Abstract: Objective To investigate the effect of different modes of delivery and the use of antibiotics on the development and treatment of neonatal hyperbilirubinemia from microecological perspective.Methods Totally 90 cases of neonates with hyperbilirubinemia admitted to the hospital from January to December 2021 were selected. They were divided into natural birth group and cesarean section group according to the mode of delivery, and were divided into cefodizime group, cefoxitin group and control group (no antibiotics) according to the use of antibiotics. There were 40 newborns in the normal control group in the same period in the obstetric department. To analyze the distribution characteristics of intestinal microbiota in neonates with hyperbilirubinemia in different modes of delivery and with different antibiotics,  and to compare the changes in the metabolites of the intestinal microbiota in neonates with hyperbilirubinemia after the use of different antibiotics.Results Comparison of the intestinal microbiota of neonates with hyperbilirubinemia in the cesarean section group and natural birth group showed a statistically significant difference(P<0.05). There was a positive correlation between Carnobacterium,  Odoribacter and hyperbilirubinemic neonates in the natural birth group(P<0.05), and a positive correlation between unclassified Enterobacteriaceae and hyperbilirubinemic neonates in the cesarean section group(P<0.05). The intestinal microbiota of hyperbilirubinemia neonates in cefodizime group,  cefoxitin group and control group was significantly different(P<0.05). Bifidobacterium was negatively correlated (P<0.05) with hyperbilirubinemic neonates in the cefodizine and cefoxitin groups, Enterococcus, Lactobacillus and Carnobacterium were negatively correlated(P<0.05) with hyperbilirubinemic neonates in the control group. Planktothricoides and Veillonella were positively correlated (P<0.05) with hyperbilirubinemic neonates in the control group,  and unclassified Enterobacteriaceae were negatively correlated (P<0.05) with hyperbilirubinemic neonates in the cefodizime group. The comparison of the distribution of intestinal microbiota at the genus level showed a significant difference in the abundance of 46 bacteria between the hyperbilirubinemia group and the control group(P<0.05). Metabolic changes in hyperbilirubinemic neonates in the antibiotic use group were mainly in the pentose phosphate pathway (P<0.01),  and alanine, aspartate,  and glutamate metabolism(P<0.01),  as compared to control neonates. Enterococcus and Carnobacterium were positively associated with the differential metabolite succinate (rs=0.692 3, 0.521 7, P<0.01).Conclusion The mode of delivery and the use of antibiotics can affect the neonatal intestinal microbiota and its metabolites. There is a correlation between intestinal microecology and the development of neonatal hyperbilirubinemia.

Key words:

Hyperbilirubinemia, Intestinal microbiota, Sequencing and metabolism, Antibiotics