Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 41 min ago
Peer-reviewedCC BYGut microbes

Escherichia coli hns and methylglyoxal link gut microbial metabolism to host neuronal gene regulation in Parkinson's disease.

  • Min-Gi Shin1
  • Soo Jung Park1
  • Woorim Kang2
  • Yiseul Bae1,3,4
  • Suyeon Kim1,3,4
  • Dayeong Yoo1,3,4
  • Seoyeon Yoon1
  • Sang Myun Park3,4,5
  • Eun-Soo Kwon6
  • Jaerak Chang1,3,4
  • Jung Han Yoon7
  • Don Gueu Park7
1 more authors
  • Eun Jeong Lee1,3,4
7 affiliations
  1. 1Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of Korea.
  2. 2Department of Biological Science, Kangwon National University, Chuncheon, Republic of Korea.
  3. 3Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea.
  4. 4BK21 R&E Initiative for Advanced Precision Medicine, Ajou University School of Medicine, Suwon, Republic of Korea.
  5. 5Department of Pharmacology, Ajou University School of Medicine, Suwon, Republic of Korea.
  6. 6Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
  7. 7Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea.
Read full textPDFDOICite

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.

Related

  1. Dopamine Metabolism as a Chemically Constrained Network: Structural Regulation, Redox Liability and Dopaminergic Vulnerability in Parkinson’s Disease
    Emmanuel Ortega-Robles, Magdalena Guerra-Crespo, Oscar Arias-Carrión
    Medical sciences (Basel, Switzerland)Peer-reviewedCC BYFull textGeneral medicineEurope PMC
  2. Gut Microbial Levodopa Metabolism and Constipation in Prodromal and Established Parkinson’s Disease
    Giovanni Albani, Paolo Capodaglio, Marica Giardini +6
    NutrientsPeer-reviewedCC BY 4.0NeurologyCrossref
  3. Metabolic regulation of the carbonyl stress pathway and methylglyoxal in Lyme disease and relapsing fever spirochetes
    Dan Drecktrah, Laura S. Hall, Britney Cheff +6
    PLOS PathogensPeer-reviewedCC BY 4.0Full textInfectious diseasePhysiologyPLOS
  4. The Gut–Kidney Axis in Chronic Kidney Disease: Microbial Dysbiosis, Host–Microbial Metabolism, and Emerging Therapeutic Strategies
    Louise Vijverman, Too Maddalena, Charlotte Delrue +1
    BiomedicinesPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  5. TRPML1 inhibitor ML-SI1 suppresses prostate cancer through dual regulation of androgen receptor and polyamine metabolism
    Jiongzheng Li, Jipeng Ding, Hongfei Wei +6
    Frontiers in medicinePeer-reviewedCC BYFull textGeneral medicineEurope PMC

Cite

BibTeXRIS
BibTeX
@article{shin2026escherichia,
  title = {{Escherichia coli hns and methylglyoxal link gut microbial metabolism to host neuronal gene regulation in Parkinson's disease.}},
  author = {Min-Gi Shin and Soo Jung Park and Woorim Kang and Yiseul Bae and Suyeon Kim and Dayeong Yoo and Seoyeon Yoon and Sang Myun Park and Eun-Soo Kwon and Jaerak Chang and Jung Han Yoon and Don Gueu Park and Eun Jeong Lee},
  journal = {Gut microbes},
  year = {2026},
  month = oct,
  doi = {10.1080/19490976.2026.2739674},
  url = {https://europepmc.org/article/MED/42878179},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Escherichia coli hns and methylglyoxal link gut microbial metabolism to host neuronal gene regulation in Parkinson's disease.
AU  - Min-Gi Shin
AU  - Soo Jung Park
AU  - Woorim Kang
AU  - Yiseul Bae
AU  - Suyeon Kim
AU  - Dayeong Yoo
AU  - Seoyeon Yoon
AU  - Sang Myun Park
AU  - Eun-Soo Kwon
AU  - Jaerak Chang
AU  - Jung Han Yoon
AU  - Don Gueu Park
AU  - Eun Jeong Lee
PY  - 2026
DA  - 2026/10/15
JO  - Gut microbes
DO  - 10.1080/19490976.2026.2739674
UR  - https://europepmc.org/article/MED/42878179
AB  - 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.
SN  - 1949-0976
SN  - 1949-0984
ER  -