{
  "abstract": "Background: Lysosomal pathways influence host–microbe interactions, but the microbiome consequences of lysosomal dysfunction remain incompletely defined. LAMP2 is required for autophagosome–lysosome fusion, and pathogenic variants in LAMP2 cause Danon disease. Whether Lamp2 loss alters the gut microbiome in vivo has not been systematically evaluated using methods that profile both taxonomic composition and microbial functional potential, such as shotgun metagenomics. Methods: We performed shotgun metagenomic sequencing on 50 fecal samples from male Lamp2 knockout (Lamp2KO) mice and wild-type (WT) littermates sampled at 3, 6, 9, and 12 months under single-genotype cages or mixed-genotype cohousing. Two low-depth libraries (<3 × 105 classified genus-level reads) were excluded from primary inference (primary set: n = 48). We analyzed genus-level alpha diversity, beta diversity, and differential abundance using compositional, cage-aware mixed-effects models and cage-blocked permutation testing. We analyzed functional pathway profiles using copies-per-million abundances with centered-log-ratio transformation and mixed-effects modeling. We controlled multiple testing using the Benjamini–Hochberg false discovery rate. Results: In the primary set (48 samples from 27 cages), Lamp2KO and WT mice showed similar genus-level alpha diversity and overall community composition (PERMANOVA using Aitchison and Bray–Curtis distances). Primary mixed-effects models detected no genera with differential abundance after false discovery rate correction. Taxonomic profiles were broadly similar between genotypes and were dominated by Bacteroidota and Bacillota. Exploratory within-cage (paired) analyses identified consistent directional differences in a small set of genera, but these signals were not supported by the primary mixed-effects models. Functional pathway profiles were similar between genotypes; one pathway (dTDP-β-L-rhamnose biosynthesis) showed an exploratory association (FDR q < 0.10) within the 50 most abundant pathways. Conclusions: In this controlled mouse cohort, we did not detect robust, cage-independent shifts in fecal microbiome composition or inferred functional pathway profiles associated with Lamp2 deficiency under standard SPF husbandry and chow; given the sample size, smaller or compartment-specific effects cannot be excluded.",
  "abstract_shown": true,
  "affiliations": [
    "Angiogenesis Laboratory, Ines and Frederick Yeatts Retina Research Laboratory, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America",
    "NYU Langone Health, NYU Grossman School of Medicine, New York, New York, United States of America",
    "Department of Ophthalmology, National and Kapodistrian University of Athens, Athens, Greece"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Maria Emfietzoglou"
    },
    {
      "affs": [
        1
      ],
      "name": "Maria Anna Bantounou"
    },
    {
      "affs": [
        2
      ],
      "name": "Shewa Osmani"
    },
    {
      "name": "Toshio Narimatsu"
    },
    {
      "name": "Konstantinos G. Baroutis"
    },
    {
      "name": "Alexandra Varsamidaki"
    },
    {
      "name": "Dimitra Skondra"
    },
    {
      "name": "Dimitris Papaconstantinou"
    },
    {
      "name": "Panagiotis Theodossiadis"
    },
    {
      "name": "Irini Chatziralli"
    },
    {
      "name": "Joan W. Miller"
    },
    {
      "name": "Demetrios G. Vavvas"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8z6e9x6mas3vp.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0357009",
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  "id": "8z6e9x6mas3vp",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0357009",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Gut microbiota and health"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Lysosomes"
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      "/Biology and life sciences/Microbiology/Microbial genomics/Microbiome"
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      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Cloning/DNA cloning/Shotgun sequencing"
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  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0357009&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/8z6e9x6mas3vp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
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      "url": "https://doi.org/10.1371/journal.pone.0357009"
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  "subjects": [
    {
      "field": "biology",
      "origin": "plos:ecology",
      "subfield": "ecology"
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    {
      "field": "biology",
      "origin": "plos:microbiology",
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  "title": "Shotgun metagenomic profiling of the fecal microbiome in Lamp2 knockout mice reveals limited genotype-associated differences under standard housing",
  "title_text": "Shotgun metagenomic profiling of the fecal microbiome in Lamp2 knockout mice reveals limited genotype-associated differences under standard housing",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/8z6e9x6mas3vp",
  "venue": "PLOS One",
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