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Open AccessVollständige AnalyseJun 21, 2026

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.

The question (PICO)
PopulationApoE−/− mice (n=36) with established MGD phenotype at 5 months of age; wild-type C57BL/6J controls (n=16)
InterventionTopical ocular sodium butyrate (SB) at 3 concentrations (1, 5, and 10 mM), administered for 3 weeks
VergleichTopical PBS (vehicle); wild-type mice as healthy controls
EndpunktCorneal fluorescein staining score, lacrimal inflammatory cytokines, meibomian gland and conjunctival histopathology, TLR4/MyD88/NF-κB signaling, OSM composition by 16S rRNA sequencing (V3–V4)
DEvidenz
Studie
In vitro study
Stichprobe
52
Effekt
Günstig
Dauer
3 Wochen
Zusammenfassung der Ergebnisse nach Endpunkt
EndpunktGradRichtungEffektStudien
Corneal fluorescein staining scoreD Günstigdirection favorable SB 5-10 mM vs PBS; in the quantitative effect size or 95% CI reported1
Ocular surface microbiome composition (diversity and relative abundance)D GünstigMuribacter muris increased, Staphylococcus lentus decreased in ApoE-/- vs WT; SB restored alterations; in the 95% CI or effect size reported1
TLR4/NF-κB p65 expression in meibomian glands and conjunctivaD Günstigdirection favorable SB vs PBS; in the quantitative effect size or 95% CI reported1
Lacrimal inflammatory cytokinesD Günstigdirection favorable SB vs PBS; in the quantitative effect size or 95% CI reported1
Tissue apoptosis (TUNEL) in meibomian glands and conjunctivaD Günstigdirection favorable SB vs PBS; in the quantitative effect size or 95% CI reported1
Meibomian gland histopathology (Oil Red O/PAS)D Günstigdirection favorable SB vs PBS; in the quantitative effect size or 95% CI reported1
Safety/toxicity of topical sodium butyrateD Neutralsafety confirmed at 1, 5, 10 mM in animal model; in the formal toxicity metric or 95% CI reported1
Corneal fluorescein staining scoreD
Richtung Günstig
Effektdirection favorable SB 5-10 mM vs PBS; in the quantitative effect size or 95% CI reported
Studien1
Ocular surface microbiome composition (diversity and relative abundance)D
Richtung Günstig
EffektMuribacter muris increased, Staphylococcus lentus decreased in ApoE-/- vs WT; SB restored alterations; in the 95% CI or effect size reported
Studien1
TLR4/NF-κB p65 expression in meibomian glands and conjunctivaD
Richtung Günstig
Effektdirection favorable SB vs PBS; in the quantitative effect size or 95% CI reported
Studien1
Lacrimal inflammatory cytokinesD
Richtung Günstig
Effektdirection favorable SB vs PBS; in the quantitative effect size or 95% CI reported
Studien1
Tissue apoptosis (TUNEL) in meibomian glands and conjunctivaD
Richtung Günstig
Effektdirection favorable SB vs PBS; in the quantitative effect size or 95% CI reported
Studien1
Meibomian gland histopathology (Oil Red O/PAS)D
Richtung Günstig
Effektdirection favorable SB vs PBS; in the quantitative effect size or 95% CI reported
Studien1
Safety/toxicity of topical sodium butyrateD
Richtung Neutral
Effektsafety confirmed at 1, 5, 10 mM in animal model; in the formal toxicity metric or 95% CI reported
Studien1

Kontext

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.

Was die Studie zeigte

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.

Wie es durchgeführt wurde

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.

Effektgröße

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.

Einschränkungen

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 der klinischen Praxis

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.

Was noch fehlt

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.

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