Search

EP-4734774-A1 - NUTRITIONAL COMPOSITION COMPRISING UREA, NON-DIGESTIBLE OLIGOSACCHARIDE, AND BIFIDOBACTERIA

EP4734774A1EP 4734774 A1EP4734774 A1EP 4734774A1EP-4734774-A1

Abstract

The invention relates to nutritional compositions for infants and in particular formulae for infants comprising human milk oligosaccharides, specific bifidobacteria, and urea as non-protein nitrogen source for improving the intestinal microbiota.

Inventors

  • VAN LIMPT, CORNELUS JOHANNES PETRUS
  • BONGERS, Roger

Assignees

  • N.V. Nutricia

Dates

Publication Date
20260506
Application Date
20240627

Claims (20)

  1. 1 . A nutritional composition comprising urea, non-digestible oligosaccharide, and lactic acid producing bacteria, wherein the non-digestible oligosaccharide comprises one or more human milk oligosaccharides selected from the group consisting of 2’-fucosyllacose (2’-FL), 3-fucosyllactose (3-FL), 3’-sialyllactose (3’-SL), and 6’-sialyllactose (6’-SL), and wherein the lactic acid producing bacteria comprise a strain of Bifidobacterium longum ssp infantis able to express urease, and a strain of Bifidobacterium bifidum able to express at least one extracellular enzyme selected from a fucosidase and a sialidase and not able to express a urease.
  2. 2. The nutritional composition according to claim 1 , comprising 2’-fucosyllactose, preferably comprising at least 0.01 g/100 ml 2’-fucosyllactose, preferably 0.01 g/100 ml to 1 g/100 ml 2’- fucosyllactose.
  3. 3. The nutritional composition according to any one of the preceding claims, wherein the non- digestible oligosaccharide further comprises beta-galacto-oligosaccharides comprising beta1 ,4 linkages and having a degree of polymerization of at least 4.
  4. 4. The nutritional composition according to any one of the preceding claims, which further comprises a strain of Bifidobacterium breve able to express an extracellular betal ,4 endogalactanase and that preferably is not able to express fucosidase and is not able to express sialidase.
  5. 5. The nutritional composition according to any one of the preceding claims, wherein the non- digestible oligosaccharide further comprises non-digestible polyfructose, preferably with an average degree of polymerization of at least 11 .
  6. 6. The nutritional composition according to any one of the preceding claims, comprising at least four, preferably at least five human milk oligosaccharides selected from the group consisting of 2’-fucosyllactose, 3-fucosyllactose, 3’-sialyllactose, 6’-sialyllactose, lacto-N-tetraose, lacto-N-neotetraose and difucosyllactose.
  7. 7. The nutritional composition according to any one of the preceding claims, wherein the urea is present in an amount of at least 15 mg per 100 ml, preferably 15 to 75 mg per 100 ml, and/or at least 0.1 1 wt% based on dry weight of the composition, preferably 0.11 wt% to 0.55 wt%, based on dry weight of the composition, and/or at least 22 mg, preferably 22 to 112 mg per 100 kcal.
  8. 8. The nutritional composition according to any one of the preceding claims further comprising protein, digestible carbohydrate and lipid.
  9. 9. The nutritional composition according to claim 8 which is an infant formula, a follow on formula or a young child formula, preferably an infant formula.
  10. 10. The nutritional composition according to any one of claims 8 to 9, wherein the urea is present at least 1.13 wt%, preferably 1 .13 to 5.6 wt%, based on total protein.
  11. 11 . The nutritional composition according to any one of claims 8 to 10 comprising 1 .0 to 2.1 g protein per 100 kcal.
  12. 12. The nutritional composition according to any one of claims 8 to 11 comprising at least 90 wt% cow’s milk proteins based on total protein.
  13. 13. The nutritional composition according to any one of the preceding claims comprising at least 0.01 g/100 ml human milk oligosaccharide, preferably 0.01 to 1 .5 g per 100 ml, and/or at least 0038 wt% based on dry weight of the composition, preferably 0.038 wt% to 12 wt.% based on dry weight of the composition, and/or 0.015 g per 100 kcal, preferably 0.015 to 2.5 g per 100 kcal.
  14. 14. The nutritional composition according to any one of claims 3 to 13 wherein the amount of galactooligosaccharide comprising beta1 ,4 linkages having a DP of at least 4 is at least 0.05 mg/100 ml, and/or 0.35 wt% based on dry weight of the composition, and/or preferably at least 0.07 g per 100 kcal.
  15. 15. The nutritional composition according to anyone of the preceding claim, wherein the non-digestible oligosaccharides are present an amount of at least 1 .5 wt%, preferably 1 .5 wt% to 15 wt%, based on dry weight of the composition, and/or at least 0.2 g per 100 ml, preferably 0.2 g to 2 g per 100 ml, and/or 0.3 g per 100 kcal, preferably 0.3 g to 3 g per 100 kcal.
  16. 16. The nutritional composition according to any one of the preceding claims that contains at least 10 5 cfu B. longum ssp infantis able to express a urease, per gram dry weight of the nutritional composition and at least 10 5 cfu B. bifidum able to express at least one extracellular enzyme selected from a fucosidase and a sialidase and not to able to express a urease, and optionally at least 10 5 cfu B. breve able to express beta1 ,4 endogalactanase, per gram dry weight of the nutritional composition, and wherein the total amount of bifidobacteria is at least 10 6 cfu per gram dry weight of the nutritional composition.
  17. 17. The nutritional composition according to any one of the preceding claims, for use in increasing the level and/or metabolic activity of intestinal bifidobacteria, preferably in a child, preferably in an infant.
  18. 18. The nutritional composition according to any one of claims 1-16, for use in preventing and/or treating intestinal microbial dysbiosis and/or for use in reducing intestinal pathogenic bacteria, preferably in a child, preferably in an infant.
  19. 19. The nutritional composition for use according to claim 18, which is in a human subject suffering from or being at risk of intestinal microbial dysbiosis, preferably selected from the group consisting of a subject that was born preterm, a subject that was born via caesarean section, a subject that is or has been treated with antibiotics and a subject that is or has been at least partly breastfed by a woman taking antibiotics.
  20. 20. The nutritional composition according to any one of claims 1-16, for use in preventing and/or treating a disorder associated with a compromised intestinal microbiota in infants or young children.

