{
  "abstract": "Background: Constipation can precede the motor diagnosis of Parkinson’s disease (PD), but its mechanisms are multifactorial. Gut bacteria can metabolize administered levodopa (LD), and enteric dopamine receptors participate in the regulation of motility. These observations motivate, but do not establish, a connection between microbial LD metabolism and constipation. Evidence: Bacterial tyrosine decarboxylase (TDC) converts LD to dopamine in biochemical and animal systems. Human studies associate fecal TDC abundance with some treatment and pharmacokinetic variables, but gene abundance does not measure enzyme activity. A longitudinal PD cohort found an inverse association between constipation severity and TDC abundance in one model, highlighting the need to consider medication effects and reverse causation. Microbiome alterations in risk-enriched populations do not demonstrate increased TDC activity before PD diagnosis. Hypothesis: In a subset of untreated individuals at increased risk of PD, sufficient luminal endogenous L-DOPA might permit microbial dopamine production that influences intestinal transit, provided that the resulting dopamine reaches relevant receptors at effective concentrations. Endogenous substrate availability, anatomical access, and the net balance of dopamine production and clearance are unresolved. After LD treatment begins, a larger exogenous substrate supply creates a distinct setting for drug–microbe interactions. Conclusions: The proposed continuum is conditional and requires biochemical and functional validation before human biomarker development. We propose substrate tracing, comparisons of TDC-positive and TDC-deficient bacteria, receptor-specific testing, and longitudinal gastrointestinal phenotyping. Current evidence does not justify TDC-directed dietary prevention of PD or clinical prediction from fecal TDC abundance alone.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Neurorehabilitation of Veruno Institute, Istituti Clinici Scientifici Maugeri IRCCS, 28013 Gattico-Veruno, Italy",
    "Research Laboratory in Biomechanics, Rehabilitation and Ergonomics, IRCCS, Istituto Auxologico Italiano, San Giuseppe Hospital, 28824 Piancavallo, Italy",
    "Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy",
    "Translational Immunology Institute, SingHealth/Duke-NUS Academic Medical Centre, Singapore 169856, Singapore",
    "National Neuroscience Institute, Singapore 308433, Singapore",
    "Department of Neurology, Singapore General Hospital, Singapore 169608, Singapore",
    "Duke-National University of Singapore Medical School, Singapore 169857, Singapore"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Giovanni Albani"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Paolo Capodaglio",
      "orcid": "0000-0003-3719-8789"
    },
    {
      "affs": [
        0
      ],
      "name": "Marica Giardini",
      "orcid": "0000-0002-8910-2649"
    },
    {
      "affs": [
        1
      ],
      "name": "Giuseppe Modaffari"
    },
    {
      "affs": [
        3
      ],
      "name": "Vasuki Ranjani Chellamuthu"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Yin-Xia Chao"
    },
    {
      "affs": [
        4
      ],
      "name": "Anusha Jayaraman"
    },
    {
      "affs": [
        3,
        6
      ],
      "name": "Salvatore Albani",
      "orcid": "0000-0002-5602-6256"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "Eng-King Tan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3ncb28szqsrsc.bib",
  "cited_by": 0,
  "doi": "10.3390/nu18213470",
  "fulltext_url": null,
  "id": "3ncb28szqsrsc",
  "issns": [
    "2072-6643"
  ],
  "landing_url": "https://www.mdpi.com/2072-6643/18/21/3470",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "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": "W7223225678",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/3ncb28szqsrsc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:56Z",
      "native_id": "10.3390/nu18213470",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6643/18/21/3470"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Gut Microbial Levodopa Metabolism and Constipation in Prodromal and Established Parkinson’s Disease",
  "title_text": "Gut Microbial Levodopa Metabolism and Constipation in Prodromal and Established Parkinson’s Disease",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:56Z",
  "url": "https://research.draconitic.com/paper/3ncb28szqsrsc",
  "venue": "Nutrients",
  "versions": []
}