Topical sodium butyrate modulates ocular surface microbiome and reduces meibomian gland dysfunction inflammation in ApoE−/− mice
In a murine model of meibomian gland dysfunction, topical sodium butyrate (5–10 mM) favored reduction of inflammatory markers and ocular surface microbiome modulation, with no human efficacy data available.
| Outcome | Grade | Direction | Effect | Studies |
|---|---|---|---|---|
| Corneal fluorescein staining score | D | ▲ Favorable | direction favorable SB 5-10 mM vs PBS; in the quantitative effect size or 95% CI reported | 1 |
| Ocular surface microbiome composition (diversity and relative abundance) | D | ▲ Favorable | Muribacter muris increased, Staphylococcus lentus decreased in ApoE-/- vs WT; SB restored alterations; in the 95% CI or effect size reported | 1 |
| TLR4/NF-κB p65 expression in meibomian glands and conjunctiva | D | ▲ Favorable | direction favorable SB vs PBS; in the quantitative effect size or 95% CI reported | 1 |
| Lacrimal inflammatory cytokines | D | ▲ Favorable | direction favorable SB vs PBS; in the quantitative effect size or 95% CI reported | 1 |
| Tissue apoptosis (TUNEL) in meibomian glands and conjunctiva | D | ▲ Favorable | direction favorable SB vs PBS; in the quantitative effect size or 95% CI reported | 1 |
| Meibomian gland histopathology (Oil Red O/PAS) | D | ▲ Favorable | direction favorable SB vs PBS; in the quantitative effect size or 95% CI reported | 1 |
| Safety/toxicity of topical sodium butyrate | D | — Neutral | safety confirmed at 1, 5, 10 mM in animal model; in the formal toxicity metric or 95% CI reported | 1 |
Context
Meibomian gland dysfunction (MGD) is the leading cause of evaporative dry eye disease, with a global prevalence of 35.8%. The causal role of the ocular surface microbiome (OSM) in MGD remains undefined. Interventions modulating OSM and local inflammation are biologically plausible but lack clinical validation.
What the study showed
ApoE−/− mice developed clinical and histological MGD features with OSM dysbiosis (increased Proteobacteria, decreased Bacteroidota; increased Muribacter muris, decreased Staphylococcus lentus). SB at 5 and 10 mM improved corneal fluorescein staining scores versus PBS. SB reduced TLR4, NF-κB p65, and inflammatory cytokine expression in meibomian glands and conjunctiva, and reduced tissue apoptosis. Absolute effect sizes, 95% CIs, and quantitative effect measures were not reported in the available text.
How it was done
Controlled in vivo experimental study using ApoE−/− mice as MGD models and C57BL/6J as healthy controls. Intervention duration: 3 weeks. OSM analyzed by 16S rRNA sequencing (V3–V4); inflammation assessed by RT-qPCR, immunohistochemistry, Western blot, and lacrimal cytokine ELISA; histopathology by Oil Red O, PAS, and TUNEL staining.
Effect magnitude
The study does not report effect sizes with 95% CI or absolute numerical differences for primary outcomes; effect magnitude cannot be quantified from the available text.
Limitations
Animal model (ApoE−/− mouse) with unestablished translational validity for human MGD; absence of 95% CIs and explicit effect sizes; small samples (n=36 MGD, n=16 controls) without reported power calculation; no germ-free depletion group to allow causal inference between dysbiosis and inflammation; SYRCLE risk of bias tool for animal studies not applied; 3-week follow-up limits conclusions on durability.
In clinical practice
The data do not support clinical use of topical sodium butyrate for MGD in humans. The study is exploratory and confined to a murine model. Clinicians should not alter clinical practice based on these results.
What is still missing
Human RCTs assessing safety, tolerability, and efficacy of topical SB in MGD patients. Mechanistic studies with germ-free models to establish causality between OSM alterations and MGD inflammation.