布拉氏酵母菌通过上调 METTL3,以 m6A 依赖性方式恢复肠道微生物群和代谢平衡,从而缓解过敏性哮喘。

IF 3.3 4区 医学 Q3 IMMUNOLOGY Immunology letters Pub Date : 2024-03-20 DOI:10.1016/j.imlet.2024.106853
Da Liu , Lang Hu , Yue Yang , Yina Wang , Yayong Li , Jing Su , Guyi Wang , Subo Gong
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引用次数: 0

摘要

背景:过敏性哮喘是一种异质性疾病,需要新的策略来预防或治疗这种疾病。研究表明,益生菌干预措施可有效预防哮喘。在此,我们研究了布拉氏酵母菌(S. boulardii)对卵清蛋白(OVA)诱导的小鼠过敏性哮喘的影响及其内在机制:方法:首先,我们利用OVA构建了小鼠哮喘模型,并给予布拉氏酵母菌干预。接下来,我们测量了肺损伤组织中的 N6-甲基腺苷(m6A)水平。16s rRNA用于鉴定粪便样本中不同的肠道微生物群。粪便中不同代谢物的分析是通过非靶向代谢组学进行的。利用皮尔逊相关系数分析了肠道微生物群、代谢物和甲基转移酶样 3(METTL3)之间的相关性。最后,我们收集了经OVA和布拉氏酵母菌干预处理的小鼠粪便,进行粪便微生物群移植(FMT)并干扰METTL3:结果:布拉氏酵母菌改善了哮喘小鼠的炎症和氧化应激,减轻了肺损伤。此外,布拉氏酵母菌还能调节哮喘小鼠的m6A修饰水平。16s rRNA测序显示布拉氏酵母菌重塑了哮喘小鼠的肠道微生物群平衡。非靶向代谢组学分析表明布拉氏酵母菌恢复了哮喘小鼠的代谢平衡。通过皮尔逊相关性分析,肠道微生物群、差异代谢物和METTL3之间存在相关性。此外,通过FMT和对METTL3的干扰,我们发现布拉氏酵母菌介导的肠道微生物群对METTL3的上调改善了哮喘小鼠的炎症和氧化应激,减轻了肺损伤:布拉氏酵母菌通过上调METTL3,以m6A依赖的方式恢复肠道微生物群和代谢平衡,从而缓解过敏性哮喘。
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Saccharomyces boulardii alleviates allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner

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.

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来源期刊
Immunology letters
Immunology letters 医学-免疫学
CiteScore
7.60
自引率
0.00%
发文量
86
审稿时长
44 days
期刊介绍: Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings. Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.
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