P0852 Influence of a gluten-free dietary intervention on the gut microbiome and inflammation in inflammatory bowel disease: results from murine experiments and protocol of a prospective proof-of-concept human study as part of the miGut-Health project
Authors: Hübener S , Stallbaum F , Machicote A , Steglich B , Oguz-Coeloglu Z , Jagemann B , Schramm C , Huber S 
Published: January 2025

Abstract

Background
A significant number of inflammatory bowel disease (IBD) patients report an improvement of gastrointestinal symptoms under a gluten-free diet (GFD), despite not suffering from celiac disease. In a recent prospective pilot study, we detected a significant downregulation of proinflammatory cytokines and chemokines on the mucosal level, as well as slight compositional changes of the luminal microbiome after implementation of an eight-week GFD intervention in PSC-IBD patients (1). For a further characterization, we established murine models of IBD, investigating the influence of a GFD on colitis susceptibility, gut microbiota, and intestinal inflammation (Part A). Subsequently, a proof-of-concept human study was implemented as part of the miGut Health project for clinical correlation (Part B).

Methods
A) C57BL/6 mice are either bred and kept under standard diet (SD, containing wheat) or GFD followed by induction of dextran sodium sulfate (DSS) colitis, a murine model for ulcerative colitis. Relative loss of bodyweight and mean endoscopic colitis score are measured. For characterization of the microbiota impact, murine stool transplantation into germ free mice and 16s RNA analyzes are performed.
B) An investigator-initiated prospective clinical trial with one interventional arm in IBD patients will be performed at the University Medical Center Hamburg-Eppendorf to investigate a 1.5-year long wheat protein-free diet in patients with inflammatory bowel disease (IBD) including ulcerative colitis (UC), Crohn’s disease (CD) and PSC-associated IBD (PSC-IBD), n=20 each. Effects of the GFD on intestinal cell composition and state, intestinal fecal and mucosal microbiota composition will be assessed as well as the dietary impact on IBD activity using colonoscopy and biomarkers of intestinal inflammation and on symptoms and health-related quality of life.

Results
A) Gluten aggravates murine DSS-colitis and long-term GFD (LT-GFD) protects mice from gluten aggravated colitis susceptibility. More importantly, preliminary data in germ-free settings support that this effect is mediated through microbiota alterations during the LT-GFD. 16s RNA sequencing data from murine stool showed different relative bacterial abundance.
B) The study protocol received formal ethical approval by the ethics committee of the Hamburg Medical Association, Hamburg, Germany. Patient recruitment has started and is ongoing.

Conclusion
These primary results underline a potential role of gut microbiota modulation for the positive effect of a GFD on gastrointestinal symptoms in IBD. Long-term tolerability and efficacy of the dietary intervention in IBD patients remain to be seen.

References
1.Liwinski T, Hübener S, Henze L, et al. A prospective pilot study of a gluten-free diet for primary sclerosing cholangitis and associated colitis. Aliment Pharmacol Ther. 2023;57(2):224-236. doi:10.1111/apt.17256