Lee Chien-Chung, Feng Ye, Yeh Yuan-Ming, Lien Reyin, Chen Chyi-Liang, Zhou Ying-Li, Chiu Cheng-Hsun
Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Sir Run Run Shaw Hospital, Institute for Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Front Microbiol. 2021 Oct 7;12:746111. doi: 10.3389/fmicb.2021.746111. eCollection 2021.
Gut dysbiosis may precede neonatal sepsis, but the association is still not well-understood. The goal of this study is to investigate the association between gut microbiota and neonatal sepsis, and to seek the evidence of colonization of pathogenic bacteria in the gut before evolving into an invasive infection. A prospective cohort study examined fecal microbiota composition in preterm infants with and without sepsis. Thirty-two very-low-birth-weight (VLBW) preterm infants and 10 healthy term infants as controls were enrolled. The fecal samples collected from the participants at the first, fourth, and seventh weeks of life underwent 16S rRNA amplicon sequencing for measurement of the diversity and composition of the microbiota. The bacterial isolates causing neonatal sepsis were genome sequenced. PCR was performed to confirm the translocation of the bacteria from the gut to the blood. The results showed that VLBW preterm infants with sepsis had lower microbial diversity in the gut at birth compared to preterm infants without sepsis and term infants. The composition of gut microbiome in preterm infants was similar to healthy terms at birth but evolved toward dysbiosis with increasing and decreasing weeks later. The strain-specific PCR confirmed the presence of causative pathogens in the gut in 4 (40%) out of 10 VLBW preterms with sepsis before or at onset of sepsis, and persistence of the colonization for weeks after antibiotic treatment. The same bacterial strain could horizontally spread to cause infection in other infants. Prolonged antibiotic exposure significantly reduced beneficial and in the gut. In conclusion, preterm infants with gut dysbiosis are at risk for neonatal sepsis, and the causative pathogens may be from the gut and persist to spread horizontally. The association of increased abundance and decrease in microbiome diversity suggests the need for interventions targeting the gut microbiome to prevent dysbiosis and sepsis in VLBW preterm infants.
肠道菌群失调可能先于新生儿败血症出现，但二者之间的关联仍未得到充分理解。本研究的目的是调查肠道微生物群与新生儿败血症之间的关联，并寻找致病菌在肠道定植后发展为侵袭性感染的证据。一项前瞻性队列研究检查了患有和未患有败血症的早产儿的粪便微生物群组成。招募了32名极低出生体重（VLBW）早产儿和10名健康足月儿作为对照。在生命的第一周、第四周和第七周从参与者收集的粪便样本进行16S rRNA扩增子测序，以测量微生物群的多样性和组成。对导致新生儿败血症的细菌分离株进行全基因组测序。进行PCR以确认细菌从肠道向血液的转移。结果显示，与未患败血症的早产儿和足月儿相比，患败血症的VLBW早产儿出生时肠道微生物多样性较低。早产儿出生时肠道微生物组的组成与健康足月儿相似，但在数周后随着时间推移向失调状态演变。菌株特异性PCR证实，在10名患败血症的VLBW早产儿中，有4名（40%）在败血症发生前或发生时肠道中存在致病病原体，并且在抗生素治疗后数周内持续定植。同一菌株可水平传播导致其他婴儿感染。长期接触抗生素会显著减少肠道中的有益菌。总之，肠道失调的早产儿有患新生儿败血症的风险，致病病原体可能来自肠道并持续水平传播。有益菌丰度增加和微生物组多样性降低之间的关联表明，需要针对肠道微生物组进行干预，以预防VLBW早产儿的失调和败血症。
