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Select microbial metabolites promote tau aggregation in a murine tauopathy model.

Overview

Authors: Sabeen A Kazmi1, Franciscus Chandra1, Michael Wasney2, Jenny Cheng1, Gregory R Lum1, Malvika Iyer1, Daria Di Blasi1, Adriana N Espinoza3, Arlene Lopez-Romero3, Xia Yang1, Nandita Garud2, Elaine Y Hsiao1,3
ORCID iDs: Sabeen A Kazmi, Franciscus Chandra, Gregory R Lum, Arlene Lopez-Romero, Xia Yang, Nandita Garud, Elaine Y Hsiao
  1. Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA USA
  2. Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, CA USA
  3. UCLA Goodman-Luskin Microbiome Center, Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, Los Angeles, CA USA
Institutions: University of California, Los Angeles (United States)
Journal: Nature communications, volume 17, issue 1, article 8161
Dates: received 31 March 2026; accepted 11 June 2026; published online 30 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-74775-6 · PMID 42380200 · PMCID PMC13458332 · OpenAlex W7166647506
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics, Smoothing, state filtering, decompositions, Machine learning, fMRI & imaging
Keywords: Microbiome, Alzheimer's disease
MeSH: Gastrointestinal Microbiome*, Protein Aggregation, Pathological*, tau Proteins*, Tauopathies*, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Female, Humans, Male, Mice, Mice, Transgenic (* major topic)
Topic: Gut microbiota and health (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Silicon Valley Community Foundation (SVCF) (2018-191860)
Citations: not cited yet (Europe PMC); 80 references in the paper

Abstract

The gut microbiome is emerging as a modifier of risk for neurodegenerative diseases, but underlying mechanisms remain poorly understood. Here, we show that the hTau.P301S mouse model for progressive tauopathy develops alterations in the composition and function of the gut microbiome that are not recapitulated in amyloid-based 5xFAD or 3xTg models for Alzheimer’s disease. Disrupting the gut microbiome via chronic antibiotic treatment exacerbates cognitive deficits and tau pathology in hTau.P301S mice, demonstrating a causal influence of the microbiome on tau-driven disease progression. This corresponds with widespread alterations in microbiome-dependent metabolites in the sera and brains of hTau.P301S mice, including subsets that correlate with the severity of tau pathology. By screening against tau biosensor cells, we identify select microbial metabolites—trimethylamine-N-oxide, 3-indoxyl sulfate, phenol sulfate, thymidine, and 2’deoxyuridine—that promote tau seeding and aggregation. Systemic administration of these metabolites worsens cognitive impairment and tau pathology in hTau.P301S mice. These findings establish a mechanistic link between the gut microbiome, serum and brain metabolites, as well as tau aggregation, suggesting that select microbial metabolites could potentially serve as therapeutic targets for tau-driven diseases.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

Datasets cited

Data availability

All data are available in the article and its supplementary information files. The following data has also been deposited to the data repositories as indicated. Data from 16S rRNA gene sequencing, metagenomic profiling, and associated metadata are available online through the NCBI Sequence Read Archive (SRA) repository at https://www.ncbi.nlm.nih.gov/sra/PRJNA1338993. Metabolomic data are available online through Mendeley Data 10.17632/dvyvkrb59z.2. Source data are provided with this paper.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 2 keywords, 13 MeSH terms, 1 funder, 77 references.

Cite

This paper

Kazmi, S. A., Chandra, F., Wasney, M., Cheng, J., Lum, G. R., Iyer, M., Di Blasi, D., Espinoza, A. N., Lopez-Romero, A., Yang, X., Garud, N., & Hsiao, E. Y. (2026). Select microbial metabolites promote tau aggregation in a murine tauopathy model. Nature communications, 17(1), 8161. https://doi.org/10.1038/s41467-026-74775-6

BibTeX

@article{kazmi2026select,
author = {Kazmi, Sabeen A and Chandra, Franciscus and Wasney, Michael and Cheng, Jenny and Lum, Gregory R and Iyer, Malvika and Di Blasi, Daria and Espinoza, Adriana N and Lopez-Romero, Arlene and Yang, Xia and Garud, Nandita and Hsiao, Elaine Y},
title = {{Select microbial metabolites promote tau aggregation in a murine tauopathy model}},
journal = {Nature communications},
year = {2026},
month = jun,
volume = {17},
number = {1},
pages = {8161},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-74775-6},
url = {https://doi.org/10.1038/s41467-026-74775-6},
pmid = {42380200},
pmcid = {PMC13458332}
}

RIS

TY - JOUR
AU - Kazmi, Sabeen A
AU - Chandra, Franciscus
AU - Wasney, Michael
AU - Cheng, Jenny
AU - Lum, Gregory R
AU - Iyer, Malvika
AU - Di Blasi, Daria
AU - Espinoza, Adriana N
AU - Lopez-Romero, Arlene
AU - Yang, Xia
AU - Garud, Nandita
AU - Hsiao, Elaine Y
TI - Select microbial metabolites promote tau aggregation in a murine tauopathy model
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/06/30
VL - 17
IS - 1
SP - 8161
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-74775-6
UR - https://doi.org/10.1038/s41467-026-74775-6
LA - en
ER -

CSL-JSON

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