P020 Characterisation of mucus in patients with Crohn’s disease

verfasst von

C Kramer, J Ziegler, N Alzain, S Schroeter, A Almalla, L Elomaa, A Addante, A Kuppe, K Fentker, J Nazat Martinez Medina, V H Jarquin-Diaz, H Rulff, M Gradzielski, S Forslund, P Mertins, M Mall, M Weinhart, R Glauben, B Siegmund

Abstract

Background
Crohn’s disease (CD) is a chronic inflammatory condition that can affect all parts of the intestine. Commonly, there is inflammation in the terminal ileum. An intestinal barrier consisting of epithelial cells covered by a mucus layer is on the one hand preventing pathogen invasion while on the other hand allowing the uptake of nutrients. However, despite the significance of the terminal ileum in CD, little is known about the mucus composition and viscoelastic properties in the terminal ileum.
In our study, we wanted to do a comprehensive analysis of the mucus in the terminal ileum of CD patients compared to healthy controls. Thus, we aspire to gain a better understanding of the role of mucus and biophysical and biochemical triggers contained in the mucus layer during the course of ileal inflammation.
Methods
During colonoscopy, native mucus and saline washes containing mucus as well as biopsies from the terminal ileum of 33 CD patients and 25 healthy controls were collected. The disease course and dietary habits of all patients and healthy controls were recorded. Samples were treated according to protocol for different types of analysis such as rheology, proteomics, metabolomics, and microbiome. Furthermore, human intestinal organoids were generated from the biopsies. Additionally, we analysed bulk RNA sequencing data from intestinal mucosal biopsies of a cohort of 128 patients, consisting of non-IBD individuals and CD patients.
Results
We here present preliminary data for the different types of analyses. Regarding the viscoelastic properties, preliminary rheology data suggests that there is no major difference between CD patients and healthy controls. As for proteomics, the first cohort is currently being analysed. Concerning the microbiome, we could show that saline washes containing mucus are more suitable than biopsies for analysing bacterial as well as host DNA. Although not statistically significant, healthy controls showed a tendency for higher alpha- diversity in microbiota. Also there were some differences in the taxonomy. Intestinal organoids were grown as cultures. In the end, the results of the analyses mentioned above will be interpreted together with the clinical data. Concerning the gene expression, we found that 12 mucin and mucin-like genes were expressed both in colon and ileum tissue. Interestingly, a subset of CD patients showed a de-novo expression of MUC5AC, MUC6, MUCL1 and MUCL3 in the ileum.
Conclusion
All in all, in our multidisciplinary study we hope to achieve a thorough analysis of the mucus layer in the terminal ileum, thus gaining new insight into the pathogenetic mechanisms in intestinal inflammation that could prospectively be used for therapeutic means.

Externe Organisation(en)

Charité - Universitätsmedizin Berlin
Freie Universität Berlin (FU Berlin)
Max-Delbrück-Centrum für Molekulare Medizin (MDC) in der Helmholtz-Gemeinschaft
Technische Universität Berlin

Typ

Artikel

Journal

Journal of Crohn's and Colitis

Seiten

i190-i191

ISSN

1873-9946

Publikationsdatum

02.2023

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1093/ecco-jcc/jjac190.0150 (Zugang: Unbekannt)