JPGN Journal Club December 2024: Human Milk in Biliary Atresia and Type III Interferon–Induced Pyroptosis in Gut Epithelium

December’s almost here, can you believe it ?  Here’s JPGN Journal Club, led by Dr Jake Mann !  Don’t forget ESPGHAN’s other educational offerings :  https://www.espghan.org/knowledge-center – on XII.27 the MOOC Enteral Nutrition in Preterm Infants conference, on 2025.I.01 the Young ESPGHAN Mentorship Programme, on I.15 the GI Winter School, and on I.30 the Monothematic Conference on Steatotic Liver Disease in Children.    Jake’s choices for discussion today :  From J Pediatr Gastroenterol Nutr, by Tessler et al., “The association of human milk intake and outcomes in biliary atresia”, and from Cell, by Jena et al., “Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair”.  We learn from the JPGN article that whilst high-energy formula feeding may be recommended in patients with extrahepatic biliary atresia, a diet that includes some human milk helps infants grow better than does one of formula alone, albeit without significant impact on a variety of other parameters.  From the Cell article we learn that in both radiation enteritis and inflammatory bowel disease, gut damage and repair alter DNA configuration to yield Z-nucleic acids, which in combination with Z-DNA binding protein (Z-DBP) activate caspase-8.  This then cleaves gasdermin C, which triggers inflammatory cell death, or pyroptosis (distinct from apoptosis, non-inflammatory cell death).  Type III interferon induces the up-regulation of Z-DBP, promoting pyroptosis.  Agents that modulate type III interferon expression or activity thus may lessen injury in inflammatory bowel disease.     Literature Tessler MEM et al.  The association of human milk intake and outcomes in biliary atresia.  J Pediatr Gastroenterol Nutr 2024 Nov 11.  DOI :  10.1002/jpn3.12403.  PMID :  39526563   Jena KK et al.  Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair.  Cell 2024 Oct 30 S0092-8674(24)01158-9.  DOI :  10.1016/j.cell.2024.10.010.  PMID :  39500322