Probiotics to Protect the Intestines and Brain

Necrotizing enterocolitis (NEC) is a debilitating and deadly condition that affects infants who were born preterm. In NEC cases, intestinal tissues become inflamed, and in severe cases there is ischemia and death of the involved intestines. 

“Even after decades of research, little has changed in terms of prognosis for infants who develop NEC,” says Gail Besner, MD, pediatric surgeon and principal investigator in the Center for Perinatal Research at Nationwide Children’s. 

Dr. Besner and her collaborators Michael Bailey, PhD, and Steven Goodman, PhD, both principal investigators in the Center for Microbial Pathogenesis at Nationwide Children’s, have been working on a novel solution to prevent NEC. They have developed a novel probiotic system that harnesses the durability of biofilms to improve the administration of probiotics to patients. It has been licensed to Scioto Biosciences.

Their latest study describes the use of a biofilm formation of Limosilactobacillus reuteri (Lr) to prevent NEC in a piglet model.

“Our previous studies have shown that the biofilm probiotic works in mouse and rat models,” says Dr. Besner. “But there are many examples where researchers find something that works in rodents, but it fails to translate to humans. We wanted to show that this approach to preventing NEC would work in an animal model that was more similar to humans.”

Dr. Besner and her team therefore adapted the very challenging piglet model of NEC into her laboratory for this study. Notably, preterm piglets and preterm humans are very similar in terms of size and intestinal anatomy. Care that would normally be given to a preterm infant, including medications and fluids, nasogastric (NG) tube feedings, and round-the-clock monitoring, are all included in the model.

Findings demonstrate the superiority of Lr in its biofilm state compared to planktonic (free-living) Lr in preventing the morbidity and mortality associated with NEC. Importantly, Lr in its biofilm state not only protects the intestines from NEC, but protects the brain as well, a finding of great potential importance for survivors of NEC.

“The piglet is an excellent model to help prepare for studies in neonates. The data from this study help us understand the safety and efficacy profile of this novel formulation. This will be helpful as we work with the FDA to plan for future human studies,” says Joe Trebley, PhD.

A similar probiotic formulation developed by the team, SB-121, has been tested in a clinical trial in adults with autism spectrum disorder (ASD). The association between the brain and the gut symptoms in autism has been well-established in the literature, with more than half of people with autism also experiencing abdominal problems. The study, which primarily evaluated the safety of SB-121, also found that some participants showed treatment-driven improvements in their ASD test outcomes. 

“Taken together, the current piglet study, the previous rodent studies, and the recent SB-121 clinical trial provide a solid foundation for pursuing a clinical trial in neonates at risk of developing NEC,” says Dr. Besner. 

Sources:

Samantha J. Wala, Nitin Sajankila, Mecklin V. Ragan, Audrey F. Duff, Joseph Wickham, Samuel G. Volpe, Yijie Wang, Miriam Conces, Zachary Dumbauld, Nanditha Purayil, Siddharth Narayanan, Adrian Rajab, Belgacem Mihi, Michael T. Bailey, Steven D. Goodman, Gail E. Besner. Superior performance of biofilm versus planktonic Limosilactobacillus reuteri in protection of the intestines and brain in a piglet model of necrotizing enterocolitis. Scientific Reports, 2023; 13 (1) DOI: 10.1038/s41598-023-44676-5

Nationwide Children’s Hospital. “Probiotics delivered in biofilm state protect the intestines and brain in NEC model.” ScienceDaily. ScienceDaily, 23 October 2023. <www.sciencedaily.com/releases/2023/10/231023124356.htm>.

Materials provided by Nationwide Children’s Hospital. Note: Content may be edited for style and length.

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