肠道微生物脂调节肠道基因表达,可以抵消抗生素治疗的影响
Martin Blaser1, Xue-Song Zhang2, Meifan Zhang2
1Rutgers University.
Research square
|December 11, 2025
概括
早期接触抗生素会破坏肠道细菌脂质,增加1型糖尿病的风险. 特定的脂可以恢复肠道健康和免疫力,为炎症性疾病提供治疗潜力.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 代谢学 代谢学 代谢学
背景情况:
- 早期暴露于抗生素会破坏肠道微生物群,从而增加患1型糖尿病 (T1D) 等免疫疾病的风险.
- 肠道微生物产生的脂质 (GMPL) 是肠道环境的关键组成部分,但它们在抗生素诱导的免疫失调中的作用尚不清楚.
研究的目的:
- 为了研究抗生素暴露对肠道脂质概况的影响.
- 为了确定参与免疫调节和代谢功能的特定GMPLs.
- 在T1D小鼠模型中评估已识别的GMPLs的治疗潜力.
主要方法:
- 在无细菌,常规和抗生素治疗的小鼠中对肠道脂质特征进行比较分析.
- 特定脂 (LPG和PG) 的识别和结构定义.
- 功能性测试评估对NFkB激活,先天免疫和上皮细胞代谢的影响.
- 对抗生素治疗的非肥胖糖尿病 (NOD) 小鼠进行脂治疗.
主要成果:
- 抗生素治疗改变了小鼠和人类的GMPL概况,在微生物群移植后部分恢复.
- 确定了四种特定的脂 (LPG(13:0),LPG(16:0),LPG(18:0),PG(15:0_15:0)) 并进行了功能性特征.
- 这些脂抑制了LPS诱导的NFkB激活,调节了免疫基因表达,并增强了线粒体呼吸.
- 口服LPG ((16:0) 或LPG ((18:0) 给接受抗生素治疗的NOD小鼠,部分恢复了肠道微生物群,正常化了质基因表达,并改善了上皮功能.
结论:
- 细菌脂作为肠道免疫和宿主新陈代谢的关键调节者.
- 恢复特定的GMPL可能为抗生素诱导的免疫失调和T1D等相关疾病提供治疗策略.
- 这项研究突出了肠道微生物群,其代谢物和宿主免疫恒温之间的复杂关系.
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