{
  "abstract": "Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss in the substantia nigra (SN). Although the gut microbiota has been implicated in PD pathogenesis, how defined bacterial genes and their metabolites influence host neuronal gene regulation remains unclear. Here, we identify a gut microbial hns-methylglyoxal (MG) pathway linking Escherichia coli (E. coli) metabolism to host neuronal gene regulation. In the stool metagenomic cohort, hns, a bacterial gene encoding the histone-like nucleoid structuring protein and primarily derived from E. coli, was enriched particularly in body-first PD, a subtype associated with gut-originating pathology. In a separate plasma MG cohort, plasma levels of MG, a reactive metabolite whose bacterial production was hns-dependent in our model system, were higher in body-first than in brain-first PD and were nominally inversely associated with cardiac meta-iodobenzylguanidine (MIBG) uptake within the body-first group. Using Caenorhabditis elegans (C. elegans) PD models, we found that feeding with Δhns E. coli protected dopaminergic neurons, whereas exogenous MG abolished this neuroprotection. Transcriptomic and neuronal RNAi analyses identified rig-5 as a host mediator of hns deletion-induced neuroprotection. Cross-species analyses identified LSAMP as a candidate mammalian ortholog of rig-5. MG suppressed LSAMP expression in human neuronal cells, and LSAMP expression was reduced in the post-mortem SN of patients with PD. Conversely, Lsamp expression was increased in the SN of mice colonized with Δhns E. coli. Together, these findings delineate a microbial gene-metabolite-host gene pathway through which E. coli hns and MG modulate rig-5-dependent dopaminergic vulnerability in C. elegans, with corresponding changes of LSAMP expression in mammalian systems.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of Korea.",
    "Department of Biological Science, Kangwon National University, Chuncheon, Republic of Korea.",
    "Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea.",
    "BK21 R&E Initiative for Advanced Precision Medicine, Ajou University School of Medicine, Suwon, Republic of Korea.",
    "Department of Pharmacology, Ajou University School of Medicine, Suwon, Republic of Korea.",
    "Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.",
    "Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Min-Gi Shin",
      "orcid": "0000-0001-7278-9790"
    },
    {
      "affs": [
        0
      ],
      "name": "Soo Jung Park",
      "orcid": "0000-0002-8194-6134"
    },
    {
      "affs": [
        1
      ],
      "name": "Woorim Kang",
      "orcid": "0009-0005-1604-5785"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Yiseul Bae"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Suyeon Kim"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Dayeong Yoo"
    },
    {
      "affs": [
        0
      ],
      "name": "Seoyeon Yoon"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Sang Myun Park",
      "orcid": "0000-0002-1001-4743"
    },
    {
      "affs": [
        5
      ],
      "name": "Eun-Soo Kwon"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Jaerak Chang",
      "orcid": "0000-0003-1732-2076"
    },
    {
      "affs": [
        6
      ],
      "name": "Jung Han Yoon",
      "orcid": "0000-0001-6180-9848"
    },
    {
      "affs": [
        6
      ],
      "name": "Don Gueu Park",
      "orcid": "0000-0001-8658-3523"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Eun Jeong Lee",
      "orcid": "0000-0002-3507-5550"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2r34jt4z37x5w.bib",
  "cited_by": 0,
  "doi": "10.1080/19490976.2026.2739674",
  "fulltext_url": "https://europepmc.org/articles/PMC13679328",
  "id": "2r34jt4z37x5w",
  "issns": [
    "1949-0976",
    "1949-0984"
  ],
  "landing_url": "https://europepmc.org/article/MED/42878179",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7222350063",
  "pdf_url": "https://europepmc.org/articles/PMC13679328?pdf=render",
  "pmcid": "PMC13679328",
  "pmid": "42878179",
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2r34jt4z37x5w.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42878179",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42878179"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Escherichia coli hns and methylglyoxal link gut microbial metabolism to host neuronal gene regulation in Parkinson's disease.",
  "title_text": "Escherichia coli hns and methylglyoxal link gut microbial metabolism to host neuronal gene regulation in Parkinson's disease.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/2r34jt4z37x5w",
  "venue": "Gut microbes",
  "versions": []
}