• Hepatocyte PLD1 knockout significantly alters gut microbiota composition in MASLD mice, reducing Pseudomonadota and Candidatus Bathyarchaeota at the phylum level.
• PLD1 deficiency modulates intestinal bile acid profiles, with notable changes in hyodeoxycholic acid and glycolithocholic acid levels.
• Correlation analysis reveals associations between specific gut bacteria (e.g., Faecalibaculum, Bacteroides uniformis) and bile acids, suggesting a microbiota-bile acid axis.
• Mass spectrometry imaging shows decreased hepatic TCA and TDCA levels after PLD1 knockout, indicating potential therapeutic targets for MASLD.