Intestinal microbiome in very-preterm infants at one month of age and association with neurodevelopmental outcome.

The gut microbiome of very preterm infants at one month of age is primarily driven by either Escherichia or Staphylococcus.

• Analysis was performed on fecal samples from 73 very preterm French infants collected in 2011 at one month of age.
• Multi-omics profiling included fecal microbiome (16S rRNA gene sequencing), metabolome (LC-MS), and host transcriptome (mRNA sequencing).
• Infants were grouped according to neurodevelopmental outcomes assessed at two years of age using the Ages & Stages questionnaire.
• Analyses were performed between 2022 and 2023.

Escherichia and Staphylococcus proportions were identified as the best indicators of physiological maturity and immaturity, respectively.

• Escherichia was associated with physiological maturity in very preterm infants at one month of age.
• Staphylococcus was associated with physiological immaturity.
• These two genera were differentially associated with host immune markers, notably CAMP (cathelicidin antimicrobial peptide).
• The two genera were also differentially associated with metabolomic pathways, notably the energy pathway involving nicotinamide adenine dinucleotides (NAD+).

Escherichia dominance at one month of age was associated with better neurodevelopmental outcomes at two years of age.

• Neurodevelopmental outcome was assessed at two years of age using the Ages & Stages questionnaire.
• Escherichia may help the process of intestinal maturation in preterm infants through specific metabolite production.
• The association between Escherichia and better neurodevelopment was identified through integrative multi-omics analysis.
• Staphylococcus dominance was associated with less favorable neurodevelopmental outcomes compared to Escherichia dominance.

The gut microbiome at one month of age was differentially associated with the host immune marker CAMP depending on dominant genus.

• CAMP (cathelicidin antimicrobial peptide) was identified as a host immune marker differentially expressed between Escherichia- and Staphylococcus-dominated infants.
• Host transcriptome characterization was performed using mRNA sequencing of fecal samples.
• This association was identified through integrative multi-omics analysis.

The gut microbiome at one month of age was differentially associated with energy metabolic pathways, particularly involving nicotinamide adenine dinucleotides (NAD+), depending on dominant genus.

• Metabolomic characterization was performed using LC-MS on fecal samples.
• Various nicotinamide adenine dinucleotides (NAD+) were identified as key metabolites differentiating the two microbiome types.
• The energy pathway was notably different between Escherichia- and Staphylococcus-dominated infants.
• These metabolic differences may contribute to the differential neurodevelopmental outcomes observed.

The gut microbiome at one month of age was proposed as a noninvasive biomarker of gut immaturity and metabolic defects in very preterm infants.

• The study population consisted of 73 very preterm French infants.
• Fecal samples were used, making the approach noninvasive.
• The biomarker potential was based on the differential associations between dominant microbiome genera and host physiological, metabolic, and neurodevelopmental outcomes.
• Very preterm birth is described as the leading cause of death in children under five years of age worldwide.