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Decreased circulating IPA levels identify subjects with metabolic comorbidities: A multi-omics study
Marta Ballanti1, Lorenzo Antonetti2, Maria Mavilio2
1Center for Atherosclerosis and Internal Medicine Unit, Policlinico Tor Vergata University Hospital, Via Oxford 81, Rome 00133, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy.
Indole-3-propionic acid (IPA), a gut microbe product, is linked to metabolic health. Low IPA levels correlate with insulin resistance, while IPA treatment in mice improved glucose tolerance, suggesting potential therapeutic benefits for dysbiosis.
Area of Science:
- Microbiome research
- Metabolic homeostasis
- Gut-liver axis
Background:
- Gut microbiome metabolites influence metabolic health.
- Indole-3-propionic acid (IPA), a tryptophan metabolite, has shown variable effects on metabolic and cardiovascular diseases.
- IPA is primarily produced by Clostridium sporogenes.
Purpose of the Study:
- To characterize clinical and multi-omics profiles of individuals with low versus high IPA blood levels.
- To investigate the therapeutic potential of IPA in a mouse model of metabolic dysfunction.
Main Methods:
- Clinical data collection and multi-omics analysis (metabolomics, transcriptomics, metagenomics) in human subjects.
- IPA administration in a mouse model to assess effects on glucose tolerance, insulin signaling, and gene expression.
- Correlation analysis between IPA levels and specific microbial taxa and metabolic pathways.
Main Results:
- Low IPA levels in humans were associated with insulin resistance, overweight, inflammation, and metabolic syndrome features.
- IPA levels negatively correlated with branched-chain amino acid (BCAA) metabolism (leucine, isoleucine, valine).
- IPA treatment in mice improved glucose tolerance, Akt phosphorylation, and modulated colon gene expression, mirroring human findings.
Conclusions:
- Human gut microbiome composition differs significantly between high and low IPA level groups.
- IPA treatment may represent a therapeutic strategy for improving insulin resistance in individuals with gut dysbiosis.
- IPA's role in metabolic regulation warrants further investigation.
