Abstract

Autoinducer-2 (AI-2) has a widely accepted role in bacterial intra- and interspecies communication. Little is known about the relationships between AI-2 and NEC. This study found that AI-2 levels in patients and in a NEC mouse model were detected using the Vibrio harveyi BB170 assay system. Bacterial communities of the newborns' stool microbiota (NEC acute group, NEC recovery group, control group, and antibiotics-free group) and of the NEC mouse model (NEC group and control group) were detected by high-throughput sequencing. Intestinal histopathological changes were observed after HE staining. The AI-2 level in the NEC acute group (44.75 [40.17~65.52]) was significantly lower than that in the control group, NEC recovery group and antibiotics-free group. The overall microbiota compositions of each group at the phylum level were not significantly different. The proportions of Enterococcus, Clostridium_sensu_stricto_1, Peptoclostridium, and Veillonella had significant differences among the 4 groups at the genus level. In animal experiments, the AI-2 level in feces of NEC mice (56.89 ± 11.87) was significantly lower than that in the feces of control group mice (102.70 ± 22.97). The microbiota compositions of NEC and control group mice at the phylum level were not significantly different. At the genus level, Klebsiella, Clostridium_sensu_stricto_1, and Peptoclostridium abundances in the NEC group increased significantly compared with those in the control group (P < 0.05). In addition, Lactobacillus, Pasteurella, and Parabacteroides abundances in the NEC group decreased significantly compared with those in the normal control group (P < 0.05), while Lactobacillus, Pasteurella, and Parabacteroides abundances had the opposite trend. The AI-2 concentration decreased significantly in the acute phase of NEC and increased gradually in the convalescent phase. We conclude that the concentration of AI-2 was correlated with intestinal flora disorder and different stages of disease. AI-2 may be a new biomarker for the diagnosis and monitoring of NEC.Trial Registry: ClinicalTrials.gov; ChiCTR-ROC-17013746; URL: www.clinicaltrials.gov

Highlights

  • Necrotizing enterocolitis (NEC) is a serious neonatal intestinal disease that most frequently affects preterm infants

  • No significant differences in the mode of delivery, type of feeding, gestational age, and gender ratio were noted between the NEC group and the control group

  • Our study further revealed that AI-2 was significantly associated with the occurrence and recovery of NEC and that the level of AI-2 in NEC patients in the acute stage was lower than that in the controls and NEC patients in the recovery stage

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Summary

Introduction

Necrotizing enterocolitis (NEC) is a serious neonatal intestinal disease that most frequently affects preterm infants. NEC reportedly affects ∼10% of all premature infants (Hackam et al, 2018). Neonatal care has evolved greatly over time, but despite improvements in ventilation, nutrition, and temperature regulation, NEC remains a leading cause of death from gastrointestinal disease (Warner et al, 2016). Neonates often present with obvious clinical signs, the diagnosis of NEC can be subtle and insidious. NEC in newborns often develops rapidly and is difficult to detect early due to a lack of specific biomarkers. Identifying a new biomarker for the diagnosis and monitoring of NEC that is non-invasive, non-radiative, inexpensive, and rapid is an important endeavor

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