Background

Preterm infants frequently experience intermittent hypoxia (IH) episodes, rendering them susceptible to oxidative stress and gut dysbiosis. We tested the hypothesis that early supplementation with antioxidants and/or fish oil promotes gut biodiversity and mitigates IH-induced gut injury.

Methods

Newborn rats were exposed to neonatal IH from birth (P0) to P14 during which they received daily oral supplementation with: (1) coenzyme Q10 (CoQ10) in olive oil, (2) fish oil, (3) glutathione nanoparticles (nGSH), (4) CoQ10 + fish oil, or (5) olive oil (placebo control). Pups were placed in room air (RA) from P14 to P21 with no further treatment. RA controls were similarly treated. Stool samples were assessed for microbiota and terminal ileum for histopathology and morphometry, total antioxidant capacity, lipid peroxidation, and biomarkers of gut injury.

Results

Neonatal IH induced histopathologic changes consistent with necrotizing enterocolitis, which were associated with increased lipid peroxidation, toll-like receptor, transforming growth factor, and nuclear factor kappa B. Combination of CoQ10 + fish oil and nGSH were most effective for preserving gut integrity, reducing biomarkers of gut injury, and increasing commensal organisms.

Conclusions

Combination of antioxidants and fish oil may confer synergistic benefits to mitigate IH-induced injury in the terminal ileum.

Impact

• Antioxidant and fish oil (PUFA) co-treatment was most beneficial for reducing neonatal IH-induced gut injury.

• The synergistic effects of antioxidant and fish oil is likely due to prevention of IH-induced ROS attack on lipids, thus preserving and augmenting its therapeutic benefits.

• Combination treatment was also effective for increasing the abundance of the non-pathogenic Firmicutes phylum, which is associated with a healthy gastrointestinal system of the newborn.

• Extremely low gestational age neonates who are at high risk for frequent, repetitive neonatal IH and oxidative stress-induced diseases may benefit from this combination therapy.

中文翻译：

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新生儿间歇性缺氧、鱼油和/或抗氧化剂补充剂对新生大鼠肠道微生物群的影响

背景

早产儿经常经历间歇性缺氧 (IH) 发作，使他们容易受到氧化应激和肠道菌群失调的影响。我们验证了早期补充抗氧化剂和/或鱼油可促进肠道生物多样性并减轻 IH 引起的肠道损伤的假设。

方法

新生大鼠从出生 (P0) 到 P14 暴露于新生 IH，在此期间它们每天口服补充：(1) 橄榄油中的辅酶 Q10 (CoQ10)，(2) 鱼油，(3) 谷胱甘肽纳米粒子 (nGSH)， (4) CoQ10 + 鱼油，或 (5) 橄榄油（安慰剂对照）。从 P14 到 P21 将幼犬置于室内空气 (RA) 中，无需进一步处理。对 RA 对照组进行了类似处理。评估粪便样本的微生物群和回肠末端的组织病理学和形态计量学、总抗氧化能力、脂质过氧化和肠道损伤的生物标志物。

结果

新生儿 IH 引起的组织病理学变化与坏死性小肠结肠炎一致，这与脂质过氧化、toll 样受体、转化生长因子和核因子 kappa B 增加有关。辅酶 Q10 + 鱼油和 nGSH 的组合对于保持肠道完整性最有效，减少肠道损伤的生物标志物和增加的共生生物。

结论

抗氧化剂和鱼油的组合可能会产生协同作用，以减轻 IH 引起的回肠末端损伤。

影响

• 抗氧化剂和鱼油 (PUFA) 联合治疗对减少新生儿 IH 引起的肠道损伤最有益。

• 抗氧化剂和鱼油的协同作用可能是由于防止了 IH 诱导的 ROS 对脂质的攻击，从而保持和增强了其治疗益处。

• 联合治疗对于增加与新生儿健康胃肠系统相关的非致病性厚壁菌门的丰度也是有效的。

• 极低胎龄新生儿可能会从这种联合治疗中受益，这些新生儿具有频繁、重复性新生儿 IH 和氧化应激诱发疾病的高风险。