Fecal microbiota transplantation in murine models of colitis and short bowel syndrome: lessons learned, limitations, and translational perspectives.

Abstract

Fecal microbiota transplantation (FMT) has become a powerful experimental tool for dissecting microbiota-driven mechanisms in murine models of gastrointestinal and systemic disease. This review provides a comprehensive methodological and translational overview of FMT in mice, focusing on lessons learned from inflammatory bowel disease (IBD) research and emerging perspectives in short bowel syndrome (SBS). We first outline the fundamental role of the gut microbiota in immune regulation, metabolic homeostasis, and maintenance of epithelial barrier integrity, establishing the rationale for modulating microbial communities through FMT. A detailed methodological analysis follows, highlighting how donor selection, recipient conditioning, sample handling, administration route, and environmental variables critically influence microbial engraftment and experimental reproducibility. The review then synthesizes current evidence from key murine IBD models, demonstrating that FMT can restore epithelial integrity, rebalance adaptive immunity, modulate cytokine networks, and enrich beneficial short-chain fatty-acid-producing taxa. Concepts such as functional engraftment, viability of transferred communities, and host-microbe metabolic interactions are discussed as central determinants of FMT efficacy. Finally, we address the emerging but challenging application of FMT in SBS. Profound alterations in intestinal anatomy, transit, oxygen tension, and substrate availability limit the integration of donor microbiota in SBS models, necessitating adapted strategies such as anaerobic handling, pre-conditioned consortia, synbiotics, and optimized delivery systems. Piglet models and computational approaches for donor-recipient matching are highlighted as promising translational tools. Overall, this review underscores the need for methodological standardization and physiologically tailored approaches to advance the reliability, mechanistic insight, and translational potential of FMT in both IBD and SBS.