Cross-species horse-to-dog fecal microbiota transplantation as a novel nature-inspired therapy for non-responsive chronic enteropathy in dogs

Introduction Canine chronic enteropathy (CE) is frequently associated with gut microbiota dysbiosis, and fecal microbiota transplantation (FMT) has emerged as a potential microbiota-modulating therapeutic approach. Methods This study evaluated the clinical outcomes and gut microbiota effects of a novel cross-species horse-to-dog FMT in 20 dogs with CE. Clinical response was assessed using the Canine Chronic Enteropathy Clinical Activity Index (CCECAI) at 30 days and approximately 1 year after treatment. Gut microbiota composition was characterized by 16S rRNA gene sequencing and compared with healthy reference dogs and the equine donor. Results At baseline, dogs with CE displayed reduced microbial diversity, marked compositional differences from healthy dogs, depletion of health-associated taxa, including members of Oscillospirales, Limosilactobacillus, Collinsella, and the Peptoclostridium complex, and enrichment of Escherichia-Shigella. Following FMT, 13/20 dogs (65%) showed a positive clinical response at 30 days and 16/20 (80%) were classified as long-term responders, with 13/20 (65%) achieving clinical remission at 1 year. At 30 days, no significant global changes in alpha or beta diversity were detected; however, ordination suggested a shift of post-FMT profiles toward the healthy reference configuration, accompanied by taxonomic changes consistent with partial microbiota restoration, including an increased relative abundance of Peptoclostridium-associated ASVs, including those putatively assigned to Peptoacetobacter hiranonis, and trends toward enrichment of Holdemanella and Turicibacter. ASV-sharing analysis revealed minimal persistence of horse-derived microorganisms in recipient dogs. A multilayer predictive analysis identified baseline Holdemanella and Parabacteroides as candidate markers of favorable clinical response, whereas Clostridium, Corynebacterium, Enterococcus, and Romboutsia were associated with poorer outcomes. Discussion These findings support further evaluation of cross-species horse-to-dog FMT as a therapeutic strategy for canine CE and suggest a predominantly biostimulatory mechanism acting on the resident gut microbiota.