Ozone Hydrotherapy Improves Seborrheic Dermatitis by Regulating Scalp Microbiome and Mitochondrial Lactate Shuttle in Keratinocytes

Abstract Background Seborrheic dermatitis (SD) is characterized by limited therapeutic options and high recurrence rates, and the efficacy and mechanism of ozone hydrotherapy for SD remain unclear, especially its potential role in regulating metabolic pathways of keratinocytes. Methods We performed a single-arm, open-label, self-controlled before-and-after study of ozone hydrotherapy in 24 SD patients, evaluating clinical symptoms and analyzing scalp microbiome. A Malassezia-induced guinea pig model of SD-like lesions and a Malassezia-infected HaCaT cell model were used to explore barrier repair, anti-inflammatory effects and the potential involvement of mitochondrial lactate shuttle. Results Ozone hydrotherapy significantly alleviated erythema, scaling and pruritus during the 3-week treatment period in SD patients. Treatment was well tolerated with no serious adverse events observed. It decreased the abundance of Malassezia and Staphylococcus, increased skin microbial Shannon diversity, and reshaped the structure of scalp fungal and bacterial communities. In guinea pigs, ozone water upregulated barrier-related genes and suppressed inflammatory cytokines. In HaCaT cells, ozone water restored mitochondrial lactate shuttle function, reversed the abnormal expression and localization of MCT1, MCT4 and LDHB, reduced lactate accumulation and pro-inflammatory factor release. Conclusion Ozone hydrotherapy may improve SD symptoms by regulating scalp microbial homeostasis, mechanistic studies further suggest that it may alleviate inflammation by reversing Malassezia-induced mitochondrial lactate shuttle abnormalities in keratinocytes. Ozone hydrotherapy represents a promising candidate intervention for SD symptom management, pending validation in controlled clinical trials.