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

Da Liu; Lang Hu; Yue Yang; Yina Wang; Yayong Li; Jing Su; Guyi Wang; Subo Gong

doi:10.1016/j.imlet.2024.106853

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

Immunol Lett. 2024 Mar 20:267:106853. doi: 10.1016/j.imlet.2024.106853. Online ahead of print.

Authors

Da Liu¹, Lang Hu², Yue Yang², Yina Wang², Yayong Li³, Jing Su², Guyi Wang⁴, Subo Gong⁵

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, 410004, Hunan, China.
² Department of Geriatrics, The Second Xiangya Hospital Central South University, Changsha, 410011, Hunan, China.
³ Department of Emergency, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
⁴ Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
⁵ Department of Geriatrics, The Second Xiangya Hospital Central South University, Changsha, 410011, Hunan, China. Electronic address: gsb510@csu.edu.cn.

PMID: 38513836
DOI: 10.1016/j.imlet.2024.106853

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: S. boulardii alleviated allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.

Keywords: Gut microbiota; M6a, Allergic asthma; Metabolic homeostasis; Saccharomyces boulardii.