This study tested whether continuous oral succinate administration (150 mM in drinking water for 21 days) could model eosinophilic enteritis (EoN) in 4-week-old C57BL/6J mice, and used multiple knockout strains (Pou2f3, Il25, Il5, Il13, Rag2) to map the immunological pathway driving disease.
Succinate administration caused significant ileal eosinophil infiltration (p < 0.05) and failure to thrive (p < 0.001) via a tuft cell–IL-25–IL-5 axis; Pou2f3-knockout mice showed **complete** abolition of both inflammation and growth failure, while IL-13 deficiency selectively blocked tuft cell proliferation. Transcriptomic signatures overlapped with human eosinophilic colitis, especially IL-13 and serotonin receptor pathways.
- Mouse model only; direct translation to human non-EoE EGID pathogenesis is unconfirmed. - Transcriptomic overlap was with eosinophilic **colitis** datasets, not eosinophilic enteritis specifically, which may limit mechanistic conclusions. - Full-text was inaccessible; quantitative details (e.g., eosinophil counts, body weight deltas) could not be verified beyond the abstract.
While not yet clinically actionable, this model identifies the tuft cell–IL-25–ILC2 axis as a central driver of eosinophilic enteritis, suggesting IL-25 and IL-5 as potential therapeutic targets worth investigating in non-EoE EGIDs.
