Neonatal intensive care unit (NICU) exposures exert a sustained influence on the progression of gut microbiota and metabolome in the first year of life

Polly Soo Xi Yap,Yao Mun Choo,Cindy Shuan Ju Teh,Ivan Kok Seng Yap,Nai Ming Lai,Chun Wie Chong,Azanna Ahmad Kamar

doi:10.1038/s41598-020-80278-1

Abstract

Emerging evidence has shown a link between the perturbations and development of the gut microbiota in infants with their immediate and long-term health. To better understand the assembly of the gut microbiota in preterm infants, faecal samples were longitudinally collected from the preterm (n = 19) and term (n = 20) infants from birth until month 12. 16S rRNA gene sequencing (n = 141) and metabolomics profiling (n = 141) using nuclear magnetic resonance spectroscopy identified significant differences between groups in various time points. A panel of amino acid metabolites and central metabolism intermediates significantly correlated with the relative abundances of 8 species of bacteria were identified in the preterm group. In contrast, faecal metabolites of term infants had significantly higher levels of metabolites which are commonly found in milk such as fucose and β-hydroxybutyrate. We demonstrated that the early-life factors such as gestational age, birth weight and NICU exposures, exerted a sustained effect to the dynamics of gut microbial composition and metabolism of the neonates up to one year of age. Thus, our findings suggest that intervention at this early time could provide ‘metabolic rescue’ to preterm infants from aberrant initial gut microbial colonisation and succession.

Highlights

Preterm birth is one of the major determinants of neonatal mortality and morbidity
The complications of preterm birth and morbidity arise from immature organ systems that are incapable of supporting life in the extra-uterine environment
There is a lack of information regarding the contribution of gut microbial composition to host metabolism, and the interplay between both in the growth of preterm infants

Summary

Introduction

Preterm birth is one of the major determinants of neonatal mortality and morbidity. Prematurity is wellrecognised to carry long term consequences on health well into the infants’ adult life. Limited studies have advanced interpretations on the impact of degree of prematurity at birth and postnatal environment (for e.g. treatments received in NICU) in terms of longitudinal associated patterns, especially gut microbiota maturation after weaning, despite increasing evidence of the population dynamics of the human gut microbiome[17]. Despite the significant health burden of preterm birth, the consequences of impaired maturation of gut microbiota to the development of preterm infants to adult life remained poorly studied, especially in South East Asia. We compared the variations in the faecal microbial composition and metabolome between preterm and term infants at varying time points from birth to month 12. The pattern of gut bacterial assemblages and metabolic profiles were modelled using selected clinical characteristics while the relationship of microbial taxa and metabolites that differed significantly across different time points was assessed through sparse partial least squares correlation analysis

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Conclusion