Viral signature may signal deadly gut disease in premature babies

New research highlights how microbial signatures could be used to prevent necrotizing enterocolitis, leading to faster diagnosis.
Table of Contents

What is already known on this topic
Necrotizing enterocolitis, or NEC, is a life-threatening inflammation of intestinal tissue that mostly affects premature babies. Studies have pointed at associations with specific bacteria in the gut of preterm babies, but little is known about the role of gut-dwelling viruses in NEC.

What this research adds
Researchers analyzed 138 stool samples collected from 23 preterm infants every week during the first 11 weeks of life. Of these infants, 9 developed NEC and 14 didn’t. Infants who developed NEC showed specific viral and bacterial signatures in their guts. In particular, they had less diverse gut viruses over a 10-day period before developing NEC.

Conclusions
The findings suggest that microbial signatures in the gut of preterm babies can be used as a biomarker of NEC.

Necrotizing enterocolitis, or NEC, is a life-threatening inflammation of intestinal tissue that mostly affects premature babies. Now, researchers have found that some preemies show alterations in their gut viruses shortly before developing NEC.

The findings, published in Nature Microbiology, suggest that microbial signatures in the gut of preterm babies can be used as a biomarker of NEC.

In babies are born after fewer than 32 weeks of gestation, the incidence of NEC ranges from 2-7% in high-income countries, with 22 to 38% of infants dying from the disease. The causes of NEC are unclear, but risk factors — in addition to preterm birth — may include prolonged use of antibiotics. Previous research also pointed at associations with specific bacteria in the gut of premature babies.

“For many years now, there’s been some inkling that the microbiome is implicated in this rapidly developing disease,” says study senior author Efrem Lim at Arizona State University. “Studies have shown that changes in the microbiome of the gut in these preterm infants seem to predict the progression to NEC disease.” 

However, little is known about the role of gut-dwelling viruses in NEC, so Lim, Lori Holtz at Washington University School of Medicine and their colleagues analyzed stool samples from preterm infants who went onto developing NEC or who didn’t.

Viral signature

The team analyzed 138 stool samples collected from 23 preterm infants every week during the first 11 weeks of life. All the infants were in the neonatal intensive care unit at St. Louis

Children’s Hospital. Of these babies, 9 developed NEC and 14 didn’t. 

The guts of babies who didn’t develop NEC were populated by bacteriophages belonging to the Myoviridae, Podoviridae and Siphoviridae families. Gokushovirinae, Herelleviridae and

Tectiviridae phages were found at low abundances in the stools of these infants.

In the guts of preemies who developed NEC, the researchers found the same types of viruses. However, these babies showed specific gut viral signatures shortly before developing NEC. In particular, they had less diverse viruses in their guts over a 10-day period before the onset of the first symptoms of NEC.

Microbial convergence

Further analyses showed that virus-bacteria associations in the guts of infants who developed NEC differed from those who didn’t develop the disease. This convergence may contribute to the development of NEC, the researchers say.

For example, Escherichia coli phages have been shown to worsen colitis in mice, and Staphylococcus aureus and Pseudomonas aeruginosa phages are known to trigger the production of immune molecules involved in inflammation.

“Our results indicate that bacterial and viral perturbations precede the sudden onset of NEC,” the authors say. “These findings suggest that early life virome signatures in preterm infants may be implicated in NEC”. The study also highlights how microbial signatures could be used to prevent disease, leading to faster diagnosis for NEC and other diseases mediated by the microbiota.