Methods for modulation of dietary and microbial exposure with compositions comprising an EGFR ligand

1. A method for suppressing formation of goblet associated antigen passages (GAPs) in a human subject comprising: administering an effective amount of a composition comprising an epidermal growth factor receptor (EGFR) ligand and a diluent,

wherein

the composition does not comprise breast milk;

the EGFR ligand is administered to the subject over a time course of treatment in a multiple dosage regime;

the amount of the EGFR ligand administered decreases as the subject ages and the subject is an infant or child between about 0 days old (first day of life) and about two years old or about weaning age; and

the subject has, is suspected of having, or is at risk for an allergic disorder, and administration of the composition results in a reduced immune response.

2. The method of claim 1 , wherein the subject has an allergic disorder, and administration of the composition results in a reduced immune response.

3. The method of claim 2 , wherein the allergic disorder is a food allergy.

4. The method of claim 1 , wherein the method comprises oral administration of the composition comprising an EGFR ligand.

5. The method of claim 1 , wherein

(i) the composition comprising an EGFR ligand is administered to the subject, wherein the EGFR ligand concentration in the composition is between about 0.02 μg/mL and about 0.2 μg/mL; or

(ii) the subject is between about 0 days old (day of birth) and about 1 year old, about 18 months old, or about two years old or between 0 days of age (first day of life) and about 140 days of age.

6. The method of claim 1 , wherein the composition comprising the EGFR ligand is administered to the subject in an oral formulation.

7. The method of claim 6 , wherein the oral formulation is selected from the group consisting of a food formulation, a powdered formulation, liquid formulation, and a capsule, including wherein the oral formulation is liquid dispensed in a dropper bottle, powdered infant formula, liquid concentrate infant formula, ready-to-use infant formula, or parenteral hyperalimentation, wherein the oral formulation is optionally used to supplement infant formula or breast milk.

8. The method of claim 1 , wherein the EGFR ligand is selected from one or more of the group consisting of: EGF, transforming growth factor-a (TGFa), heparin-binding EGF-like growth factor (HB-EGF), amphiregulin (AR), betacellulin (BTC), epiregulin (EPR), hyaluronic acid, epigen, and other EGFR activator.

9. The method of claim 8 , wherein the EGFR ligand is in an effective amount to:

reduce immune response toward an antigen;

modulate exposure to gut luminal substances;

modulate colonic antigen uptake or antigen exposure;

modulate luminal antigen delivery;

reduce bacterial translocation;

promote development of regulatory T-cells restraining Th2 responses;

promote RORγt+iTreg development and maintenance; or

modulate Th2 related immunoglobulins and cytokines.

10. A method of modulating antigen passage to outside of the intestines from the gut of a human subject comprising administering to the subject an effective amount of a composition comprising an EGFR ligand and a diluent,

wherein

the composition does not comprise breast milk;

the subject has, is suspected of having, or is at risk of developing an allergic disorder;

the EGFR ligand is administered to the subject over a time course of treatment in a multiple dosage regime and the amount of the EGFR ligand administered decreases as the subject ages; and

the subject is an infant or child between about 0 days old (first day of life) and about two years old or about weaning age.

11. The method of claim 10 , wherein the EGFR ligand is in an effective amount to treat, prevent, or reduce the likelihood of developing a food allergy and the composition comprising an EGFR ligand is administered to the intestine.

12. The method of claim 10 , wherein the composition is formulated in an oral formulation selected from the group consisting of: a food formulation, a powdered formulation, liquid formulation, and a capsule, including wherein the oral formulation is liquid dispensed in a dropper bottle, powdered infant formula, liquid concentrate infant formula, ready-to-use infant formula, or parenteral hyperalimentation, wherein the oral formulation is optionally used to supplement infant formula or breast milk.

13. The method of claim 10 , wherein the EGFR ligand is selected from one or more of the group consisting of: EGF, transforming growth factor-a (TGFa), heparin-binding EGF-like growth factor (HB-EGF), amphiregulin (AR), betacellulin (BTC), epiregulin (EPR), hyaluronic acid, epigen, and other EGFR activator.