Description

NUTRITIONAL COMPOSITION COMPRISING UREA, NON-DIGESTIBLE OLIGOSACCHARIDE, AND BIFIDOBACTERIA FIELD OF THE INVENTION The present invention relates to nutritional compositions for infants and in particular formulae for infants comprising human milk oligosaccharides, bifiobacteria, and non-protein nitrogen sources for improving the intestinal microbiota. BACKGROUND OF THE INVENTION The human gut harbors a complex microbial ecosystem, the intestinal microbiota, which has been recognized as an essential part of our human physiology. In human adults the intestinal microbiota is considered to be a stable ecosystem, hence the microbial colonization process in early-life, which is heavily intertwined with the maturation of the gastrointestinal tract itself, can be considered as fundamental step in healthy development. Early-life nutrition is a major factor that impacts the developing intestinal microbiota community and breastfeeding infants provides for an optimal intestinal microbiota dominated by Bifidobacterium species. As a consequence, breastfeeding has been associated with a multitude of health benefits related to for example infections, inflammation, allergy, eczema, diarrhea, constipation and so on. In some cases breastfeeding is inadequate or unsuccessful for medical reasons, or because of a choice not to breastfeed. For such situations infant and follow on formulae have been developed. Commercial infant formulae are commonly used today to provide supplemental or the sole source of nutrition early in life. These formulae comprise a range of nutrients to meet the nutritional needs of the growing infant, and typically include fat, carbohydrate, protein, vitamins, minerals, and other nutrients helpful for optimal infant growth and development. Commercial infant formulae are designed to mimic, as closely as possible, the composition of human milk and at least equally important mimic as good as possible the function of human milk. In order to positively affect the intestinal microbiota, infant formulae have been developed that include probiotics, hence bifidobacteria themselves, or prebiotics, in particular non-digestible oligosaccharides that promote the growth of intestinal microbiota, or that include both, such as for example is disclosed in WO 2005/110121. Protein and amino acid supplementation to develop a healthy microbiota ecosystem have also been suggested, such as for instance disclosed in EP 1638418. Infant formulae are often based on cow’s milk. Cow’s milk comprises more protein and less non-protein nitrogen (NPN), such as urea, compared to human milk. In addressing this difference GB 993,719 discloses a specific process to produce an infants' milk which includes the addition of urea to be closer to human milk. DD 208 542 is concerned with providing more breast milk-like bifidogenic nutrition based on cow’s milk by diluting standard formula based on cow’s milk to decrease the protein content and supplementing this with lactose and urea. WO 2015/105616 discloses pediatric nutritional compositions comprising a protein source comprising an intact milk protein and a partially hydrolyzed milk protein, wherein about 5% to about 25% of total nitrogen content of the composition is non-protein nitrogen. The focus of NPN here is on small peptides and amino acids and not on urea. WO 2020/089463 discloses formulae comprising a combination of urea and non-digestible oligosaccharides, for improved stimulation of the growth of bifidobacteria in the intestinal microbiota of infants or young children. Walsh et al, 2022, Scientific reports, 12, 4143, discloses a combination of the specific strains B. bifidum R0071 , B. infantis R0033, B. infantis M-63 and B breve M-16V to have a synergistic effect when grown on human milk oligosaccharides. Still there is a need for further improvement of developing a beneficial intestinal microbiota and improving the intestinal microbial resilience in particular early in life in subjects suffering from or being at risk of intestinal microbial dysbiosis. SUMMARY OF THE INVENTION The inventors found that a combination of urea, human milk oligosaccharide selected from fucosyllactoses and sialyllactoses, and a combination of a Bifidobacterium longum ssp infantis that is urease positive with a urease negative Bifidobacterium bifidum that is able to hydrolyze externally fucosyllactose and sialyllactose improved the fermentation by and growth of bifidobacteria in a synergistic manner. This synergy was not observed in the absence of urea. Therefore, a nutritional composition comprising such human milk oligosaccharides, urea and bifidobacteria beneficially further improves the microbiota and related health effects in infants or young children. DETAILED DESCRIPTION OF THE INVENTION The invention thus concerns a nutritional composition comprising urea, non-digestible oligosaccharide, and lactic acid producing bacteria, wherein the non-digestible oligosaccharide comprises one or more human milk o