Human milk oligosaccharides to promote growth of beneficial gut bacteria

• US 8,197,872 B2
• Filed: 05/15/2008
• Issued: 06/12/2012
• Est. Priority Date: 05/17/2007
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Mills, David A., Lebrilla, Carlito B., LoCascio, Riccardo, Ninonuevo, Milady, German, J. Bruce, Freeman, Samara
• Primary Examiner(s): Tarazano, D. Lawrence
• Assistant Examiner(s): Badr, Hamid R
• Application Number:
  US12/121,683
• Publication Number:
  US 20090098240A1
• Time in Patent Office: 1,489 Days
• Field of Search: 426/3, 426/580, 426/61, 426/583
• US Class Current: 426/3
• CPC Class Codes: A23C 9/203 containing bifidus-active substances, e.g. lactulose; containing oligosaccharides
• CPC Class Codes: A23G 4/10 characterised by the carbohydrates used, e.g. polysaccharides containing dairy products A23G4/16

Abstract

The present invention provides prebiotic and probiotic compositions containing human milk oligosaccharides and methods of use that selectively promote the growth of beneficial gut bacteria.

Claims

1. A synthetic prebiotic composition comprising a first, second and third purified oligosaccharide each of which naturally occur in human breast milk, wherein the first oligosaccharide has a mass/charge (m/z) ratio of about 732.3;

the second oligosaccharide has a mass/charge (m/z) ratio of about 1243.4; and

the third oligosaccharide has a mass/charge (m/z) ratio of about 1389.5,

wherein the m/z ratio is measured by matrix-assisted laser desorption/ionization (MALDI), and

wherein the composition is consumed at a higher rate by Bifidobacterium longum bv. infantis (B. infantis) compared to other Bifidobacterium strains.

2. The synthetic prebiotic composition of claim 1, where in the first oligosaccharide is selected from the group consisting of Lacto-N-tetraose and Lacto-N-neotetraose;

the second oligosaccharide is selected from the group consisting of Monofucosyllacto-N-hexaose, Isomeric Fucosylated Lacto-N-hexaose (1), Isomeric Fucosylated Lacto-N-hexaose (2), Isomeric Fucosylated Lacto-N-hexaose (3); and

the third oligosaccharide is selected from the group consisting of Difucosyl-para-lacto-neohexaose, Difucosyl-para-lacto-hexaose, and Difucosyl lacto-hexaose.

3. The synthetic prebiotic composition of claim 1, further comprising a fourth oligosaccharide that naturally occurs in human breast milk and has a mass/charge (m/z) ratio of about 1097.4.

4. The synthetic prebiotic composition of claim 3, wherein the fourth oligosaccharide is selected from the group consisting of Lacto-N-hexaose, Lacto-N-neohexaose, Para-lacto-hexaose, and Para-lacto-neohexaose.

5. The synthetic prebiotic composition of claim 3, further comprising a fifth oligosaccharide that naturally occurs in human breast milk and has a mass/charge (m/z) ratio of about 878.3.

6. The synthetic prebiotic composition of claim 5, wherein the fifth oligosaccharide is selected from the group consisting of Lacto-N-fucopentaose I, Lacto-N-fucopentaose II, Lacto-N-fucopentaose III, and Lacto-N-fucopentaose IV.

7. The synthetic prebiotic composition of claim 1, further comprising an inoculum of B. infantis.

8. The synthetic prebiotic composition of claim 1, further comprising a bovine milk protein, a soy protein, betalactoglobulin, whey, soybean oil or starch.

9. The synthetic prebiotic composition of claim 1, wherein said prebiotic composition is in the form of a powder, a tablet, a capsule, a lozenge, a chewing gum, a food product, or a supplemented beverage.

10. The synthetic prebiotic composition of claim 9, wherein said supplemented beverage is a member selected from the group consisting of an infant formula, follow-on formula, toddler'"'"'s beverage, milk, fruit juice, and fruit-based drink.

11. The synthetic prebiotic composition of claim 1, wherein said first, second and third oligosaccharide are each at a concentration of 100 micrograms/L to 25 grams/L.

16. A method of producing a synthetic prebiotic food product or food supplement, the method comprising, combining at least one food ingredient with the first and second and third oligosaccharide of claim 1, thereby generating a prebiotic food product or food supplement.

17. The method of claim 16, wherein the food ingredient comprises a bovine milk protein, a soy protein, betalactoglobulin, whey, soybean oil or starch.

18. The method of claim 16, further comprising combining an inoculum of B. infantis with the food ingredient and/or first and second and third oligosaccharide.

19. The method of claim 16, wherein at least one of the first, second and third oligosaccharides are synthesized before the combining step.

20. The method of claim 16, wherein at least one of the first, second and third oligosaccharides are purified before the combining step.

12. A synthetic prebiotic composition comprising at least three purified oligosaccharides that naturally occur in human breast milk, wherein the oligosaccharides have a mass/charge (m/z) ratio selected from the group consisting of about 878.3, about 1097.4, about 1243.4, about 1389.5, about 1462.5, about 1608.6, about 1754.6, about 1827.6, and about 1900.7,

wherein the m/z ratio is measured by matrix-assisted laser desorption/ionization (MALDI), and

wherein the composition is consumed at a higher rate by Bifidobacterium longum bv. infantis (B. infantis) compared to other Bifidobacterium strains.

13. The synthetic prebiotic composition of claim 12, wherein the oligosaccharides are selected from the group consisting of Lacto-N-Tetraose, Lacto-N-Neotetraose, Lacto-N-Fucopentaose I, Lacto-N-Fucopentaose II, Lacto-N-Fucopentaose III, Lacto-N-Fucopentaose V, Lacto-N-Hexaose, Para-Lacto-N-Hexaose, Lacto-N-Neohexaose, Para-Lacto-N-Neohexaose, Monofucosyllacto-N-Hexaose II, Isomeric Fucosylated Lacto-N-Hexaose (1), Monofucosyllacto-N-Hexaose, Isomeric Fucosylated Lacto-N-Hexaose (3), Isomeric Fucosylated Lacto-N-Hexaose (2), Difucosyl-Para-Lacto-N-Neohexaose, Difucosyl-Para-Lacto-N-Hexaose, Difucosyllacto-N-Hexaose, Lacto-N-Neoocataose, Para-Lacto-N-Octanose, Iso-Lacto-N-Octaose, Lacto-N-Octaose, Monofucosyllacto-N-neoocataose, Monofucosyllacto-N-Ocataose, Difucosyllacto-N-Octaose I, Difucosyllacto-N-Octaose II, Difficosyllacto-N-Neoocataose II, Difucosyllacto-N-Neoocataose I, Lacto-N-Decaose, Trifucosyllacto-N-Neooctaose, Trifucosyllacto-N-Octaose and Trifucosyl-Iso-Lacto-N-Octaose.

14. The synthetic prebiotic of claim 12 or 13, comprising at least two, at least three, at least four or at least five oligosaccharides selected from the group.

15. The synthetic prebiotic composition of claim 12, further comprising an inoculum of B. infantis.