Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
Sci Transl Med. 2023 May 3;15(694):eadg5562. doi: 10.1126/scitranslmed.adg5562.
Bacterial bloodstream infections (BSIs) resulting in late-onset sepsis affect up to half of extremely preterm infants and have substantial morbidity and mortality. Bacterial species associated with BSIs in neonatal intensive care units (NICUs) commonly colonize the preterm infant gut microbiome. Accordingly, we hypothesized that the gut microbiome is a reservoir of BSI-causing pathogenic strains that increase in abundance before BSI onset. We analyzed 550 previously published fecal metagenomes from 115 hospitalized neonates and found that recent ampicillin, gentamicin, or vancomycin exposure was associated with increased abundance of Enterobacteriaceae and Enterococcaceae in infant guts. We then performed shotgun metagenomic sequencing on 462 longitudinal fecal samples from 19 preterm infants (cases) with BSI and 37 non-BSI controls, along with whole-genome sequencing of the BSI isolates. Infants with BSI caused by Enterobacteriaceae were more likely than infants with BSI caused by other organisms to have had ampicillin, gentamicin, or vancomycin exposure in the 10 days before BSI. Relative to controls, gut microbiomes of cases had increased relative abundance of the BSI-causing species and clustered by Bray-Curtis dissimilarity according to BSI pathogen. We demonstrated that 11 of 19 (58%) of gut microbiomes before BSI, and 15 of 19 (79%) of gut microbiomes at any time, harbored the BSI isolate with fewer than 20 genomic substitutions. Last, BSI strains from the Enterobacteriaceae and Enterococcaceae families were detected in multiple infants, indicating BSI-strain transmission. Our findings support future studies to evaluate BSI risk prediction strategies based on gut microbiome abundance in hospitalized preterm infants.
导致晚发性败血症的细菌性血流感染（BSI）影响多达一半的极早产儿，且具有较高的发病率和死亡率。与新生儿重症监护病房（NICU）BSI 相关的细菌物种通常定植于早产儿肠道微生物组。因此，我们假设肠道微生物组是 BSI 致病菌株的储库，这些菌株在 BSI 发病前丰度增加。我们分析了 115 名住院新生儿的 550 份先前发表的粪便宏基因组，发现最近使用氨苄西林、庆大霉素或万古霉素与婴儿肠道中肠杆菌科和肠球菌科的丰度增加有关。然后，我们对 19 名患有 BSI 的早产儿（病例）和 37 名非 BSI 对照的 462 份纵向粪便样本进行了 shotgun 宏基因组测序，并对 BSI 分离株进行了全基因组测序。与其他生物体引起的 BSI 相比，由肠杆菌科引起的 BSI 的婴儿更有可能在 BSI 前 10 天内接受氨苄西林、庆大霉素或万古霉素治疗。与对照组相比，病例的肠道微生物组中导致 BSI 的物种相对丰度增加，根据 BSI 病原体按 Bray-Curtis 不相似性聚类。我们证明，在 BSI 之前，19 个病例中有 11 个（58%），在任何时间点，19 个病例中有 15 个（79%）的肠道微生物组中都存在 BSI 分离株，其基因组替换数少于 20 个。最后，在多个婴儿中检测到肠杆菌科和肠球菌科的 BSI 菌株，表明存在 BSI 菌株传播。我们的研究结果支持未来的研究，以评估基于住院早产儿肠道微生物组丰度的 BSI 风险预测策略。
