A recent study published in the Journal of Otology (November 2025) by researchers from Tongji Medical College and affiliated hospitals has identified that a deficiency in SIRT3, a mitochondrial regulator, worsens eustachian tube dysfunction during acute middle-ear infection in mice. The research focused on the effects of lipopolysaccharide (LPS), a component commonly used to model bacterial inflammation, and its impact when SIRT3 is absent.
The study found that mice lacking SIRT3 experienced more severe dysfunction after LPS-induced acute otitis media. Detailed imaging and functional tests revealed that these mice developed thicker mucus, weaker cilia, and impaired opening of the eustachian tube compared to normal mice. This led to increased tissue vulnerability and greater difficulty in pressure regulation within the ear.
When comparing wild-type with SIRT3-knockout mice, both groups had similar eustachian tube structures before inflammation. However, after LPS injection, significant differences emerged. Mice without SIRT3 showed increased goblet-cell proliferation, more mucus plugs, and higher levels of MUC5AC expression—factors associated with denser and stickier mucus. Scanning electron microscopy confirmed greater shortening and loss of epithelial cilia in these mice.
Functional assessments indicated that SIRT3-deficient mice required higher passive opening pressure for their eustachian tubes after LPS treatment, showing increased resistance to tube opening. Although neither SIRT3 deficiency nor LPS alone caused a notable decrease in mucociliary clearance, together they resulted in a marked reduction in transport distance. These mice also struggled more with clearing negative pressure under baseline conditions.
According to the research team: "The eustachian tube may appear structurally simple, but its function relies on a delicate interplay of mucus properties, ciliary motion, and pressure-balancing mechanics. Our findings show that SIRT3 acts as a stabilizing force during inflammation. When this mitochondrial regulator is absent, the system loses its resilience-mucus becomes heavier, clearance slows, and pressure equalization becomes more difficult. Understanding this protective role helps explain why certain individuals are more prone to chronic or recurrent ear infections and may guide new therapeutic strategies."
The study suggests that therapies aimed at increasing SIRT3 activity or targeting related pathways could help restore mucociliary function and improve recovery from infection-related inflammation. Because issues like excessive MUC5AC production and ciliary impairment are also seen in respiratory diseases, these findings may have broader implications beyond ear health.
The authors propose that improving mitochondrial resilience through such interventions could lead to better clinical outcomes for patients with persistent middle-ear or airway conditions.
