Many circulating indole and phenol metabolites are host derived

Area of Science:

• Microbiology
• Metabolomics
• Human Physiology

Background:

• Indole and phenol metabolites are primarily attributed to bacterial digestion of amino acids like tryptophan and phenylalanine/tyrosine.
• These metabolites have significant physiological roles, including AhR signaling (indoles) and association with healthy body weight (phenols).
• The host's contribution to circulating pools of these metabolites remains undercharacterized.

Purpose of the Study:

• To investigate the host's role in producing circulating indole and phenol metabolites.
• To differentiate between host and microbial contributions to these metabolite pools.

Main Methods:

• Stable isotope tracing was employed in mammalian cell cultures and mouse models.
• Metabolite levels were analyzed in mice and human patients.
• The impact of microbiome perturbations on metabolite levels was assessed.

Main Results:

• Mammalian cells were shown to synthesize aryl-pyruvates, aryl-lactates, aryl-acetates, and aryl-carboxylic acids.
• Levels of these host-derived metabolites in mice and human patients were largely unaffected by microbiome changes.
• Bacterial metabolism was essential for producing aryl-propionates, free indole, phenol, and cresol.

Conclusions:

• Host metabolism is a major source of circulating aryl-pyruvates, -lactates, -acetates, and -carboxylic acids.
• Bacterial metabolism is crucial for the synthesis of specific indole and phenol derivatives like aryl-propionates and free indoles/phenols.
• Host contribution to circulating indole and phenol metabolite pools is significant and primary for certain metabolite classes.