维生素A缺乏抑制CEACAM1,通过降低微生物衍生的短链脂肪酸的调节,损害结肠上皮质屏障功能
Junyan Yan1, Lu Xiao1,2, Di Feng1
1Children Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Nutrition and Health, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing 401122, China.
维生素A缺乏通过减少有益的短链脂肪酸 (SCFA) 来损害肠道屏障功能. 产后维生素A补充剂和丁酸盐可以恢复肠道屏障的完整性,突出了与怀孕有关的VAD的潜在干预措施.
科学领域:
- 微生物学 微生物学
- 营养科学 营养科学
- 胃肠病学 胃肠病学
背景情况:
- 维生素A (VA) 对肠道微生物群和屏障功能至关重要.
- 短链脂肪酸 (SCFA) 保护肠道屏障,但在VA缺乏症 (VAD) 中会减少.
- 需要了解SCFA在VAD引起的结肠壁障碍中的作用.
研究的目的:
- 调查SCFA如何调节VAD中的结肠上皮屏障完整性.
- 在怀孕期间识别特定的SCFA和与VAD相关的细菌变化.
- 探索将VAD,SCFA和肠道屏障功能障碍联系在一起的分子机制.
主要方法:
- 在怀孕期间对VAD和正常VA大鼠 (VAN) 的比较.
- 对结肠脱体结节,SCFA水平和细菌丰度的分析.
- RNA测序以识别与肠道屏障和基因素脱乙酶复合体相关的差异表达基因.
- 使用Caco-2细胞进行体外研究,以评估丁酸盐对CEACAM1表达的作用.
主要成果:
- 由于SCFA产生细菌的减少,VAD损害了结肠的desmosome连接,并降低了SCFA水平 (乙酸盐,酸盐,丁酸盐).
- 在结肠中,VAD导致了下调的CEACAM1和上调的HDAC1/HDAC3表达.
- 在产后早期服用VA补充剂可以挽救这些VAD诱导的变化.
- 在Caco-2细胞中,丁酸盐治疗抑制了CEACAM1促进体上的HDAC3丰富,增加了CEACAM1的表达.
结论:
- 酸盐干预可以减轻由VAD引起的结肠屏障功能障碍.
- 及时的产后VA干预可以扭转与怀孕相关的VAD对肠道屏障完整性的损害.
- 这项研究阐明了SCFA和基因素脱乙酶在VAD诱导的肠道屏障损伤中的作用.
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