IP Library › Granted Patent US 12,453,747
Granted Patent B2
US 12,453,747 · App. 16/961,910 · Granted Oct 28, 2025

Prebiotic formulations for prevention of sepsis and necroenterocolitis induced neurodevelopmental deficiencies

Inventors: Gail E. Besner (Columbus, OH); Michael Bailey (Columbus, OH); Steven Goodman (Columbus, OH)
Assignee: Research Institute at Nationwide Children's Hospital
A61K35/747A61K9/1647A61K35/742A61K35/744A61K35/745A61K47/42A61P25/28
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Quick Facts
Patent No.
US 12,453,747
App. No.
16/961,910
Granted
Oct 28, 2025
Kind
B2
Abstract

Provided herein are methods and probiotic compositions for treating or preventing a disease or neurodevelopmental deficiency in a subject in need thereof using the compositions. Aspects and embodiments of this technology combine the health benefits of probiotic bacteria with prebiotic substances to help stimulate the exclusive growth of the probiotic species and, in one aspect, provide the bacteria in the form of a biofilm on a biocompatible microsphere.

Claims (27)

1. A method of treating necrotizing enterocolitis (NEC)-induced neurodevelopmental deficiencies in a subject suffering from or has suffered from necrotizing enterocolitis (NEC), comprising administering to the subject an effective amount of a composition comprising a microsphere comprising a biofilm-generating probiotic L. reuteri bacterium and a prebiotic, wherein the bacterium forms a biofilm partially or completely coating the surface of the microsphere, and wherein the prebiotic comprises a nutritional supplementation for the probiotic L. reuteri bacterium.

2. The method of claim 1 , wherein administration of the composition prevents, decreases or delays microglial activation in the subject.

3. The method of claim 2 , wherein administration of the composition further decreases cell body thickness of microglia in the subject relative to a control subject.

4. The method of claim 1 , wherein administration of the composition further thins the dendritic processes of microglia in the subject relative to a control subject.

5. The method of claim 1 , wherein administration of the composition further increases expression of brain-derived neurotrophic factor (BDNF) in the subject.

6. The method of claim 5 , wherein the increased expression of BDNF is in the hippocampus of the subject.

7. The method of claim 1 , wherein administration of the composition further increases expression of Grin2A in the subject.

8. The method of claim 7 , wherein the increased expression of Grin2A is in the prefrontal cortex of the subject.

9. The method of claim 1 , wherein the microsphere comprises the complete biofilm coating on an external surface of the microsphere.

10. The method of claim 1 , wherein the bacterium and the prebiotic diffuse from an interior of the microsphere to a surface of the microsphere.

11. The method of claim 1 , wherein the composition further comprises one or more of: a prebiofilmic that supports biofilm formation and durability, a therapeutic drug or agent, a chemical reductant, a molecule that promotes adsorption, and a molecule that supports absorption.

12. The method of claim 11 , wherein the prebiofilmic is a DNA binding polypeptide or protein and/or a DNABII polypeptide or protein or an equivalent of each thereof.

13. The method of claim 1 , wherein the probiotic bacterium further provides one or more of supporting anti-bacterial immunity, correcting dysbiosis, enhancing or supporting the gastrointestinal barrier, supporting or enhancing gastrointestinal motility, localized release of antibiotic compositions, antagonizing disease-related bacterial infections, or prevents deficiencies in one or more of body strength, coordination, righting mechanism, auditory reflex tests, curiosity, learning ability, cognitive ability, social interaction, working memory, short term memory, long-term memory, visuo-spatial reasoning, cognition, object recognition, serotonin, prevention of pathogen colonization, and limiting excessive inflammatory responses by down-regulating cytokine and chemokine production.

14. The method of claim 1 , wherein the microsphere comprises a solid core or a hollow core and the prebiotic is encapsulated within the hollow core or comprises the core of the microsphere.

15. The method of claim 1 , wherein the microsphere comprises dextranomer and the prebiotic comprises maltose, glycerol, or histidine.

16. The method of claim 1 , wherein the composition was prepared by admixing the microsphere with the biofilm-generating probiotic bacterium and the prebiotic and optionally, in a culture comprising a biofilm.

17. The method of claim 1 , wherein release of the prebiotic is regulated by varying microsphere size or by altering the viscosity of the prebiotic or both.

18. The method of claim 1 , wherein the subject is suffering from, or has suffered from Bell's stage 2 or 3 NEC, or where the NEC has been treated with surgery.

19. A method of attenuating or delaying necrotizing enterocolitis (NEC)-induced neurodevelopmental deficiencies in a subject suffering from or has suffered from Bell's stage 2 or 3 NEC, or where the NEC has been treated with surgery, comprising administering to the subject an effective amount of a composition comprising a microsphere comprising a biofilm-generating probiotic L. reuteri bacterium and a prebiotic, wherein the bacterium forms a biofilm partially or completely coating the surface of the microsphere, and wherein the prebiotic comprises a nutritional supplementation for the probiotic L. reuteri bacterium.

20. The method of claim 1 , wherein the method further provides an improvement in a deficiency in one or more of body strength, coordination, righting mechanism, auditory reflex tests, curiosity, learning ability, cognitive ability, social interaction, working memory, short term memory, long-term memory, visuo-spatial reasoning, cognition, or object recognition.

21. The method of claim 19 , wherein the method further provides an improvement in a deficiency in one or more of body strength, coordination, righting mechanism, auditory reflex tests, curiosity, learning ability, cognitive ability, social interaction, working memory, short term memory, long-term memory, visuo-spatial reasoning, cognition, or object recognition.

22. The method of claim 1 , wherein the subject is not suffering from anxiety or depression.

23. The method of claim 19 , wherein the subject is not suffering from anxiety or depression.

24. The method of claim 1 , wherein the microsphere comprises dextranomer and the prebiotic comprises maltose.

25. The method of claim 19 , wherein the microsphere comprises dextranomer and the prebiotic comprises maltose.

26. The method of claim 24 , wherein the microsphere comprises the complete biofilm coating on an external surface of the microsphere.

27. The method of claim 25 , wherein the microsphere comprises the complete biofilm coating on an external surface of the microsphere.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 22, 2021
From: BESNER, GAIL E.; BAILEY, MICHAEL; GOODMAN, STEVEN
To: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Reel/Frame 058187/0449 →
CONFIRMATORY LICENSE Recorded Oct 1, 2020
From: CHILDREN'S HOSPITAL (COLUMBUS)
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 053966/0314 →
Continuity (2)
Provisional Application 62856704 · Jun 3, 2019
Related Publication 20210401904A1 · Dec 30, 2021
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