Neonatology directorate, King Edward Memorial Hospital for Women Perth, Subiaco, Western Australia, Australia
Faculty of Science, University of New South Wales, Sydney, New South Wales, Australia.
BMJ Open Gastroenterol. 2022 Feb;9(1). doi: 10.1136/bmjgast-2021-000811.
OBJECTIVE: Evidence indicates that multistrain probiotics benefit preterm infants more than single-strain (SS) probiotics. We assessed the effects of SS versus triple-strain (TS) probiotic supplementation (PS) in extremely preterm (EP) infants. DESIGN: EP infants (gestational age (GA) <28 weeks) were randomly allocated to TS or SS probiotic, assuring blinding. Reference (REF) group was EP infants in the placebo arm of our previous probiotic trial. PS was commenced with feeds and continued until 37 weeks' corrected GA. Primary outcome was time to full feed (TFF: 150 mL/kg/day). Secondary outcomes included short-chain fatty acids and faecal microbiota collected at T1 (first week) and T2 (after 3 weeks of PS) using 16S ribosomal RNA gene sequencing. RESULTS: 173 EP (SS: 86, TS: 87) neonates with similar GA and birth weight (BW) were randomised. Median TFF was comparable (11 (IQR 8-16) vs 10 (IQR 8-16) days, p=0.92). Faecal propionate (SS, p<0.001, and TS, p=0.0009) and butyrate levels (TS, p=0.029) were significantly raised in T2 versus T1 samples. Secondary clinical outcomes were comparable. At T2, alpha diversity was comparable (p>0.05) between groups, whereas beta-diversity analysis revealed significant differences between PS and REF groups (both p=0.001). Actinobacteria were higher (both p<0.01), and Proteobacteria, Firmicutes and Bacteroidetes were lower in PS versus REF. Gammaproteobacteria, Clostridia and Negativicutes were lower in both PS versus REF. CONCLUSION: TFF in EP infants was similar between SS and TS probiotics. Both probiotics were effective in reducing dysbiosis (higher bifidobacteria and lower Gammaproteobacteria). Long-term significance of increased propionate and butyrate needs further studies. TRIAL REGISTRATION NUMBER: ACTRN 12615000940572.
目的：有证据表明，多菌株益生菌比单菌株（SS）益生菌更有益于早产儿。我们评估了 SS 与三菌株（TS）益生菌补充剂（PS）在极早产儿（EP）中的作用。
设计：将 EP 婴儿（胎龄（GA）<28 周）随机分配到 TS 或 SS 益生菌组，并确保双盲。参考（REF）组为我们之前益生菌试验中安慰剂组的 EP 婴儿。PS 随喂养开始，并持续至校正 GA 37 周。主要结局是达到全喂养的时间（TFF：150 mL/kg/天）。次要结局包括使用 16S 核糖体 RNA 基因测序在 T1（第 1 周）和 T2（PS 后 3 周）收集短链脂肪酸和粪便微生物群。
结果：173 名 EP（SS：86，TS：87）新生儿具有相似的 GA 和出生体重（BW），进行了随机分组。中位数 TFF 无差异（11（IQR 8-16）与 10（IQR 8-16）天，p=0.92）。T2 时粪便丙酸（SS，p<0.001，TS，p=0.0009）和丁酸水平（TS，p=0.029）明显升高。次要临床结局相似。T2 时，两组间 alpha 多样性无差异（p>0.05），而 PS 和 REF 组间 beta 多样性分析显示出显著差异（均 p=0.001）。PS 组中放线菌较高（均 p<0.01），而 PS 组中厚壁菌门、拟杆菌门和变形菌门较低。PS 组中γ变形菌门、梭菌和 Negativicutes 较低。
结论：SS 和 TS 益生菌在 EP 婴儿中的 TFF 无差异。两种益生菌均能有效减少肠道菌群失调（双歧杆菌增加，γ变形菌减少）。增加丙酸和丁酸的长期意义需要进一步研究。
试验注册号：ACTRN 12615000940572。
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