Search

EP-4739149-A1 - COMBINATION FOR DIETARY MANAGEMENT OF GUT HEALTH

EP4739149A1EP 4739149 A1EP4739149 A1EP 4739149A1EP-4739149-A1

Abstract

The present invention provides a combination comprising lactose and human milk oligosaccharides (HMOs) 2'-fucosyllactose (2'-FL), lacto-/V-neotetraose (LNnT), 3- fucosyllactose (3'-FL), at least one of 3'-sialyllactose (3'-SL) or 6'-sialyllactose (6'-SL), and optionally lacto-N-tetraose (LNT) for use in the dietary management of dysbiosis of the gut microbiota in a subject or for use in the dietary management of a disease or disorder associated with metabolism and/or accumulation of BCFA in a subject.

Inventors

  • NUTTEN, Sophie Hélène
  • HEINE, Ralf
  • Favre, Laurent

Assignees

  • Société des Produits Nestlé S.A.

Dates

Publication Date
20260513
Application Date
20240628

Claims (19)

  1. 1. A combination comprising lactose and human milk oligosaccharides (HMOs) 2'- fucosyllactose (2’-FL), lacto-/V-neotetraose (LNnT), 3-fucosyllactose (3’-FL), and at least one of 3’-sialyllactose (3’-SL) or 6’-sialyllactose (6’-SL) for use in (a) the dietary management of dysbiosis of the gut microbiota in a subject; (b) the dietary management of a disease or disorder associated with metabolism and/or accumulation of branched chain fatty acids (BCFA) in a subject; or (c) the reduction of BCFA in a subject.
  2. 2. The combination for use according to claim 1 , wherein the composition comprises the HMOs 2’-FL, LNnT, 3’-FL, 3’-SL, 6’-SL, and lacto-N-tetraose (LNT).
  3. 3. The combination for use according to claim 1 or claim 2, wherein the combination is for use in the dietary management of dysbiosis of the gut microbiota, and wherein the dysbiosis includes increased production of BCFA, such as isobutyrate, isovalerate, and/or isocaproate.
  4. 4. The combination for use according to any one of claims 1 to 3, wherein the combination is for use in the dietary management of dysbiosis of the gut microbiota in a subject, and wherein the dysbiosis of the gut microbiota is associated with an intestinal disorder and/or an extra- intestinal disorder; optionally wherein the intestinal disorder is one or more of inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and coeliac disease and/or wherein the extra-intestinal disorder is one or more of allergy, asthma, atopic dermatitis, metabolic syndrome, cardiovascular disease, obesity, and type 2 diabetes.
  5. 5. The combination for use according to claim 1 or claim 2, wherein the combination is for use in the dietary management of a disease or disorder associated with metabolism and/or accumulation of branched chain fatty acids (BCFA), and (a) wherein the BCFA comprise isobutyrate, isovalerate, and/or isocaproate; and/or (b) wherein the disease or disorder associated with metabolism of BCFA is increased proteolytic fermentation and/or decreased saccharolytic fermentation.
  6. 6. A combination comprising lactose and HMOs 2’-FL, LNnT, 3’-FL, and at least one of 3’- SL or 6’-SL for use in the dietary management of (a) a pathogen in a subject; (b) a pathogen in a subject, wherein the pathogen is one or more of bacterial, viral or protozoal pathogen; (c) a pathogen in a subject, wherein the pathogen is one or more viral pathogens, preferably rotavirus or norovirus; or (d) a pathogen in a subject, wherein the pathogen is one or more bacterial pathogens, preferably C. difficile, C. perfringens, Campylobacter or Escherichia coir, preferably wherein the subject is an infant, young child or child who has not been breastfed or wherein breast-feeding has been halted.
  7. 7. The combination for use according to claim 6, comprising the composition comprises the HMOs 2’-FL, LNnT, 3’-FL, 3’-SL, 6’-SL, and LNT.
  8. 8. The combination for use according to claim 6 or claim 7, wherein (a) the pathogen is at least one of C. difficile and C. perfringens’, or (b) the pathogen is at least one of C. difficile and C. perfringens, and wherein there is a resolution or reduction in one or more symptoms associated with an overgrowth of C. difficile and/or C. perfringens, preferably wherein the symptom is at least one of diarrhoea and fever.
