Gut dysbiosis and metabolic disruption distinguish continence outcomes after anorectal malformation repair

Faecal incontinence (FI) is a frequent and debilitating sequela of surgical repair of anorectal malformations (ARMs). The rectoanal inhibitory reflex (RAIR), an enteric nervous system (ENS)-mediated circuit essential for continence, is often absent or impaired in these children post-surgically. However, the biological cascade linking surgery to this reflex failure remains unknown. To identify the mechanistic pathways underlying post-surgical FI, we performed a multi-omics case-control study of 31 post-ARM children (12 incontinent, 20 continent), integrating stool 16S rRNA sequencing with untargeted serum metabolomics by liquid chromatography-mass spectrometry (LC-MS). Incontinent children exhibited greater microbial richness yet distinct communities, marked by depletion of butyrate-producing Faecalibacterium and expansion of mucin-degrading Ruminococcus along with Proteobacteria. These ecological shifts coincided with signatures of impaired fatty acid oxidation, and elevated levels of neurotoxic and inflammatory compounds such as trimethylamine and kynurenines. These findings suggest that surgical trauma destabilizes microbial and metabolic homeostasis, compromising ENS circuits. These results raise the possibility that microbial and metabolic restoration could restore faecal continence after surgical repair.