{
  "abstract": "Detecting metabolic dysfunction-associated steatohepatitis (MASH) before fibrosis develops remains a major challenge. We used a longitudinal streptozotocin/high-fat diet (STAM/HFD) mouse model to identify microbial and metabolic features that emerge before histological MASH onset. Integrative 16S rRNA and untargeted LC-MS/MS analyses revealed microbial and metabolite shifts weeks before disease development. Lachnospiraceae and Oscillospiraceae were enriched in non-MASH mice and were negatively correlated with fatty acids elevated under MASH conditions. Bile acid and fatty acid metabolites enriched under MASH and non-MASH states varied with collection time, showing that diurnal variation strongly shapes biomarker profiles. Analysis of a human MAFLD cohort confirmed higher abundances of Lachnospiraceae bacteria in healthy participants. Our results identify early microbial and metabolic features that are associated with subsequent histologic MASH onset and reveal how temporal factors influence biomarker detection. These time-sensitive features, together with cross-species concordance in a human MAFLD cohort, lay the groundwork for developing and validating microbiome-based diagnostics and circadian-informed interventions that target the gut-liver axis to prevent metabolic liver disease. IMPORTANCE: Metabolic dysfunction-associated steatohepatitis (MASH) often develops silently, limiting opportunities for early intervention before fibrosis occurs. In this study, we identify gut microbial taxa and stool metabolites that are associated with future histologic MASH development in a longitudinal mouse model. We show that members of the Lachnospiraceae and Oscillospiraceae families are enriched in mice that remain disease-free and that members of the Lachnospiraceae family exhibit similar patterns in a human MAFLD cohort. Importantly, we demonstrate that time of sample collection has a strong effect on metabolomic profiles, with disease-associated lipid and bile acid signals detectable only at specific sampling times. These findings highlight circadian timing as a critical variable in microbiome-based biomarker discovery and support the development of time-aware diagnostic strategies for early MASH risk assessment.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Gastroenterology, University of California San Diego, La Jolla, California, USA",
    "Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA",
    "Department of Pediatrics, University of California San Diego, La Jolla, California, USA",
    "Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA",
    "Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA",
    "Department of Chemistry & Biochemistry, University of Denver, Denver, Colorado, USA",
    "Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, California, USA",
    "Department of Pathology, University of California San Diego, La Jolla, California, USA",
    "The Moores Cancer Center, University of California San Diego, La Jolla, California, USA",
    "NAFLD Research Center, Department of Medicine, University of California San Diego, La Jolla, California, USA",
    "Division of Epidemiology, Department of Family and Preventive Medicine, University of California San Diego, La Jolla, California, USA",
    "Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA",
    "Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, USA",
    "Halıcıoğlu Data Science Institute, University of California San Diego, La Jolla, California, USA",
    "Hong Kong University of Science and Technology Jockey Club Institute for Advanced Study, Hong Kong, China",
    "Synthetic Biology Institute, University of California San Diego, La Jolla, California, USA",
    "Division of Gastroenterology, Jennifer Moreno Department of Veterans Affairs Medical Center, La Jolla, California, USA",
    "Institute of Diabetes and Metabolic Health, University of California San Diego, La Jolla, California, USA",
    "Center for Circadian Biology and Medicine, University of California, San Diego, La Jolla, California, United States"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Stephany Flores Ramos",
      "orcid": "0000-0002-1918-9769"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kelly Fogelson"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Valentina B. Muti"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Allegra T. Aron"
    },
    {
      "affs": [
        2,
        6
      ],
      "name": "Rodolfo A. Salido"
    },
    {
      "affs": [
        0
      ],
      "name": "R. Alexander Richter",
      "orcid": "0009-0001-0434-3292"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Helena Mannochio-Russo",
      "orcid": "0000-0002-4961-2353"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Jingjing Hu",
      "orcid": "0000-0003-1957-2706"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Mojgan Hosseini"
    },
    {
      "affs": [
        0,
        9,
        10
      ],
      "name": "Rohit Loomba"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Pieter C. Dorrestein",
      "orcid": "0000-0002-3003-1030"
    },
    {
      "affs": [
        2,
        6,
        11,
        12,
        13,
        14
      ],
      "name": "Rob Knight",
      "orcid": "0000-0002-0975-9019"
    },
    {
      "affs": [
        0,
        6,
        8,
        11,
        15,
        16,
        17,
        18
      ],
      "name": "Amir Zarrinpar",
      "orcid": "0000-0001-6423-5982"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3hm004w3n4zvx.bib",
  "cited_by": 0,
  "doi": "10.1128/msystems.00720-26",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13712972/",
  "id": "3hm004w3n4zvx",
  "issns": [
    "2379-5077"
  ],
  "landing_url": "https://doi.org/10.1128/msystems.00720-26",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
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      "openalex",
      "1312|Gut microbiota and health"
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  "openalex": "W7212186532",
  "pdf_url": null,
  "pmcid": "PMC13712972",
  "pmid": "42720356",
  "published": "2026-09-10",
  "publisher": "American Society for Microbiology (ASM)",
  "ris": "https://research.draconitic.com/paper/3hm004w3n4zvx.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:23:27Z",
      "native_id": "PMC13712972",
      "source": "pmc",
      "url": "https://doi.org/10.1128/msystems.00720-26"
    }
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Gut microbiota and health",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Gut microbiome and metabolite profiles are associated with subsequent histologic MASH in a longitudinal mouse model",
  "title_text": "Gut microbiome and metabolite profiles are associated with subsequent histologic MASH in a longitudinal mouse model",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:27Z",
  "url": "https://research.draconitic.com/paper/3hm004w3n4zvx",
  "venue": "mSystems",
  "versions": []
}