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<p>The gut microbiota influences host metabolism, but the mechanisms of lipid uptake from food remain mysterious. Here we used stable isotope-labelled tracers in gnotobiotic mouse models, which revealed that host uptake of dietary lipids depends on microbial colonization. Systemic lipid metabolism modelling predicted that the gut microbiota restricts intestinal lipid absorption, and labelled lipid administration verified that the gut contents of microbiota-colonized mice contained up to 12-fold more lipids than those of germ-free animals. A combination of lipidomics and proteomics showed that gut microbes trigger Myd88 signalling, leading to a downregulation of hepatic Cyp7b1 activity and increased taurocholate production. Taurocholate stimulates phospholipase A1 activity in bile, causing the degradation of phosphatidylcholine that is essential for luminal micelle formation and lipid uptake. A diverse microbiome was associated with lower phosphatidylcholine content. This previously unrecognized host–gut microbiota interplay via enzymes in bile could provide future targets to modulate dietary lipid absorption.</p>

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Gut microbiota restricts intestinal lipid uptake via modulation of bile phosphatidylcholine metabolism in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月29日

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  • Sarah Brunner,
  • Johannes Plagge,
  • Maria Zimmermann-Kogadeeva,
  • Marcus Höring,
  • Gerhard Liebisch,
  • Marijana Basic,
  • Silvia Bolsega,
  • Klaus-Peter Janssen,
  • Emma Slack,
  • Sophia von Gamm,
  • Alina Viehof-Beckmann,
  • Thomas Clavel,
  • Michael Zimmermann,
  • Joerg Heeren,
  • Piero Giansanti,
  • Anna S. Weiss,
  • Sven Hermeling,
  • Aline Dupont,
  • Anna-Lena Ullrich,
  • Florian Jokisch,
  • Claudine Seeliger,
  • Andre Bleich,
  • Maria Hidrobo,
  • Bärbel Stecher,
  • Olivia I. Coleman,
  • Claudia Moresi,
  • Giorgia Greter,
  • Markus Arnoldini,
  • Josef Scheiber,
  • Silke Matysik,
  • Martin Klingenspor,
  • Bernhard Küster,
  • Dirk Haller,
  • Ralph Burkhardt,
  • Folkert Kuipers,
  • Josef Ecker

摘要

The gut microbiota influences host metabolism, but the mechanisms of lipid uptake from food remain mysterious. Here we used stable isotope-labelled tracers in gnotobiotic mouse models, which revealed that host uptake of dietary lipids depends on microbial colonization. Systemic lipid metabolism modelling predicted that the gut microbiota restricts intestinal lipid absorption, and labelled lipid administration verified that the gut contents of microbiota-colonized mice contained up to 12-fold more lipids than those of germ-free animals. A combination of lipidomics and proteomics showed that gut microbes trigger Myd88 signalling, leading to a downregulation of hepatic Cyp7b1 activity and increased taurocholate production. Taurocholate stimulates phospholipase A1 activity in bile, causing the degradation of phosphatidylcholine that is essential for luminal micelle formation and lipid uptake. A diverse microbiome was associated with lower phosphatidylcholine content. This previously unrecognized host–gut microbiota interplay via enzymes in bile could provide future targets to modulate dietary lipid absorption.