Dietary modulation of intestinal microbes prolongs survival in a Hirschsprung disease mouse model.

Dietary changes that promote colon epithelial hypoxia and mitochondrial function tripled survival in a Hirschsprung disease mouse model, from a median of 4 to 12 days.

• Why it matters: Hirschsprung disease often leads to enterocolitis, a deadly complication with limited preventive options, highlighting the need for novel interventions to improve patient outcomes.
• What they did: Researchers analyzed how different diets affected survival, gut microbiome, and colon epithelial health in sl/sl mice, using metabolomics, microbiome sequencing, microscopy, gene expression, and microbial inhibition.
• The result: A protective diet increased colon hypoxia, mitochondrial activity, antimicrobial peptides, and beneficial metabolites like butyrate, while reducing Enterobacteriaceae, thereby significantly extending lifespan and suggesting dietary strategies to prevent disease complications.