Evidence map›Paper›PMID 41955304›Full record

ArticleHuman molecular genetics2026

A microbiome quantitative trait locus in SLC39A8 modulates disease severity in synucleinopathy-induced models of Parkinson's disease.

Julianne C Yang, Jamilla Situ, Ryan Troutman, Ruowei Zhu, Margaret Black, Heidi Buri, Arjun Gutta, Fengrui Tian, Allyson Kang, Ezinne Aja and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Julianne C YangThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.ORCID 0000-0001-5898-7221
Jamilla SituThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Ryan TroutmanThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Ruowei ZhuDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 300 Medical Plaza, Los Angeles, CA 90095, United States.
Margaret BlackThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Heidi BuriThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Arjun GuttaThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Fengrui TianThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Allyson KangThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Ezinne AjaThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.ORCID 0000-0003-2146-3541
Amber ZengThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Rochelle W LaiDivision of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Jia TanDepartment of Pediatric Endocrinology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Fengting LiangThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Caitlyn BrahimThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Grace MurphyThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Aaron AhdootThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.
Chao PengDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 300 Medical Plaza, Los Angeles, CA 90095, United States.
Jonathan P JacobsThe Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 100 Medical Plaza, Los Angeles, CA 90095, United States.ORCID 0000-0003-4698-0254

Funding

CSRD VA IK2 CX001717
6 · The paper itself

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor deficits, dopaminergic neuron loss, and α-synuclein (α-syn) aggregation. While rare mutations underlie familial PD, around 85% of cases are idiopathic. Emerging evidence implicates common genetic variants and the gut microbiome in PD risk, but their interaction has not been studied. We previously demonstrated that the PD-protective SLC39A8 variant rs13107325 (human A391T, corresponding to A393T in mouse) is associated with microbial compositional shifts in humans and reshapes the microbiome in SLC39A8 A393T knock-in mice. Here, we test whether this SNP modifies PD phenotypes in two α-synucleinopathy mouse models. In the human α-synuclein overexpression model, A393T carrier mice show reduced motor deficits, consistent with a protective role. However, in the α-synuclein preformed fibril (PFF) injection model, A393T carriers exhibit worsened motor deficits, increased dopaminergic terminal loss, and enhanced α-synuclein pathology spread. SNP- and model-specific microbiome changes correlated with motor outcomes. These included enrichment of Lactobacillus and Lactobacillaceae HT002 genera in A393T carriers with α-synuclein overexpression, and enrichment of Erysipelatoclostridium in PFF-injected A393T carriers. These findings suggest that SLC39A8 A393T-induced microbiome alterations are associated with differential disease outcomes depending on context. Our results are consistent with a model in which susceptibility gene SNPs may influence PD progression via the gut microbiome, though direct causal effects remain to be tested.

Indexed as

Cation Transport ProteinsGastrointestinal MicrobiomeParkinson DiseaseQuantitative Trait LociSynucleinopathiesalpha-SynucleinAnimalsDisease Models, AnimalDopaminergic NeuronsHumansMaleMiceMice, TransgenicPolymorphism, Single Nucleotidealpha-SynucleinCation Transport ProteinsSLC39A8 protein, humanGene-microbiome interactiongut microbiomembQTLmicrobiome quantitative trait locusParkinson’s diseaseSLC39A8

Identifiers

PMID41955304
PMCPMC13069889

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.