Alterations in the Stool Microbiome in Newborns Undergoing Mild Therapeutic Hypothermia after Hypoxic-Ischemic Encephalopathy

Abstract

<b><i>Background:</i></b> Hypoxic-ischemic encephalopathy (HIE) is associated with brain injury in newborns and may lead to disability or death. Mild therapeutic hypothermia (TH) is an effective neuroprotective intervention and an established standard of care in western countries. The gut microbiome, the genomic and physicochemical contribution of the gut microbiota, serves important functions and is increasingly recognized as a major influencer on development. The impact of HIE and TH on the evolving gut microbiota of the newborn remains to be elucidated. <b><i>Objective:</i></b> The objective of this study was to carry out an exploratory study on the effects of HIE and TH on the gut microbiome in term neonates. <b><i>Methods and Results:</i></b> Stool samples were obtained from 28 newborns with HIE (median age 68 h) undergoing TH on the neonatal unit (HIE TH group), with a follow-on stool sample available for 20 of these babies (median age 151 h). For comparison, a single stool specimen was obtained from 19 healthy newborns on the postnatal ward (median age 34 h). The microbiota composition was determined using established microbial DNA extraction and 16S rRNA gene sequencing methodology. There was no difference in the mode of delivery or the method of feeding the newborns, once established, between the 2 groups. All the infants in the HIE TH group had received antibiotics compared to only one of the controls. A lower α-diversity, quantified by the Shannon diversity index, was noted in the microbiota of the HIE TH group in comparison to the control group. The HIE TH group had a higher mean relative abundance (MRA) of facultative anaerobes and aerobes such as <i>Staphylococcus species</i> and a lower MRA of strict anaerobes, such as members of the <i>Bacteroides</i> genus, compared to the control. Also, there was a significant reduction in the MRA of the genus <i>Bifidobacterium</i> in the HIE TH group. Although the mode of delivery exerts a profound influence on the gut microbiota of the newborn, distance-based redundancy analysis showed that TH may exert an independent influence. This study could not determine the independent contribution of the use of antibiotics or the neonatal intensive care unit environment. <b><i>Conclusion:</i></b> In this study, we demonstrate an alteration in the microbiota composition in newborns undergoing TH for HIE.