Maternal MASLD rewires milk bile-acid hydrophobicity to restrict microbiome-dependent neonatal ketone supply_milk

ABSTRACT:

Maternal metabolic dysfunction-associated steatotic liver disease (MASLD) in mice creates a paradoxical neonatal ketone deficit during nursing, despite preserved hepatic ketogenesis, that precedes adult spatial memory impairment. Vulnerable litters show reduced β-hydroxybutyrate (β-HB) in the intestinal lumen, serum, and hippocampus. Increased milk bile-acid hydrophobicity is identified as an upstream determinant of a restrictive neonatal gut niche that suppresses microbiome-dependent depolymerization of poly-β-hydroxybutyrate (PHB) and limits portal β-HB delivery. Early hydrophilization of the neonatal bile-acid pool reopens this gut-to-brain ketone pathway, restores hippocampal β-HB, and prevents later memory impairment, whereas parenteral D-βHB bypass rescues brain ketone availability without correcting the upstream gut defect. A milk bile-acid hydrophobicity threshold prospectively identifies the rescuable high-risk state. These findings define a transferable postnatal metabolic checkpoint upstream of the liver.

INSTRUMENT(S): Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS15225 | MetaboLights | 2026-08-02

REPOSITORIES: MetaboLights