  9. 9. The combination for use according to any preceding claim, wherein the combination of lactose and HMOs reduces levels of BCFA in the gut of the subject; optionally wherein the BCFA comprise isobutyrate, isovalerate, and/or isocaproate.
  10. 10. The combination for use according to any one of claims 1 to 9, comprising the HMOs 2’- FL (about 0.8-1.2 g/L of the combination as consumed), 3’-FL (about 0.4-0.6 g/L of the combination as consumed), LNnT (about 0.4-0.6 g/L of the combination as consumed); 3’-SL (about 0.08-0.12 g/L of the combination as consumed), 6’-SL (about 0.16-0.24 g/L of the combination as consumed), and LNT (about 0.24-0.36 g/L of the combination as consumed).
  11. 11. The combination for use according to any one of the preceding claims, wherein the combination is provided in the form of a nutritional composition and wherein the nutritional composition is an infant formula, a starter infant formula, a follow-on or follow-up infant formula or a growing-up milk, preferably an infant formula.
  12. 12. The combination for use according to any one of claims 1 to 10 or the nutritional composition for use according to claim 11 , wherein the HMOs in the combination or nutritional composition comprise or consist of, with reference to the total amount of HMOs in the combination or nutritional composition: i. the HMOs 2’-FL, LNnT, 3’-FL, 3’-SL, and 6’SL comprising or consisting of: a. about 22 wt % to about 65 wt % of 2’-FL, preferably about 35 wt % to about 52 wt %, preferably about 43 wt %; b. about 11 wt % to about 33 wt % of LNnT, preferably about 17 wt % to about 26 wt %, preferably about 22 wt %; c. about 11 wt % to about 33 wt % 3’-FL, preferably about 17 wt % to about 26 wt %, preferably about 22 wt %; d. about 2 wt % to about 7 wt % of 3’-SL; preferably about 3 wt % to about 5 wt %, preferably about 4 wt %; and e. about 4 wt % to about 13 wt % of 6’-SL, preferably about 7 wt % to about 10 wt %, preferably about 9 wt %; ii. the HMOs 2’-FL, LNnT, 3’-FL, and one of 3’-SL or 6’SL comprising or consisting of: a. about 22 wt % to about 65 wt % of 2’-FL, preferably about 35 wt % to about 52 wt %, preferably about 43 wt %; b. about 11 wt % to about 33 wt % of LNnT, preferably about 17 wt % to about 26 wt %, preferably about 22 wt %; c. about 11 wt % to about 33 wt % 3’-FL, preferably about 17 wt % to about 26 wt %, preferably about 22 wt %; and d. about 2 wt % to about 7 wt % of 3’-SL; preferably about 4 wt % to about 6 wt %, preferably about 5 wt %; or about 5 wt % to about 14 wt % of 6’-SL, preferably about 7 wt % to about 11 wt %, preferably about 9 wt %; iii. the HMOs 2’-FL, LNnT, 3’-FL, 3’-SL, 6’SL and LNT comprising or consisting of: a. about 19 wt % to about 58 wt % of 2’-FL, preferably about 31 wt % to about 46 wt %, preferably about 38 wt %; b. about 10 wt % to about 29 wt % of LNnT, preferably about 15 wt % to about 23 wt %, preferably about 19 wt %; c. about 10 wt % to about 29 wt % 3’-FL, preferably about 15 wt % to about 23 wt %, preferably about 19 wt %; d. about 2 wt % to about 6 wt % of 3’-SL; preferably about 3 wt % to about 5 wt %, preferably about 4 wt %; e. about 54 wt % to about 12 wt % of 6’-SL, preferably about 6 wt % to about 9 wt %, preferably about 8 wt %; and f. about 6 wt % to about 17 wt % of LNT, preferably about 9 wt % to about 14 wt %, preferably about 12 wt %.
  13. 13. The nutritional composition for use according to claim 12, comprising the HMOs 2’-FL (about 0.8-1 .2 g/L of the composition as consumed), 3’-FL (about 0.4-0.6 g/L of the composition as consumed), LNnT (about 0.4-0.6 g/L of the composition as consumed); 3’-SL (about 0.08- 0.12 g/L of the composition as consumed), 6’-SL (about 0.16-0.24 g/L of the composition as consumed), and LNT (about 0.24-0.36 g/L of the composition as consumed).
  14. 14. The combination for use according to any one of claims 1 to 10 or the nutritional composition for use according claim 12 or claim 13, comprising (a) lactose in an amount of about 23-50 g/L or 29-44 g/L of the combination or nutritional composition as consumed; (b) lactose in an amount of about 37 g/L of the combination as consumed; (c) lactose in an amount of about 58-88 g/L or 65-80 g/L of the combination or composition as consumed; or (d) lactose in an amount of about 73 g/L of the combination or composition as consumed.
