome
• intestinal epithelial barrier
• mucin

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/fmb-2022-0265

Author contributions

The study was conceptualized by HEF Becker, F Stassen, DMAE Jonkers and J Penders. Experiments were conducted by HEF Becker, BAM Heijnens, and A Rustichelli and were analyzed by HEF Becker, A Rustichelli and N Kameli. The manuscript was written by HEF Becker and reviewed by all co-authors.

Financial disclosure

This study was supported by the NUTRIM Graduate Program Grant from Maastricht University. DMAE Jonkers received unrelated funding from the Top Knowledge Institute grant, Carbokinetics program as part of NWO-CCC, H2020/nr. 848228 DISCOvERIE. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study protocol was approved by the Medical Ethics Committee of the Maastricht University Medical Centre+ (Maastricht IBS: NL24160.068.08; IBD South Limburg: NL31636.068.10) and registered on www.clinicaltrials.gov (NCT00775060, resp. NCT02130349). All participants gave written informed consent prior to participation. The study was conducted in accordance with the revised Declaration of Helsinki and in compliance with good clinical practice.