14. The method of claim 10 , wherein the EGFR ligand is in an effective amount to:

reduce immune response toward an antigen;

modulate exposure to gut luminal substances;

reduce bacterial translocation;

modulate colonic antigen uptake or antigen exposure;

modulate luminal antigen delivery;

promote development of regulatory T-cells restraining Th2 responses;

promote RORγt+iTreg development and maintenance; or

modulate Th2 related immunoglobulins and cytokines.

15. A method for treating or reducing the likelihood of developing a food allergy in a human subject in need thereof, the method comprising: administering to the intestine an effective amount of a composition comprising an EGFR ligand and a diluent to the subject, wherein

the composition does not comprise breast milk;

the EGFR ligand is administered to the subject over a time course of treatment in a multiple dosage regime;

the amount of the EGFR ligand administered decreases as the subject ages; and

the subject is an infant or child between about 0 days old (first day of life) and about two years old or about weaning age.

16. The method of claim 15 , wherein the EGFR ligand is selected from one or more of the group consisting of: EGF, transforming growth factor-a (TGFa), heparin-binding EGF-like growth factor (HB-EGF), amphiregulin (AR), betacellulin (BTC), epiregulin (EPR), hyaluronic acid, epigen, and other EGFR activator.

17. A method for suppressing formation of goblet associated antigen passages (GAPs) in a human subject or modulating antigen passage to outside of the intestines from the gut of a human subject comprising: administering to the intestine an oral formulation comprising a composition comprising an epidermal growth factor receptor (EGFR) ligand and a diluent,

wherein

the composition does not comprise breast milk;

the EGFR ligand is administered to the subject over a time course of treatment in a multiple dosage regime;

the amount of the EGFR ligand administered decreases as the subject ages and the subject is an infant or child between about 0 days old (first day of life) and about two years old or about weaning age;

the subject has, is suspected of having, or is at risk for necrotizing enterocolitis (NEC) or sepsis; and

administration of the composition results in a reduced immune response.

18. The method of claim 17 , wherein the EGFR ligand is in an effective amount to treats, prevents, or reduce the likelihood of developing NEC.

19. The method of claim 17 , wherein

(i) the composition comprising an EGFR ligand is administered to the subject, wherein the EGFR ligand concentration in the composition is between about 0.02 μg/mL and about 0.2 μg/mL; or

(ii) the subject is between about 0 days old (day of birth) and about 1 year old, about 18 months old, or about two years old or between 0 days of age (first day of life) and about 140 days of age.

20. The method of claim 17 , wherein the oral formulation is selected from the group consisting of a food formulation, a powdered formulation, liquid formulation, and a capsule, including wherein the oral formulation is liquid dispensed in a dropper bottle, powdered infant formula, liquid concentrate infant formula, ready-to-use infant formula, or parenteral hyperalimentation, wherein the oral formulation is optionally used to supplement infant formula or breast milk.

21. The method of claim 17 , wherein the EGFR ligand is selected from one or more of the group consisting of: EGF, transforming growth factor-a (TGFa), heparin-binding EGF-like growth factor (HB-EGF), amphiregulin (AR), betacellulin (BTC), epiregulin (EPR), hyaluronic acid, epigen, and other EGFR activator.

22. The method of claim 17 , wherein the EGFR ligand is in an effective amount to:

reduce immune response toward an antigen;

modulate exposure to gut luminal substances;

modulate colonic antigen uptake or antigen exposure;

modulate luminal antigen delivery;

reduce bacterial translocation;

promote development of regulatory T-cells restraining Th2 responses;

promote RORγt+iTreg development and maintenance; or

modulate Th2 related immunoglobulins and cytokines.

23. The method of claim 17 , wherein the subject is at risk of sepsis.

24. The method of claim 17 , wherein the subject is at risk for NEC.

25. The method of claim 17 , wherein the sepsis is late onset sepsis (LOS).

26. The method of claim 17 , wherein the subject is a pre-term infant or neonate.

27. The method of claim 17 , wherein the dosage is administered until the subject is 60 days old.