5 February 2021

Researchers want to reduce mortality among very preterm infants

Intestinal virus

Very preterm infants, who weigh less than 1,500 grams at birth (typically born before week 32 of gestation), have a greatly increased risk of the serious intestinal disease necrotizing enterocolitis (NEC). Researchers from the University of Copenhagen and Rigshospitalet in Denmark want to prevent this through a new research project, PrePhage

Virus cocktail is centrifuged in the fecal laboratory at KU FOOD
Virus cocktail is centrifuged in the fecal laboratory at KU FOOD

Approximately 1% of all infants are born very prematurely; i.e. before the end of the 32nd week of pregnancy, which is associated with a high risk of disease. Due to the children’s immature gastrointestinal tract, extensive use of antibiotics, eating problems, etc., the development of the intestine and the intestinal microbiome typically lags behind and the children have an increased risk of developing necrotizing enterocolitis (NEC).  The disease occurs in 6-7% of very preterm infants and the mortality rate is about 30%.

“NEC is a terrible disease that kills many infants every year. And those who survive the disease often end up having parts of the intestine removed, resulting in lifelong complications. In pig trials, we have shown that we can reduce the incidence of NEC enormously by transferring so-called faecal virome from pigs born at term to pigs born prematurely. The aim of the project is to pave the way for a similar treatment to be used in humans,” explains Professor MSO Dennis Sandris Nielsen from the Department of Food Science at the University of Copenhagen (UCPH FOOD). 

Research on very preterm pigs conducted in collaboration between Professor Thomas Thymann, postdoc Anders Brunse and Dennis Sandris Nielsen has already shown that faecal transplantation of intestinal bacteria from healthy, suckling piglets significantly reduces the risk of NEC, but the result is donor dependent and involves a risk of transmitting intestinal bacteria to the blood and organs. As a potentially safer alternative, the researchers also tested a faecal filtrate where the bacteria were sorted out, so what remained was mainly viruses, the majority of which were so-called bacteriophages. This treatment is called FVT – “faecal virome transfer”. Bacteriophages are viruses that make targeted attacks on bacteria in the piglets’ gastrointestinal tract and the hypothesis was therefore that the piglets’ risk of NEC would decrease.

Treatment with virus had fewer side effects

It turned out that the FVT treatment prevented NEC best if the piglets received the transplant orally. With the oral FVT treatment, none of the pigs developed NEC, while more than 50% of the pigs in the control group developed NEC. Faecal virome transfer thus proved to be a potentially promising preventative treatment for preterm infants, but a long series of trials are still needed before the treatment can be tested on humans.

Therefore, the aim of the research project PrePhage is to develop a bacteriophage-based preventive treatment that improves intestinal maturation and prevents the development of NEC in very preterm infants. In order to achieve this goal, the researchers will initially investigate the safety and effectiveness of the treatment in a piglet-based model of very preterm infants. They will also develop a comprehensive donor screening program among healthy infants born at term and eventually perform a Phase 1 clinical trial at Rigshospitalet in Copenhagen, Denmark.

If successful, PrePhage will lead to the development of a new preventive tool to minimise the risk of NEC in the very vulnerable group of very preterm infants.