Probiotic Biofilm May Help Prevent Deadly Gastrointestinal Infections in Premature Infants

Researchers have developed a new form of a probiotic biofilm to protect premature infants from the rare, life-threatening intestinal infection necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a dangerous gastrointestinal condition, with 90% of cases occurring in infants born premature, though it can occur in full-term and near-term newborns. An estimated 12% of infants born under 3.3 pounds will develop NEC, and while about 30% of all infants with these infections do not survive, those who are 5.5 pounds or more have a lower mortality rate. The exact cause of these infections is unknown, and symptoms of the disease may include bloody stools, abdominal distension, vomiting bile-stained fluid, and gas in the bowel wall. While symptoms typically resolve without surgery, treatment can include discontinuing feedings, intravenous fluids and antibiotics, and the use of an orogastric tube to remove fluid and air from the stomach and intestine. Once an infant is no longer showing signs of the infection, feedings may resume by mouth.

Researchers have found that giving probiotics of the Lactobacillus or Bifidobacterium species to premature infants can help reduce overgrowth of pathogenic bacteria in the gut and prevent NEC and death. In addition, feeding human milk to infants rather than formula has been shown to have a protective effect against the condition. In a new study published in the American Journal of Physiology, a team of researchers from Nationwide Children’s Hospital investigated the use of a new form of Lactobacillus reuteri biofilm in animals to reduce the incidence of NEC.

The biofilms are made by introducing cultures of L. reuteri porous, biocompatible, biodegradable dextranomer microspheres. The probiotics adhere to the microspheres and form a biofilm during an incubation period in which the “good” bacteria develop increased resistance to gastric acidity and increased adherence to the gastrointestinal mucosa compared with free-floating bacteria. The newest iterations of the biofilm microspheres are enhanced with sucrose or maltose as diffusible cargo.

“Using probiotics to treat NEC is not a new idea, but administering free-living probiotics has had variable results in clinical trials,” explained senior author Gail Besner, MD, in a recent statement. “Our idea was to develop a safe, effective delivery mechanism to support a one-dose treatment to prevent NEC. In our animal models of the disease, this is what we appear to have accomplished.”

The researchers found that a single-dose L. reuteri biofilm performed well against experimental NEC, reducing the incidence of the condition, improving animal survival, reducing intestinal mucosal barrier breakdown, and limited intestinal inflammation. In addition, the microspheres including maltose changed the gut microbiome to closer simulate that of breastfed babies.

“The use of these microspheres represents an exciting development in improved probiotic administration. As we continue to learn more about the human microbiome and its relationship to health and disease, probiotic administration may play an increasingly important role in disease prevention and management—not just for the application to NEC,” explained Dr Besner.

The new delivery method, according to the researchers, improves upon the use of free-living probiotics. The team is now working with the US Food and Drug Administration (FDA) to design a clinical trial to test the biofilms in humans.

Feature Picture Source: CDC / Dr. Edwin P. Ewing, Jr. / CDC PHIL. Picture caption: This photograph, which is a closer view of PHIL 856, was captured during a child’s autopsy, and depicts the infant’s intestinal tract, and the gross pathologic changes that were caused by a case of neonatal necrotizing enterocolitis. Note the presence of intestinal necrosis, pneumatosis intestinalis, i.e., air in the intestinal wall, and site of intestinal perforation.