背景:增强我们对医疗干预对微生物组的潜在影响的理解,早产婴儿的耐药性和分枝杆菌组具有推进感染预防和治疗策略的巨大潜力。我们进行了一项前瞻性准干预研究,以更好地了解抗生素,和益生菌,和其他医学因素影响早产儿的肠道发育。平行进行了受控的新生小鼠模型,旨在密切反映和预测曝光。将早产儿和新生小鼠分为四组:仅使用抗生素,只有益生菌,抗生素,然后是益生菌,这些干预都没有。在不同的时间点收集早产儿和新生小鼠的粪便样本,并通过16SrRNA扩增子测序进行分析。ITS扩增子测序和全基因组鸟枪测序。
结果:人类婴儿微生物组显示出出乎意料的高度异质性。观察到医疗暴露(抗生素/益生菌)对菌株模式的影响很小,然而,双歧杆菌在暴露于益生菌后被发现更丰富,不管以前的抗生素给药。在抗性组中鉴定了27个抗生素抗性基因。在不同的治疗组中,高的内变异性是明显的。最后,我们发现抗生素和益生菌对早产儿的分枝杆菌组具有显著影响,但对早产儿的微生物组和耐药性没有显著影响.
结论:尽管我们的分析显示了短暂的影响,这些结果为继续研究医学干预对微生物组的影响提供了积极的动力,早产儿的耐药性和分枝杆菌。
BACKGROUND: Enhancing our understanding of the underlying influences of medical interventions on the microbiome, resistome and mycobiome of preterm born infants holds significant potential for advancing infection prevention and treatment strategies. We conducted a prospective quasi-intervention study to better understand how antibiotics, and probiotics, and other medical factors influence the gut development of preterm infants. A controlled neonatal mice model was conducted in parallel, designed to closely reflect and predict exposures. Preterm infants and neonatal mice were stratified into four groups: antibiotics only, probiotics only, antibiotics followed by probiotics, and none of these interventions. Stool samples from both preterm infants and neonatal mice were collected at varying time points and analyzed by 16 S rRNA amplicon sequencing, ITS amplicon sequencing and whole genome shotgun sequencing.
RESULTS: The human infant microbiomes showed an unexpectedly high degree of heterogeneity. Little impact from medical exposure (antibiotics/probiotics) was observed on the strain patterns, however, Bifidobacterium bifidum was found more abundant after exposure to probiotics, regardless of prior antibiotic administration. Twenty-seven antibiotic resistant genes were identified in the resistome. High intra-variability was evident within the different treatment groups. Lastly, we found significant effects of antibiotics and probiotics on the mycobiome but not on the microbiome and resistome of preterm infants.
CONCLUSIONS: Although our analyses showed transient effects, these results provide positive motivation to continue the research on the effects of medical interventions on the microbiome, resistome and mycobiome of preterm infants.