Saccharomyces boulardii alleviates allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner

•Probiotics play a vital role in regulating gut microbiota and metabolism to alleviate asthma.•S. boulardii alleviated allergic asthma in an m6A-dependent manner by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3.•S. boulardii ameliorated inflammation and oxidative stress and alleviated lung injury in asthmatic mice by establishing an asthma mouse model. Allergic asthma is a heterogeneous disease and new strategies are needed to prevent or treat this disease. Studies have shown that probiotic interventions are effective in preventing asthma. Here, we investigated the impact of Saccharomyces boulardii (S. boulardii) on ovalbumin (OVA)-induced allergic asthma in mice, as well as the underlying mechanisms. First, we constructed a mouse asthma model using OVA and given S. boulardii intervention. Next, we measured N6-methyladenosine (m6A) levels in lung injury tissues. 16 s rRNA was employed to identify different gut microbiota in fecal samples. The analysis of differential metabolites in feces was performed by non-targeted metabolomics. Pearson correlation coefficient was utilized to analyze correlation between gut microbiota, metabolites and methyltransferase-like 3 (METTL3). Finally, we collected mouse feces treated by OVA and S. boulardii intervention for fecal microbiota transplantation (FMT) and interfered with METTL3. S. boulardii improved inflammation and oxidative stress and alleviated lung damage in asthmatic mice. In addition, S. boulardii regulated m6A modification levels in asthmatic mice. 16 s rRNA sequencing showed that S. boulardii remodeled gut microbiota homeostasis in asthmatic mice. Non-targeted metabolomics analysis showed S. boulardii restored metabolic homeostasis in asthmatic mice. There was a correlation between gut microbiota, differential metabolites, and METTL3 analyzed by Pearson correlation. Additionally, through FMT and interference of METTL3, we found that gut microbiota mediated the up-regulation of METTL3 by S. boulardii improved inflammation and oxidative stress in asthmatic mice, and alleviated lung injury. S. boulardii alleviated allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.