# A Pilot Multi-Omics Approach Unveils Strong Immune Activation in the First Ten Days of Life in Extremely Preterm Infants

## TL;DR

This study uses a multi-omics approach to show that extremely preterm infants experience significant immune and metabolic changes in their first ten days of life.

## Contribution

The study demonstrates the feasibility of using multi-omics to simultaneously analyze immune and metabolic changes in preterm infants.

## Key findings

- 1185 genes were found to be differentially expressed, linked to immune function and development pathways.
- Five metabolites showed significant differential abundance, associated with altered sugar and fat metabolism in preterm infants.
- Metallothionein pathways were downregulated, offering insights into metabolic changes during early life.

## Abstract

Background: Very preterm infants (VPIs) are born with an undeveloped immune system and are more susceptible to infection. Acquired immune responses must develop in a complex nutritional and metabolic environment as these babies transition from parenteral to enteral nutrition. We explored the feasibility of a multi-omics approach to investigate the changes in metabolic and molecular profiles between day 3 and day 10 of life. Methods: Blood and plasma samples were collected at day 3 and day 10 of life from eight infants born <29 weeks’ gestation and used to perform microarray transcriptomics and 1H NMR metabolomics. All data were analysed using univariate statistics and mapped to biological pathways and molecular functions using an assortment of databases. Results: We found 1185 genes differentially expressed. The expression patterns found mapped to different immune function, maturation, and development pathways as well as providing mechanistic insights into metabolic changes, notably the downregulation of the metallothionein pathways. We found five metabolites that presented significant differential abundance. These linked to sugar and fat metabolic pathways, known to be altered in the preterm infants. Conclusions: We show that a multi-omics approach is feasible in VPIs and can identify simultaneous changes in the complex metabolic processes and immune adaptation that occur in the first ten days of life.