Peer-reviewedCC BY-NC-NDNature Metabolism
Host metabolism can produce many indoles and phenols independently of the microbiome
13 affiliations
- 1Department of Molecular Biology, Princeton University, Princeton, NJ, USA
- 2Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA
- 3Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA
- 4Duchossois Family Institute, University of Chicago, Chicago, IL, USA
- 5Department of Chemistry, Princeton University, Princeton, NJ, USA
- 6German Cancer Research Center (DKFZ), Heidelberg, Division of Metabolic Crosstalk in Cancer and the German Cancer Consortium (DKTK), DKFZ Core Center Heidelberg, Heidelberg, Germany
- 7Department of Medicine, Section of Infectious Diseases & Global Health, University of Chicago Medicine, Chicago, IL, USA
- 8Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
- 9Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA
- 10Department of Chemistry, Princeton University, Princeton, NJ, USA. [email protected]
- 11Department of Molecular Biology, Princeton University, Princeton, NJ, USA. [email protected]
- 12Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA. [email protected]
- 13Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA. [email protected]
Abstract
Indole and phenol metabolites are typically thought to be products of bacterial digestion of tryptophan (indoles) and phenylalanine or tyrosine (phenols). Interest in controlling gut microbial production of these metabolites has continually grown because they have important physiological impacts, with indoles agonizing aryl hydrocarbon receptor signalling and phenols being associated with healthy body weight. Although there is a growing body of research on which bacteria produce these metabolites, the host contribution to their circulating pools has not been characterized. Here, through stable isotope tracing in cell culture, mice and rats, we show that mammalian cells can make aryl-pyruvates, aryl-lactates, aryl-acetates and aryl-carboxylic acids independently of the microbiome. We demonstrate that circulating levels of these metabolites in mice and human patients are robust to perturbations of the microbiome. By contrast, bacterial metabolism is required to synthesize aryl-propionates and free indole, phenol and p-cresol. Overall, these results suggest that host metabolism is a major contributor to circulating indole and phenol metabolite pools.
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BibTeX
@article{abusalim2026host,
title = {{Host metabolism can produce many indoles and phenols independently of the microbiome}},
author = {Jenna E. AbuSalim and Kellen L. Olszewski and Salma Youssef and Sarah Jayne Mitchell and Craig J. Hunter and Jessica C. Little and Ashley M. Sidebottom and Jacob A. Boyer and Steve D. Knutson and Laith Z. Samarah and Michael Robert MacArthur and Alessa Henneberg and Rolf-Peter Ryseck and Christiane A. Opitz and David W. C. MacMillan and Mohamed S. Donia and Eric G. Pamer and Sabrina Imam and Christopher J. Lehmann and Olatoyosi M. Odenike and Joshua D. Rabinowitz},
journal = {Nature Metabolism},
year = {2026},
month = jun,
doi = {10.1038/s42255-026-01550-8},
url = {https://doi.org/10.1038/s42255-026-01550-8},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Host metabolism can produce many indoles and phenols independently of the microbiome
AU - Jenna E. AbuSalim
AU - Kellen L. Olszewski
AU - Salma Youssef
AU - Sarah Jayne Mitchell
AU - Craig J. Hunter
AU - Jessica C. Little
AU - Ashley M. Sidebottom
AU - Jacob A. Boyer
AU - Steve D. Knutson
AU - Laith Z. Samarah
AU - Michael Robert MacArthur
AU - Alessa Henneberg
AU - Rolf-Peter Ryseck
AU - Christiane A. Opitz
AU - David W. C. MacMillan
AU - Mohamed S. Donia
AU - Eric G. Pamer
AU - Sabrina Imam
AU - Christopher J. Lehmann
AU - Olatoyosi M. Odenike
AU - Joshua D. Rabinowitz
PY - 2026
DA - 2026/06/23
JO - Nature Metabolism
DO - 10.1038/s42255-026-01550-8
UR - https://doi.org/10.1038/s42255-026-01550-8
AB - Indole and phenol metabolites are typically thought to be products of bacterial digestion of tryptophan (indoles) and phenylalanine or tyrosine (phenols). Interest in controlling gut microbial production of these metabolites has continually grown because they have important physiological impacts, with indoles agonizing aryl hydrocarbon receptor signalling and phenols being associated with healthy body weight. Although there is a growing body of research on which bacteria produce these metabolites, the host contribution to their circulating pools has not been characterized. Here, through stable isotope tracing in cell culture, mice and rats, we show that mammalian cells can make aryl-pyruvates, aryl-lactates, aryl-acetates and aryl-carboxylic acids independently of the microbiome. We demonstrate that circulating levels of these metabolites in mice and human patients are robust to perturbations of the microbiome. By contrast, bacterial metabolism is required to synthesize aryl-propionates and free indole, phenol and p-cresol. Overall, these results suggest that host metabolism is a major contributor to circulating indole and phenol metabolite pools.
SN - 2522-5812
ER -