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Systematic characterization of multi-omics landscape between gut microbial metabolites and GPCRome in Alzheimer's disease
Qiu Y, Hou Y, Gohel D, Zhou Y, Xu J, Bykova M, Yang Y, Leverenz JB et al.. Cell reports, 2024-04-21
Topic: Amyloid, tau and blood-test diagnosis
Shifts in the magnitude and nature of gut microbial metabolites have been implicated in Alzheimer's disease (AD), but the host receptors that sense and respond to these metabolites are largely unknown. Here, we develop a systems biology framework that integrates machine learning and multi-omics to identify molecular relationships of gut microbial metabolites with non-olfactory G-protein-coupled receptors (termed the "GPCRome"). We evaluate 1.09 million metabolite-protein pairs connecting 408 human GPCRs and 335 gut microbial metabolites. Using genetics-derived Mendelian randomization and integrative analyses of human brain transcriptomic and proteomic profiles, we identify orphan GPCRs (i.e., GPR84) as potential drug targets in AD and that triacanthine experimentally activates GPR84. We demonstrate that phenethylamine and agmatine significantly reduce tau hyperphosphorylation (p-tau181 and p-tau205) in AD patient induced pluripotent stem cell-derived neurons. This study demonstrates a systems biology framework to uncover the GPCR targets of human gut microbiota in AD and other complex diseases if broadly applied.
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APA 7th
Qiu, Y., Hou, Y., Gohel, D., Zhou, Y., Xu, J., Bykova, M., et al. (2024). Systematic characterization of multi-omics landscape between gut microbial metabolites and GPCRome in Alzheimer's disease. Cell reports. https://doi.org/10.1016/j.celrep.2024.114128
Vancouver
Qiu Y, Hou Y, Gohel D, Zhou Y, Xu J, Bykova M, et al. Systematic characterization of multi-omics landscape between gut microbial metabolites and GPCRome in Alzheimer's disease. Cell reports. 2024. doi:10.1016/j.celrep.2024.114128. PMID: 38652661.
BibTeX
@article{qiu2024-38652661,
author = {Qiu, Y. and Hou, Y. and Gohel, D. and Zhou, Y. and Xu, J. and Bykova, M. and Yang, Y. and Leverenz, J. B. and others},
title = {{Systematic characterization of multi-omics landscape between gut microbial metabolites and GPCRome in Alzheimer's disease}},
journal = {Cell reports},
year = {2024},
doi = {10.1016/j.celrep.2024.114128},
pmid = {38652661},
url = {https://doi.org/10.1016/j.celrep.2024.114128}
}
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Key findings
- We demonstrate that phenethylamine and agmatine significantly reduce tau hyperphosphorylation (p-tau181 and p-tau205) in AD patient induced pluripotent stem cell-derived neurons.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell reports) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38652661) |
| Free to read | 2 / 2 | Free to read |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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