Abstract

Background: Breast milk jaundice (BMJ) is the first cause of neonatal jaundice; however, its underlying mechanism is yet to be deciphered. We conducted a study to investigate intestinal flora in neonates with BMJ and used metabolomics to decipher the possible mechanisms by which intestinal flora induces jaundice.Methods: Microbiota collected from the feces of BMJ patients and jaundice-free breastfeeding newborns was used for 16S rRNA sequencing. In addition, differences in fecal metabolites were analyzed using gas chromatography mass spectrometry (GC/MS). The relationship between intestinal microbiota and the differences in fecal metabolites was then analyzed.Results: There was no significant difference in the richness and diversity of intestinal flora between BMJ and the control group; however, there were differences in the structure. At the phylum level, the relative abundance of Firmicutes was higher in the control group compared to the BMJ group, whereas Proteobacteria was higher in the infants with BMJ. Additionally, at the genus level, the relative abundance of Haemophilus was higher in the control group, whereas the relative abundances of Escherichia, Morganella, and Rothia were lower. More remarkably, the major differences in metabolites between the two groups were glyceric acid, succinic acid, and phenylalanine. Additionally, the abundance of Escherichia was positively correlated with succinic acid and cadaverine levels.Conclusions: The intestinal flora colonization status in BMJ patients is immature. This study reports for the first time that the study of intestinal flora, especially Escherichia, plays an important role in BMJ, and found that it may be associated with the regulation of succinic acid metabolic pathways.

Highlights

  • Neonatal jaundice is one of the most common manifestations observed during the neonatal period

  • The absence of gut microflora required for the conversion of bilirubin to stercobilin, such as Clostridium ramosum, Clostridium perfringens, Clostridium difficile, and Bacteroides fragilis, results in higher bilirubin levels in the intestinal tract, which leads to elevated enterohepatic circulation [5]

  • Structure, and diversity of intestinal flora in neonates with Breast milk jaundice (BMJ) and subsequently used metabolomics to understand the possible mechanisms by which intestinal flora induces jaundice

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Summary

Introduction

Neonatal jaundice is one of the most common manifestations observed during the neonatal period. Breast milk jaundice (BMJ) is the first cause of neonatal jaundice, which is characterized by unconjugated hyperbilirubinemia associated with breastfeeding [1]. The exact mechanism for BMJ is unknown but may involve decreased caloric intake, which is called breast feeding jaundice, inhibition of hepatic bilirubin excretion, and increased intestinal bilirubin reabsorption. The absence of gut microflora required for the conversion of bilirubin to stercobilin, such as Clostridium ramosum, Clostridium perfringens, Clostridium difficile, and Bacteroides fragilis, results in higher bilirubin levels in the intestinal tract, which leads to elevated enterohepatic circulation [5]. Breast milk jaundice (BMJ) is the first cause of neonatal jaundice; its underlying mechanism is yet to be deciphered. We conducted a study to investigate intestinal flora in neonates with BMJ and used metabolomics to decipher the possible mechanisms by which intestinal flora induces jaundice

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