RNA-sequencing of butyrate-treated human lymphoblastoid cell lines shows dysregulated genes of multiple disease-related pathways
Volkov H, Cohen T, Shlayem R, Shapira E, Voinsky I, Klin H, Grad M, Shomron N et al.. bioRxiv, 2026-10-24
Topic: Gut, metabolism and diet
Butyrate, a 4-carbon fatty acid produced from insoluble starch by the gut microbiome, plays key roles in mitochondrial respiration, activation of cell-surface G-protein-coupled receptors, and protein acetylation by inhibiting histone deacetylases (HDACs). Butyrate (as sodium salt) added to drinking water was shown to improve pathological symptoms in numerous model mouse disorders, including models for cancer metastasis, neuroinflammation, autism spectrum disorders, dementia, insulin resistance, and colorectal cancer. Over 5000 PubMed-listed studies feature butyrate in their title, yet its genome-wide transcriptomic effects have not been reported in human cell lines from multiple healthy donors. Here, we report the genome-wide transcriptomic effects of 1 mM sodium butyrate on human lymphoblastoid cell lines (LCLs) generated from blood samples of eight unrelated healthy donors. Paired bioinformatics analysis comparing the butyrate-treated LCLs to the same untreated cell line identified thousands of differentially expressed gene (DEG) transcripts with padj<0.05, of which over half were upregulated by butyrate. Pathway analysis showed that butyrate exposure of LCLs upregulated extracellular matrix, cell adhesion, junction organization, Wnt signaling, axonogenesis, and neurodevelopment pathways. Downregulated pathways included cell cycle, G2/M checkpoint, E2F/MYC targets, DNA replication and repair, mitotic spindle integrity, mTOR signaling, oxidative phosphorylation, unfolded-protein response, and translation/ribosome-related pathways. Our RNA-seq study, utilizing LCLs from healthy donors and paired bioinformatic analysis, opens venues for assessing butyrate effects on cellular pathways and potential therapeutics for cancer, metabolic, immune, and CNS-related disorders.
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APA 7th
Volkov, H., Cohen, T., Shlayem, R., Shapira, E., Voinsky, I., Klin, H., et al. (2026). RNA-sequencing of butyrate-treated human lymphoblastoid cell lines shows dysregulated genes of multiple disease-related pathways. bioRxiv. https://doi.org/10.64898/2026.10.21.760620
Vancouver
Volkov H, Cohen T, Shlayem R, Shapira E, Voinsky I, Klin H, et al. RNA-sequencing of butyrate-treated human lymphoblastoid cell lines shows dysregulated genes of multiple disease-related pathways. bioRxiv. 2026. doi:10.64898/2026.10.21.760620.
BibTeX
@article{volkov2026-d5e3353a,
author = {Volkov, H. and Cohen, T. and Shlayem, R. and Shapira, E. and Voinsky, I. and Klin, H. and Grad, M. and Shomron, N. and others},
title = {{RNA-sequencing of butyrate-treated human lymphoblastoid cell lines shows dysregulated genes of multiple disease-related pathways}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.21.760620},
url = {https://doi.org/10.64898/2026.10.21.760620}
}
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Key findings
- Pathway analysis showed that butyrate exposure of LCLs upregulated extracellular matrix, cell adhesion, junction organization, Wnt signaling, axonogenesis, and neurodevelopment pathways.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it. We have no data on 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 multicenter collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | Laboratory or animal study (title names “cell lines”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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