Autoinducer-2 May Be a New Biomarker for Monitoring Neonatal Necrotizing Enterocolitis

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.

Exogenous Autoinducer-2 Rescues Intestinal Dysbiosis and Intestinal Inflammation in a Neonatal Mouse Necrotizing Enterocolitis Model

“…This finding was consistent with a meta-analysis of fecal microorganisms in NEC preterm infants (Pammi et al, 2017). At the genus level, we also found that the abundance levels of Clostridium_sensu_stricto_1 were significantly increased, and previous studies also found that Clostridium_sensu_stricto_1 is much more abundant in NEC infants (Fu et al, 2020). The proliferation of Clostridium species in the colon may produce toxins and lead to intestinal epithelial damage (Schönherr-Hellec and Aires, 2019).…”

“…AI-2 levels were reduced in the acute stage and increased in the recovery stage of NEC. The AI-2 concentration inversely correlates with the degree of inflammation and microbial dysbiosis in NEC (Fu et al, 2020). In the present study, a similar phenomenon was observed in the mouse NEC model (Figure 3).…”

“…Artificially increasing the level of AI-2 can attenuate antibiotic-induced intestinal dysbiosis, which plays an important role in the development of NEC (Sun et al, 2015). We have previously reported that the AI-2 concentration decreases significantly in the acute phase of NEC and increases gradually in the recovery phase of NEC (Fu et al, 2020). These findings illustrate that AI-2 may be an important target for the correction of intestinal flora imbalance.…”

“…The methods have been previously described (Fu et al, 2020). The ileum and colon of each mouse were irrigated with 400 ml of 2216E liquid medium, and the contents were gathered with sterile tubes, vortexed and centrifuged.…”

“…Fecal microbiota genomic DNA was extracted with a QIAamp FAST DNA Stool Mini-Kit (Qiagen, Germany) according to the manufacturer's instructions, as previously described (Fu et al, 2020). The DNA extracts were detected on 1% agarose gels, and the DNA concentration and purity were assessed with a spectrophotometer (NanoDrop 2000 UV-vis, Thermo Scientific, USA).…”