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Updated: Aug 12, 2025
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Assessing Hepatic Metabolic Changes During Progressive Colonization of Germ-free Mouse by 1H NMR Spectroscopy
Published on: December 15, 2011
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Host-microbe co-metabolism via MCAD generates circulating metabolites including hippuric acid
Kali M Pruss1, Haoqing Chen2, Yuanyuan Liu2
1Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Nature Communications
|January 31, 2023
Summary
The gut microbiome and host metabolism are linked through hippuric acid production. This study reveals a novel pathway involving gut bacteria and host medium-chain acyl-CoA dehydrogenase (MCAD) for processing microbial metabolites.
Area of Science:
- Microbiology
- Metabolomics
- Human Physiology
Background:
- The human gut microbiota generates numerous circulating metabolites impacting host health.
- The origins and metabolic fate of most microbial molecules remain poorly understood.
- Hippuric acid is a prevalent urinary organic acid with largely unknown origins.
Purpose of the Study:
- To elucidate the host-microbe co-metabolic pathway for hippuric acid generation.
- To identify additional microbial metabolites processed by the host.
- To investigate the role of medium-chain acyl-CoA dehydrogenase (MCAD) in metabolizing microbial products.
Main Methods:
- Stable isotope tracing to track metabolic pathways.
- Bacterial and host genetics, including the use of MCAD knockout mice.
- Gnotobiotic colonization and untargeted metabolomics.
Main Results:
- Demonstrated microbial reduction of phenylalanine to phenylpropionic acid.
- Showed host re-oxidation of phenylpropionic acid via MCAD.
- Identified other microbial metabolites processed by MCAD in host circulation.
Conclusions:
- Uncovered a novel host-microbe pathway for hippurate production from phenylalanine.
- Identified MCAD-mediated beta-oxidation as a key mechanism for metabolizing microbial metabolites.
- Highlighted the intricate interplay between gut microbiota and host metabolism.
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