One Dose Probiotic Biofilm Protects Against NEC

A single dose of a probiotic biofilm grown on microspheres prevented or significantly reduced the severity of necrotizing enterocolitis (NEC) in animal models of the disease, researchers show.

This delivery method not only appears to protect against NEC but the fact that it is effective after administration of only a single dose may avoid the bacteremia and other morbidities resulting from the currently required administration of repeated, high doses of probiotics, according to an article published in June in the Journal of Pediatric Surgery.

Nearly 10 percent of infants born weighing less than 3.3 pounds develop NEC. The disease kills 20 to 30 percent of affected babies – a figure that’s changed little in 50 years.

“In general, physicians think of biofilms as their enemy, because biofilms protect pathogenic bacteria from antibiotic therapy,” says Gail E. Besner, MD, chief of Pediatric Surgery and a principal investigator in the Center for Perinatal Research in The Research Institute at Nationwide Children’s.

Dr. Besner teamed with Steven Goodman, PhD, principal investigator in the Center for Microbial Pathogenesis at Nationwide Children’s, who suggested they investigate whether a probiotic administered as a biofilm and introduced into the stomach could colonize long enough to do its job better, and to determine if that’s enough to make a difference.

“If you could give a single dose of probiotic bacteria at a level that protects before NEC gets started, that’s the holy grail,” Dr. Goodman says.

The researchers chose their materials carefully.

First, they selected the probiotic Lactobacillus reuteri because its anti-inflammatory and antimicrobial activities may counter two harmful NEC activities. Then, they chose a surface for the biofilm to form: commercially made Sephadex microspheres. The spheres are made of material similar to the glycans L. reuteri normally synthesizes and binds to itself but is relatively inert to other bacteria, Dr. Goodman says.

In testing, 69 percent of untreated subjects developed NEC compared to only 14 percent of those treated with L. reuteri grown on the microspheres. Animals treated with this novel probiotic delivery system had substantially reduced intestinal permeability, indicating improved intestinal function.

The researchers are now closely characterizing the biofilm, microspheres and their interactions as well as experimenting with different cargos, to boost protection against NEC. They hope to begin clinical trials using an optimized version within three years.

“NEC attacks the youngest, smallest, and most vulnerable premature babies that we care for in the hospital,” Dr. Besner says. “It may be that a single dose of something that’s very safe delivered in this manner will give them a chance to live.”

Reference:

Olson JK, Rager TM, Navarro JB, Mashburn-Warren L, Goodman SD, Besner GE. Harvesting the benefits of biofilms: a novel probiotic delivery system for the prevention of necrotizing enterocolitis. Journal of Pediatric Surgery. 2016 Jun;51(6):936-941.