Preterm infants are at a high risk of growth failure that may affect their long-term health outcomes. Different factors have been involved in the etiology of postnatal growth failure in preterm infants, but despite research efforts regarding clinical management, growth failure rates continue to increase.

Although differences in gut microbiota composition have been found in preterm infants compared with full-term infants, the extent to which postnatal growth failure affects gut microbiota and metabolic development in preterm infants remains elusive.

A new prospective cohort study, led by Dr. Patricia L. Ashley from the Department of Pediatrics at Duke University (USA), has found that growth failure in extremely preterm infants is associated with altered gut microbiota composition and metabolome during the first 9 weeks of life.

Compared with preterm infants with appropriate growth (n=22), those with growth failure (n=36) showed disrupted maturation of the gut microbiota involving low diversity, a higher abundance of Staphylococcaceae, followed by persistent dominance of Enterobacteriaceae and a lack of strictly anaerobic bacteria.

Through a machine learning-based approach generated from fecal samples that computes a microbiota maturity index and a microbiota-for-age score, the authors found that preterm infants with growth failure showed a disrupted maturation of their gut microbiota compared with infants showing appropriate growth. These results could not be explained by the influence of birth gestational age and complications secondary to extreme prematurity, including late-onset sepsis, necrotizing enterocolitis, and spontaneous intestinal perforation.

Despite the fact that both groups had a similar caloric intake, preterm infants with growth failure also showed an altered serum metabolomic profile characterized by increased lipolysis and fatty acid oxidation, resembling fasting.

Specifically, the researchers reported an increase in short- and medium-chain acylcarnitines in the growth failure group, whereas infants with appropriate growth exhibited higher long-chain acylcarnitines. Furthermore, infants with growth failure had higher levels of fatty acid caused by oxidation, together with an increase in glycerol, which reflects increased lipolysis.

Similarly, Dr. Jeffrey Gordon and colleagues previously reported that transferring the microbiome of malnourished children into germ-free mice resulted in an enrichment of the metabolic pathways related to enhanced fatty acid mobilization and oxidation.

Along with the authors’ observation of the gut microbiota’s disrupted maturation in infants with growth failure, they also showed that growth failure was associated with delayed metabolic maturation.

Finally, the gut microbiota was grouped into different clusters depending on which metabolism pathways were enriched, the different groups (infants with growth failure vs. infants with appropriate growth) and time points. Consequently, some correlations were found between Veillonella and Peptostreptococcaceae, along with individual amino acids and acylcarnitines.

Altogether, these findings show an altered maturation of the gut microbiota composition and metabolome in preterm infants with growth failure. This underlines that the gut microbiota of these infants can have an impact on the host metabolome, making the gut microbiome and metabolome potential future targets for using nutrition to manage growth failure.



Younge NE, Newgard CB, Cotten CM, et al. Disrupted maturation of the microbiota and metabolome among extremely preterm infants with postnatal growth failure. Sci Rep. 2019; 9(1):8167. doi: 10.1038/s41598-019-44547-y.