Probiotic Treatment Promotes Neurodevelopment After Experimental Necrotizing Enterocolitis

Gail Besner, MD

Gail Besner, MD, is chief of Pediatric Surgery at Nationwide Children's Hospital.

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Researchers at Nationwide Children’s Hospital have demonstrated that when given in a biofilm state, probiotic Lactobacillus reuteri prevents the neurodevelopmental sequelae of experimental necrotizing enterocolitis (NEC).

The findings, published in Brain, Behavior, & Immunity – Health, have significant implications for bench-to-bedside translation of this microsphere-based probiotic delivery system that promotes biofilm development and potentially reduces the harmful effects of clinical NEC in neonates.

“In the last seven decades, despite an incredible amount of progress in treating most pediatric diseases, relatively little progress has been made in the ability to prevent babies with NEC from dying or from developing severe consequences of the disease in those that survive,” says Gail Besner, MD, chief of Pediatric Surgery and a principal investigator in the Center for Perinatal Research at Nationwide Children’s.

The study has emerged from a collaboration among the laboratories of Dr. Besner, Steven Goodman, PhD, and Michael Bailey, PhD. The multidisciplinary team previously demonstrated that a single dose of L. reuteri delivered in its biofilm state protects the intestines from injury in an animal model of NEC, significantly reducing NEC incidence and severity.


“In all clinical trials of probiotics to protect babies from NEC to date, the probiotics have been administered in their free-living state. However, bacteria thrive and are much more effective in a biofilm state,” adds Dr. Besner.

Approximately 45% of infants who survive NEC will have neurodevelopmental deficits as they age. The study aimed to determine whether a single dose of the probiotic therapy could protect the brain after experimentally-induced NEC in a rodent model. The investigators first confirmed that rat pups exposed to NEC took significantly longer to reach developmental milestones, such as eye and ear opening, body coordination and forelimb grasp strength, and experienced negative effects on cognitive behaviors, such as those required for learning and memory, compared with control pups.

When NEC-exposed rat pups were administered the probiotic treatment, the negative effects on cognitive behavior were prevented, anxiety-like behaviors were reduced, and memory was improved.

The team found that the behavioral effects of NEC were associated with increased numbers of activated microglia, decreased levels of a protein component of myelin, and decreased neurotrophic gene expression, all of which were prevented by the probiotic treatment.

“It is very powerful that a single dose of this probiotic treatment can reduce the incidence of disease and protect the brains of animals after they have experienced NEC,” says Dr. Besner.

Wang Y, Jaggers RM, Mar P, Galley JD, Shaffer T, Rajab A, Deshpande S, Mashburn-Warren L, Buzzo JR, Goodman SD, Bailey MT, Besner GE. Lactobacillus reuteri in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in rats. Brain Behav Immun Health. 2021 Jul;14:100256.
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. J Pediatr Surg. 2016 Jun;51(6):936-41. Doi: 10.1016/j.jpedsurg.2016.02.062. Epub 2016 Mar 2. PMID: 27032609.
Olson JK, Navarro JB, Allen JM, McCulloh CJ, Mashburn-Warren L, Wang Y, Varaljay VA, Bailey MT, Goodman SD, Besner GE. An enhanced Lactobacillus reuteri biofilm formulation that increases protection against experimental necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol. 2018 Sep 1;315(3):G408-G419.