Can gut bacteria and metabolites help the earlier prediction of necrotizing enterocolitis in newborns?

Identify early and intervene as soon as possible. This is the key to managing neonatal necrotizing enterocolitis (NEC), which affects between 5% and 12% of premature babies. However, due to a lack of sufficiently sensitive biomarkers in newborns, this remains wishful thinking. Nonetheless, previous studies have shown the appearance of a gut dysbiosis in the 7 days to 72 hours preceding NEC. Can the microbiota and its metabolites – particularly short-chain fatty acids (SCFAs) involved in maintaining the integrity of the intestinal epithelium – predict NEC?

34 preterm infants with digestive disorders

To explore the predictive value of the gut microbiota and SCFAs, a prospective study was conducted in 34 preterm infants (gestational age less than 34 weeks) suffering from gut disorders (bloating, vomiting, or bloody stools). 17 of the infants were suspected of having NEC and 17 were matched controls without NEC whose stools were collected on the enrollment day. Of the 17 infants suspected of having NEC, the diagnosis was confirmed in only 12 (sidenote: Gut perforation The remaining 5 children showed gut perforation on the day of enrollment in the study. ) (a subgroup of the original matched sample), whose stool was collected seven days later on average.

Gut dysbiosis precedes NEC

Contrary to the results of previous studies, the researchers did not systematically observe a loss of gut diversity prior to the disease: some indices of bacterial richness (Ace and Chao1) showed a significant difference, while others (Simpson and Shannon) did not. According to the authors, the digestive disorders present in all children in the study (including the controls) may explain this discrepancy with the data from the literature.

Conversely, seven days before the onset of NEC, a change in the composition of the flora was noted: the bacterial species Streptococcus salivarius and Rothia mucilaginosa increased, while Bifidobacterium subsp. lactis decreased. Variations at phylum level (increase in Proteobacteria, decrease in Firmicutes, Actinobacteriota, and Bacteroidota) were also explored, but the differences were not deemed significant.

Three SCFAs as metabolic markers

The researchers also looked at bacterial metabolites, specifically acetate, propionate, and butyrate, which represent 90%-95% of total SCFAs in the human gut. The study showed that these three SCFAs decreased significantly seven days before the onset of NEC, probably due to the decrease in Firmicutes and Bacteroidota. These metabolites proved to be much better predictive biomarkers for NEC than the bacterial biomarkers. More specific and sensitive (AUC of 68%-73%, depending on the SCFA), in the future they may have a clinical application.