{
  "abstract": "BackgroundTuberculosis (TB) remains the leading infectious disease cause of mortality worldwide. A subset of individuals exposed to Mycobacterium tuberculosis (Mtb) remain TST/IGRA-negative despite sustained exposure, termed \"TB resisters\". The biological mechanisms underlying this resistance remain poorly understood. We applied untargeted high-resolution metabolomics to determine whether systemic metabolic profiles differ between TB resisters and matched Mtb-infected close contacts.\n\nMethodsWe compared untargeted high-resolution plasma metabolomics using liquid chromatography mass spectrometry between 269 TB resisters and 269 matched Mtb-infected close contacts, enrolled across Brazil, India, and South Africa. TB resisters were defined as highly exposed close contacts who slept in the same room or spent at least 5 hours indoors per day with an infectious pulmonary TB index patient, but remained TST/IGRA-negative. Mtb-infected close contacts were those who were TST/IGRA positive. Metabolome-wide association studies (MWAS) were conducted using paired t-tests.\n\nResultsThere were 1,787 features with nominal differences between TB resisters and matched Mtb-infected contacts (p < 0.05). Pathway enrichment identified fructose and mannose metabolism and bile acid biosynthesis in the overall cohort, while lipid-related pathways were enriched in Brazil. Among metabolites with confirmed chemical identities, glyceric acid concentrations were higher in TB resisters by 0.53 {micro}M, whereas hydroxyproline was lower by 0.90 {micro}M, butyrobetaine was lower by 0.06 {micro}M, and homogentisate was lower by 0.0036 {micro}M at false discovery rate of 0.2.\n\nConclusionsPlasma metabolomic profiles differed between TB resisters and matched Mtb-infected close contacts. These findings indicate that systemic metabolic differences are associated with resistance to Mtb infection.",
  "abstract_shown": true,
  "affiliations": [
    "Emory University"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "name": "C. Liu"
    },
    {
      "name": "J. M. Collins"
    },
    {
      "name": "M. F. Gyorfy"
    },
    {
      "name": "M. Araujo Pereira"
    },
    {
      "name": "V. Mave"
    },
    {
      "name": "S. Prakash"
    },
    {
      "name": "K. P. Devalraju"
    },
    {
      "name": "N. A. Martinson"
    },
    {
      "name": "F. Willis"
    },
    {
      "name": "M. C. Figueiredo"
    },
    {
      "name": "M. Cordeiro-Santos"
    },
    {
      "name": "A. Trancoso Lopo de Queiroz"
    },
    {
      "name": "V. S. K. Neela"
    },
    {
      "name": "R. Karyakarte"
    },
    {
      "name": "T. R. Sterling"
    },
    {
      "name": "J. J. Ellner"
    },
    {
      "name": "J. C. M. Brust"
    },
    {
      "name": "A. Gupta"
    },
    {
      "name": "B. B. Andrade"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. V. Sun"
    },
    {
      "name": "N. R. Gandhi"
    },
    {
      "name": "TB GWAS collaboration"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6206jp4hjzqjk.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.29.26364337",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.29.26364337v1.full",
  "id": "6206jp4hjzqjk",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.29.26364337v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "infectious diseases"
    ],
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7220460890",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.29.26364337v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6206jp4hjzqjk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "10.64898/2026.09.29.26364337",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.29.26364337v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:infectious diseases",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Metabolic Signatures of Resistance to Mycobacterium Tuberculosis Infection: Insights from a Multi-Country Plasma Metabolomics Study",
  "title_text": "Metabolic Signatures of Resistance to Mycobacterium Tuberculosis Infection: Insights from a Multi-Country Plasma Metabolomics Study",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/6206jp4hjzqjk",
  "venue": "medRxiv",
  "versions": []
}