Composition and methods for predicting necrotizing enterocolitis in preterm infants

Patent metadata

Field	Value
Publication number	US-12139767-B2
Application number	US-201917056562-A
Country	US
Kind code	B2
Filing date	May 22, 2019
Priority date	May 22, 2018
Publication date	Nov 12, 2024
Grant date	Nov 12, 2024

Abstract

A correlative finding between increased Clostridiales and/or Bifidobacteriales bacterial abundance in the gut and intestinal barrier maturation of preterm neonates at-risk for development of necrotizing enterocolitis (NEC) is disclosed. These findings form the basis for the methods of identifying preterm infants at risk for developing necrotizing enterocolitis (NEC), the methods of treating such infants, as well as the methods of characterizing intestinal permeability in preterm infants disclosed herein.

First claim

What is claimed is:

1. A method of treating or preventing high intestinal permeability in a subject comprising:
(a) determining the amount of Clostridiales and/or Bifidobacteriales bacteria in a sample obtained from a subject, and administering a therapeutically effective amount of a treatment or preventive agent for high intestinal permeability (IP) to the subject when the amount of Clostridiales and/or Bifidobacteriales bacteria in the sample is about 5% or less by relative abundance of the total amount of bacteria; or
(b) determining the amount of Clostridiales and/or Bifidobacteriales bacteria in samples obtained from a subject at two or more time points and administering a therapeutically effective amount of a treatment or preventive agent for high intestinal permeability to the subject when the amount of Clostridiales and/or Bifidobacteriales bacteria in the samples decreases over time.

2. The method of claim 1 , wherein the subject is a preterm infant.

3. The method of claim 2 , wherein the preterm infant is an infant of less than 37 weeks of gestational age.

4. The method of claim 1 , wherein the sample is a stool sample.

5. The method of claim 1 , wherein a decrease in IP of at least 10% compared with a subject that does not receive the treatment or preventive agent for high intestinal permeability is achieved.

6. The method of claim 1 , wherein the amount of bacteria in the sample is based on the relative abundance of one or more selected genes corresponding to the bacteria in the sample.

7. The method of claim 1 , wherein the amount of bacteria in the sample is based on the relative abundance of a 16S rRNA gene variable region of the bacteria in the sample.

8. The method of claim 1 , wherein the amount of bacteria in the sample is based on the relative abundance of the V3-V4 variable region of a 16S rRNA gene of the bacteria in the sample.

9. The method of claim 1 , wherein when samples are obtained from a subject at two or more time points in (be), the time points are separated by at least 7 days plus or minus 1 to 2 days.

10. The method of claim 1 , wherein the decrease in the amount of Clostridiales and/or Bifidobacteriales bacteria in the samples in over time in (be) is a decrease of at least about 10%.

11. The method of claim 1 , wherein the treatment is one or more of live biotherapeutic product (LBP), antibiotics, prebiotics, synbiotics, and intestinal environment parameters modifying small molecules.

12. The method of claim 1 , wherein the preventive agent is one or more of LBP, antibiotics, prebiotics, synbiotics, and intestinal environment parameters modifying small molecules.

13. The method of claim 1 , further comprising administering breast milk to the subject or reducing exposure of the subject to antibiotics, or both.

14. A method of treating or preventing high intestinal permeability in a subject comprising:
(a) determining the amount of Clostridiales bacteria in a sample obtained from a subject, and administering a therapeutically effective amount of a treatment or preventive agent for high intestinal permeability (IP) to the subject when the amount of Clostridiales and/or Bifidobacteriales bacteria in the sample is about 5% or less by relative abundance of the total amount of bacteria;
(b) determining the amount of Clostridiales bacteria in a sample obtained from a subject, and administering a therapeutically effective amount of a treatment or preventive agent for high intestinal permeability to the subject when the amount of Clostridiales and/or Bifidobacteriales bacteria is within a pre-established range of amounts of Clostridiales and/or Bifidobacteriales bacteria associated with high intestinal permeability; or
(c) determining the amount of Clostridiales bacteria in samples obtained from a subject at two or more time points and administering a therapeutically effective amount of a treatment or preventive agent for high intestinal permeability to the subject when the amount of Clostridiales and/or Bifidobacteriales bacteria in the samples decreases over time.

15. The method of claim 14 , wherein the subject is a preterm infant.

16. The method of claim 15 , wherein the preterm infant is an infant of less than 37 weeks of gestational age.

17. The method of claim 14 , wherein the sample is a stool sample.

18. The method of claim 14 , wherein a decrease in IP of at least 10% compared with a subject that does not receive the treatment or preventive agent for high intestinal permeability is achieved.

19. The method of claim 14 , wherein the amount of bacteria in the sample is based on the relative abundance of one or more selected genes corresponding to the bacteria in the sample.

20. The method of claim 14 , wherein the amount of bacteria in the sample is based on the relative abundance of a 16S rRNA gene variable region of the bacteria in the sample.

21. The method of claim 14 , wherein the amount of bacteria in the sample is based on the relative abundance of the V3-V4 variable region of a 16S rRNA gene of the bacteria in the sample.

22. The method of claim 14 , wherein when samples are obtained from a subject at two or more time points in (c), the time points are separated by at least 7 days plus or minus 1 to 2 days.

23. The method of claim 14 , wherein the decrease in the amount of Clostridiales bacteria in the samples in over time in (c) is a decrease of at least about 10%.

24. The method of claim 14 , wherein the treatment is one or more of live biotherapeutic product (LBP), antibiotics, prebiotics, synbiotics, and intestinal environment parameters modifying small molecules.

25. The method of claim 14 , wherein the preventive agent is one or more of LBP, antibiotics, prebiotics, synbiotics, and intestinal environment parameters modifying small molecules.

26. The method of claim 14 , further comprising administering breast milk to the subject or reducing exposure of the subject to antibiotics, or both.

Assignees

• Ma Bing
• Viscardi Rose
• Ravel Jacques
• Univ Maryland

Inventors

• Ma Bing
• Viscardi Rose
• Ravel Jacques

Classifications

• C12Q2600/158

  Expression markers · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q1/689 Primary

  for bacteria · CPC title

• G01N2800/067

  Pancreatitis or colitis · CPC title

• G01N2800/50

  Determining the risk of developing a disease · CPC title