Abstract Background Collagenous colitis (CC) is a form of microscopic colitis (MC) and is characterized by chronic watery diarrhoea and urgency sometimes leading to incontinence resulting in significantly decreased quality of life1. MC is thought to develop due to a pathological immune response to intestinal luminal antigens in genetically predisposed individuals2. Intestinal microbiota is thought to play a key role in the pathogenesis of MC3. However, neither the pathogenesis of MC nor the role of microbiota in its development are fully understood. The aim of our study was to create a mouse model of CC using faecal microbiota transplantation (FMT) in order to gain further insight into the role of gut microbiota in MC pathogenesis. Methods In the model we used C57BL/6 mice (8 weeks old) across seven treatment groups (n = 10/group). This included 2 control groups (one receiving no FMT and one receiving FMT from healthy controls) and 5 groups receiving FMT prepared from different CC donors. The FMT was performed via enema after broad spectrum antibiotic treatment and bowel cleansing. Afterwards the mice received FMT daily via the oral route. The mice were followed up for 24 weeks. Blood analysis and 16S rRNA sequencing of fecal samples were performed at multiple time points. At the end of the experiment, histological analysis of the animals’ digestive tract was performed. Results Significant decreases in alpha diversity (Shannon) and alterations in bacterial composition were observed across all groups after antibiotic treatment. Beta diversity analysis at different timepoints revealed that mouse microbiome composition steadily drifted towards baseline across all groups (figure 1), with donor microbiota accounting for a small fraction (1-2 %) by week 24 across all FMT groups. Throughout the experiment, microbiota changes exhibited significant heterogeneity within groups, with individual differences, rather than FMT, being the primary factor. Immune cell analysis in the blood showed a dynamic pattern: white blood cell and lymphocyte counts declined initially, peaked at 8 weeks, and stabilized by 24 weeks. Granulocyte levels fluctuated markedly, reaching their highest point at 16 weeks, whereas monocyte counts remain stable throughout. Histological analysis revealed no morphological changes of the mice digestive tract across all groups. Conclusion FMT from CC donors failed to induce inflammatory changes in mice. References: 1.Verhaegh BPM, Münch A, Guagnozzi D, Wildt S, Cebula W, Pedersen N, et al. The long-term disease course of microscopic colitis: A European prospective incident cohort study. Journal of Crohn’s and Colitis. 2025 Jul 1;19(7). 2.Miehlke S, Guagnozzi D, Zabana Y, Tontini GE, Fiehn AMK, Wildt S, et al. European guidelines on microscopic colitis: United European Gastroenterology (UEG) and European Microscopic Colitis Group (EMCG) statements and recommendations. United European Gastroenterology Journal. 2020. 3. Burke KE, D’Amato M, Ng SC, Pardi DS, Ludvigsson JF, Khalili H. Microscopic colitis. Nature Reviews Disease Primers. 2021;7(1). Conflict of interest: Mr. Kiudelis, Vytautas: Fnancial support for travelling and educational activities: AbbVie, Takeda, Janssen, Pfizer, Ferring, Dr. Falk Pharma, MSD. Speaker fees: AbbVie, Ferring, Dr. Falk Pharma. Mingaila, Jonas: No conflict of interest Karaliute, Indre: No conflict of interest Alzbutas, Gediminas: No conflict of interest Elabd, Hesham: No conflict of interest Burokas, Aurelijus: No conflict of interest Kiudelis, Gediminas: No conflict of interest Skieceviciene, Jurgita: No conflict of interest Kupčinskas, Juozas: No conflict of interest
Kiudelis et al. (Thu,) studied this question.