{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Biology, Princeton University, Princeton, NJ, USA",
    "Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA",
    "Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA",
    "Duchossois Family Institute, University of Chicago, Chicago, IL, USA",
    "Department of Chemistry, Princeton University, Princeton, NJ, USA",
    "German Cancer Research Center (DKFZ), Heidelberg, Division of Metabolic Crosstalk in Cancer and the German Cancer Consortium (DKTK), DKFZ Core Center Heidelberg, Heidelberg, Germany",
    "Department of Medicine, Section of Infectious Diseases & Global Health, University of Chicago Medicine, Chicago, IL, USA",
    "Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA",
    "Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA",
    "Department of Chemistry, Princeton University, Princeton, NJ, USA. joshr@princeton.edu",
    "Department of Molecular Biology, Princeton University, Princeton, NJ, USA. joshr@princeton.edu",
    "Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA. joshr@princeton.edu",
    "Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA. joshr@princeton.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jenna E. AbuSalim",
      "orcid": "0000-0002-5870-6984"
    },
    {
      "affs": [
        2
      ],
      "name": "Kellen L. Olszewski",
      "orcid": "0000-0001-9691-0831"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Salma Youssef",
      "orcid": "0009-0005-3499-7755"
    },
    {
      "affs": [
        2
      ],
      "name": "Sarah Jayne Mitchell",
      "orcid": "0000-0002-4027-3754"
    },
    {
      "affs": [
        1
      ],
      "name": "Craig J. Hunter"
    },
    {
      "affs": [
        3
      ],
      "name": "Jessica C. Little"
    },
    {
      "affs": [
        3
      ],
      "name": "Ashley M. Sidebottom",
      "orcid": "0000-0002-8670-9090"
    },
    {
      "affs": [
        2
      ],
      "name": "Jacob A. Boyer"
    },
    {
      "affs": [
        4
      ],
      "name": "Steve D. Knutson",
      "orcid": "0000-0001-6822-464X"
    },
    {
      "affs": [
        4,
        1,
        2
      ],
      "name": "Laith Z. Samarah",
      "orcid": "0000-0003-1358-2727"
    },
    {
      "affs": [
        4,
        1,
        2
      ],
      "name": "Michael Robert MacArthur",
      "orcid": "0000-0003-3593-6995"
    },
    {
      "affs": [
        5
      ],
      "name": "Alessa Henneberg",
      "orcid": "0000-0001-9704-6045"
    },
    {
      "affs": [
        1
      ],
      "name": "Rolf-Peter Ryseck",
      "orcid": "0000-0001-5129-7332"
    },
    {
      "affs": [
        5
      ],
      "name": "Christiane A. Opitz",
      "orcid": "0000-0001-5575-9821"
    },
    {
      "affs": [
        4
      ],
      "name": "David W. C. MacMillan"
    },
    {
      "affs": [
        0
      ],
      "name": "Mohamed S. Donia",
      "orcid": "0000-0002-9604-2912"
    },
    {
      "affs": [
        6
      ],
      "name": "Eric G. Pamer",
      "orcid": "0000-0002-6755-9904"
    },
    {
      "affs": [
        7
      ],
      "name": "Sabrina Imam"
    },
    {
      "affs": [
        6
      ],
      "name": "Christopher J. Lehmann",
      "orcid": "0000-0002-1111-2169"
    },
    {
      "affs": [
        8
      ],
      "name": "Olatoyosi M. Odenike",
      "orcid": "0000-0002-4027-4124"
    },
    {
      "affs": [
        9,
        10,
        11,
        12
      ],
      "name": "Joshua D. Rabinowitz",
      "orcid": "0000-0002-1247-4727"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cxkt1v66fwwmv.bib",
  "cited_by": 13,
  "doi": "10.1038/s42255-026-01550-8",
  "fulltext_url": null,
  "id": "cxkt1v66fwwmv",
  "issns": [
    "2522-5812"
  ],
  "landing_url": "https://doi.org/10.1038/s42255-026-01550-8",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Gut microbiota and health"
    ]
  ],
  "openalex": "W7165614935",
  "pdf_url": null,
  "pmcid": "PMC13400307",
  "pmid": "42337138",
  "published": "2026-06-23",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/cxkt1v66fwwmv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:48Z",
      "native_id": "W7165614935",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s42255-026-01550-8"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Gut microbiota and health",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Host metabolism can produce many indoles and phenols independently of the microbiome",
  "title_text": "Host metabolism can produce many indoles and phenols independently of the microbiome",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:05Z",
  "url": "https://research.draconitic.com/paper/cxkt1v66fwwmv",
  "venue": "Nature Metabolism",
  "versions": []
}