What question did this study set out to answer?

This study aims to investigate the impact of diet and fecal microbiota transplantation on disease activity in a humanized model of ulcerative colitis.

January 23, 2026

P0146Mediterranean Diet Improves Disease Activity and Microbial Diversity, While Donor-Dependent FMT Independently Reduces Disease Activity in Humanized UC Mice

Key Points

This study aims to investigate the impact of diet and fecal microbiota transplantation on disease activity in a humanized model of ulcerative colitis.
Utilized female C57BL/6 mice humanized with UC-derived microbiota.
Administered broad-spectrum antibiotics followed by different diets: Mediterranean, Western, and Control.
Performed multiple single-donor and multidonor fecal microbiota transplantations (FMT).
Induced colitis with DSS and evaluated disease activity indices, fecal samples for 16S sequencing, and collected tissues for histological analysis.
The Mediterranean diet improved disease activity; the Western diet worsened it.
FMT effectiveness was donor-dependent, with the best outcomes from Donor 1 across diets.
Antibiotic treatment decreased alpha diversity, restored by humanization and Mediterranean diet introduction.
After treatment, the Mediterranean diet significantly increased alpha diversity compared to other dietary groups.

Abstract

Abstract Background Fecal microbiota transplantation (FMT) has been shown to be a promising approach to treat active ulcerative colitis (UC), and donor effects have been observed. Both single- and multidonor FMTs have been used, but with ambiguous results. Also, diet plays a crucial role in shaping the gut microbiome and might affect the efficacy of FMT. Therefore, we aimed to investigate the role of diet and different single-donor and their mixture as multidonor formulations in FMT efficacy exploiting a humanized IBD model. Methods Female C57BL/6 mice (8-11w) were treated with broad-spectrum antibiotics followed by humanization with either UC single-donor patient-derived microbiota, and subsequently randomized to either Western, Mediterranean or Control diet in combination with three distinct healthy single-donor FMT, a combination of these donors in a multidonor FMT or sham (n = 4/grp; Fig1A). After one week, mice were subjected to DSS to induce acute colitis (7d, 2.5%), followed by another 7d of recovery. Disease activity indices (DAI) were determined and evaluated by area under the curve (AUC). Feces were collected for 16S sequencing on day 6, 16 and 30. At sacrifice, blood and different tissues collected for histology, and RNA sequencing. Results Differences in disease activity can be observed and are initiated after introduction of DSS on day 16 (Fig. 1B-C, Table 1). Independent from FMT, Mediterranean diet was shown to improve disease, whereas a Western diet worsened disease outcomes (Fig. 1D, both p 0.05). Independently from diet, FMT seemed to improve disease and to be donor-dependent (Fig. 1E, p 0.05). The effect of FMT donor on DAI was not significantly influenced by dietary background (ANOVA, p = 0.65). Donor 1 consistently showed the best outcomes across all diets, whereas donors 2, 3, and the multi-donor approach exhibited variable results that depended on the specific dietary background. Antibiotic treatment significantly reduced alpha diversity (p 0.01), which was restored after humanization and dietary introduction. After DSS treatment and recovery (day 30), animals on a Mediterranean diet had significantly higher alpha diversity given by observed richness (p 0.01; Fig. 1F) compared to those on control and Western diets as well as compared to those not receiving DSS (healthy controls). Nevertheless, no differences were observed in terms of FMT origin (p = 0.91). Histology and RNA sequencing results are in process. Conclusion Both Mediterranean diet and FMT independently reduced disease activity in a humanized UC mouse model, with FMT effects being donor-dependent and Mediterraneandiet strongly increasing alpha diversity. No significant interaction between diet and FMT was observed, highlighting the need for further mechanistic studies. Conflict of interest: Ms. Deleu, Sara: Grant: Sara Deleu has received the ECCO fellowship in 2024 and currently is an FWO junior postdoctoral fellow (1255426N). Other: Sara Deleu has been listed as a co-inventor on an international patent application entitled ‘Improved probiotic potency of the yeast Saccharomyces boulardii’ PCT/EP2023/051941. Troisi, Sara: No conflict of interest Masi, Letizia: No conflict of interest Emoli, Valeria: No conflict of interest to delcare Pane, Cesare: No conflict of interest do declare Migliore, Greta: No conflict of interest Foscarini, Elisa: No conflict of interest Profeta, Francesca: No conflict of interest Vidmar, Kaylynn: No conflict of interest Wargo, Hannah: No conflict of interest Williams, Joseph: No conflict of interest Artone, Serena: No conflict of interest De Santis, Stefania: No conflict of interest De Salvo, Carlo: No conflict of interest Scanu, Matteo: No conflict of interest Del Chierco, Federica: No conflict of interest Putignani, Lorenza: No conflict of interest Papa, Alfredo: No conflict of interest Petito, Valentina: No conflict of interest Lopetuso, Loris Riccardo: No conflict of interest Cominelli, Fabio: No conflict of interest Pizarro, Theresa: No conflict of interest Scaldaferri, Franco: Consultancy fee/board for Janseen, Takeda, Pfizer, MSD, Sandoz, Galapagos, Celltrion, Ferring, Abbvie, Lilly, Alfasigma, Abivax

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