What question did this study set out to answer?

The study aims to understand how gut microbiota from Crohn’s disease patients affects immune responses in a short bowel syndrome model.

January 23, 2026

P0176Exploring Microbiota-Immune Interactions in Short Bowel Syndrome and Crohn’s Disease in a model of human microbiota associated mice

Key Points

The study aims to understand how gut microbiota from Crohn’s disease patients affects immune responses in a short bowel syndrome model.
Human microbiota-associated mice were created using feces from Crohn’s disease patients.
A dextran sodium sulfate model was employed to induce colitis.
Fecal samples underwent 16S rRNA gene sequencing for microbiota profiling.
T cell populations were assessed through lymph node sample collection.
Disease activity was evaluated using endoscopy and a disease activity index.
Mice receiving low-risk no-resected donor feces showed higher disease activity index scores.
Endoscopic evaluations indicated more mucosal inflammation in the no-resected group.
Multivariate analysis displayed distinct microbiota profiles between resected and no-resected samples.
High-risk donor feces increased Th1/Th17 T cells, while low-risk enhanced Treg cell frequencies.

Abstract

Abstract Background Short bowel syndrome (SBS) is a malabsorptive condition mostly caused by massive surgical resection of the small intestine and is associated with significant morbidity and mortality, reduced quality of life, and high healthcare costs1. Crohn’s disease (CD) represents a potential cause leading to an increased risk of SBS with considerable clinical consequences2. Human microbiota-associated (HMA) mice represent a model to establish human fecal microbiota in preclinical models3-4. Here, for the first time, we tried to conduct a “humanized” model of SBS, using faeces from patients affected by this disease. The aim of the current study is to determine the functional role of the gut microbiota of CD patients with or without SBS. Methods A dextran sodium sulphate model of colitis on C57BL/6 mice was employed to assess immune and metabolic signatures following faecal transplantation from patients affected by SBS/IF, CD with high or low risk for SBS/IF. Fecal samples were processed for 16S rRNA gene sequencing (V3–V4 region) on the Illumina MiSeq platform, followed by standard bioinformatic analysis for taxonomic profiling, diversity metrics, and functional prediction. Lymph node samples were collected to examine differences in T cell populations, and disease activity index and bronchoscopy were used to evaluate the activity of the disease. Results Seven human fecal donors (CD High Risk, CD Low Risk resected/non-resected, and SBS) were used for FMT in antibiotic-treated DSS mice. During the recovery phase, mice receiving FMT from low risk no-resected donors displayed higher Disease Activity Index (DAI) scores and slower improvement compared with those colonized with microbiota from resected donors. Endoscopic evaluation confirmed more severe mucosal inflammation in the no-resected FMT group. Multivariate OPLS-DA analysis of gut microbiota composition revealed a clear separation between resected and no-resected profiles (R² = 0. 619; p = 0. 02). FMT from Crohn’s disease donors modulated intestinal T-cell subsets, increasing Th1/Th17 and memory cells in the high-risk group, while low-risk donors enhanced Treg frequencies. Conclusion Our data underscore the complex interactions between gut microbiota and host immunity and highlight the importance of careful donor selection in FMT applications, particularly for inflammatory conditions. Further research is warranted to characterize specific microbial and immunological factors that drive these effects and to identify microbiota profiles that could potentially confer therapeutic benefits. Founding: PNRR-MAD-2022-12376791Finanziato dall’Unione Europea – NextGenerationEU Titolo: Changing the future of intestinal failure in intestinal chronic inflammation: towards innovative predictive factors and therapeutic targets Conflict of interest: Mrs. Masi, Letizia: No conflict of interest Petito, Valentina: No conflict of interest Troisi, Sara: None Deleu, Sara: Grant: Sara Deleu has received the ECCO fellowship in 2024. 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. Scanu, Matteo: No conflict of interest Toto, Francesca: No conflict of interest Becherucci, Guia: No conflict of interest Migliore, Greta: No conflict of interest Pane, Cesare: No conflict of interest do declare Foscarini, Elisa: NA Profeta, Francesca: NA Del Chierico, Federica: No conflict of interest Putignani, Lorenza: No conflict of interest Lopetuso, Loris Riccardo: No conflict of interest Gasbarrini, Antonio: No conflict of interest Papa, Alfredo: No conflict of interest Scaldaferri, Franco: No conflict of interest

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Cite This Study

Masi et al. (Thu,) studied this question.

synapsesocial.com/papers/69730eabc8125b09b0d1e792 https://doi.org/https://doi.org/10.1093/ecco-jcc/jjaf231.357

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