Why do some extremely premature babies fail to grow while others prosper, despite similar diets? New research suggests these metabolic differences are underpinned by specific gut microbiome alterations that leave some preterm infants in a physiological state similar to fasting.

The first few months in a prematurely born baby's life are profoundly important with postnatal growth critical to a preterm baby's healthy development. Modern medical science and nutritional practices have improved infant growth in these important weeks, but there are still many preterm babies that inexplicably do not progress at the same rate as others.

Some preterm babies seem to be unable to metabolize nutrients as efficiently as others, and this observation has led some researchers to hypothesize gut microbiome differences may potentially play a major role. Prior observational studies have confirmed a strong association between preterm infant growth and gut microbiome alterations, and this new research further homes in on that association by examining more specifically how these gut bacteria disruptions could be affecting a baby's ability to metabolize nutrients.

The new research followed 58 preterm infants, all with a median gestational age of 26 weeks. At the 40-week point, 60 percent of the infants were classified as having severe postnatal growth failure, meaning their weight was less than the third percentile on sex-specific general growth charts. Comparing microbiome and metabolic signatures of the infants with growth failure to the preterm infants with appropriate growth, the researchers discovered significant associations they believe could help improve preterm baby development in the future.

"Our analyses of the relationship between the microbiome of infants with growth failure and the byproducts of their metabolism suggest that the unique composition of bacterial communities living in their gut might play a role in this metabolic state with similarities to fasting," explains senior author on the study, Patrick Seed.

Alongside notable gut microbiome alternations in the infants with growth failure, the researchers identified compelling metabolic differences suggesting the babies were in a persistent physiological state similar to that of fasting. Deficiencies in glucose metabolism and elevations in multiple fatty acids resembled metabolic profiles seen in malnourished children. This was despite that fact these preterm babies were fed the same caloric diet as those preterm babies ultimately reaching appropriate growth levels by 40 weeks.

Even after accounting for other clinical preterm complications such as illness, inflammation or intestinal perforation, these significant metabolic and microbiome differences remained. This raises the reasonable hypothesis that disruptions in a baby's microbiome development can result in metabolic impairments that affect critical growth in the weeks and months following preterm birth.

"Currently we lack the means to identify infants at highest risk of growth failure," says Seed on the value of this new research. "The microbiome might give us the insights we need to guide individualized interventions and measure response to therapy."

The next step in the research is to verify these metabolic and microbiome differences in a larger cohort of babies. This will initially allow for accurate biomarkers that can help identify those preterm babies at greatest risk of subsequent growth failure. After that the investigations will examine ways to assist microbiome and metabolic maturation in these vital stages of infant development.

The new research was published in the journal Scientific Reports.