  15. 15. The combination or nutritional composition for use according to any one of the preceding claims, wherein the combination or nutritional composition further comprises butyrate (a) in an amount from about 1 mg/L to about 30 mg/L of the combination or nutritional composition as consumed; (b) in an amount of from about 1.6 mg/L to about 2.4 mg/L of the combination or nutritional composition as consumed, or from about 8 mg/L to about 12 mg/L of the combination or nutritional composition as consumed, or from about 16 mg/L to about 24 mg/L of the combination or nutritional composition as consumed; (c) in an amount of from about from about 16 mg/L to about 24 mg/L of the composition or nutritional composition as consumed; or (d) in an amount of about 20 mg/L of the composition or nutritional composition as consumed.
  16. 16. The combination for use according to any one of claims 1 to 10, 14 and 15 or the nutritional composition for use according to any one of the claims 12 to 15, wherein the combination or nutritional composition further comprises (a) a compound having the formula: or combinations thereof as a source of dietary butyrate; wherein each of R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are oleic acid; or (b) a triglyceride composed of a mixture of butyric acid (C4:0) and caprylic acid (C8:0) as a source of dietary butyrate.
  17. 17. The combination for use according to claim 16 or the nutritional composition for use according to claim 16, wherein the combination or nutritional composition comprises the equivalent of (a) from about 1 mg/L to about 30 mg/L of the combination or nutritional composition as consumed; (b) from about 1.6 mg/L to about 2.4 mg/L of the combination or nutritional composition as consumed, or from about 8 mg/L to about 12 mg/L of the combination or nutritional composition as consumed, or from about 16 mg/L to about 24 mg/L of the combination or nutritional composition as consumed; (c) about 30 mg/L dietary butyrate in the combination or nutritional composition as consumed; (d) about 16-24 mg/L dietary butyrate in the combination or nutritional composition as consumed; or (e) about 20 mg/L dietary butyrate in the combination or nutritional composition as consumed.
  18. 18. The combination or nutritional composition for use according to any one of the preceding claims wherein the combination or nutritional composition further comprises one or more bacterium of the genera Bifidobacterium and/or Lactobacillus.
  19. 19. The combination or nutritional composition defined according to any one of the preceding claims for use in the dietary management of cow’s milk protein allergy (CM PA).

Description

COMBINATION FOR DIETARY MANAGEMENT OF GUT HEALTH FIELD OF THE INVENTION The present invention relates to compositions, particularly a nutritional composition, and methods for the dietary management of gut health; for example in an infant. BACKGROUND TO THE INVENTION Mother's milk is recommended for all infants. However, in some cases breast feeding is inadequate or unsuccessful for medical reasons or the mother chooses not to breast feed. Nutritional compositions such as infant formulae have been developed for these situations. Nutritional compositions for infants and young children are often sold as powders to be reconstituted with water or in some instances as ready to drink or concentrated liquid compositions. Those compositions are intended to cover most or all of the nutritional needs of the infants or young children. Infant formula manufacturers have therefore made many attempts to induce nutritional health effects close to or similar to the benefits of human breast milk. However, many studies have shown that infant formula do not induce the identical effects on the body compared to human breast milk. For example, infants fed infant formula and infants fed human-breast milk (HBM) can exhibit a different intestinal (gut) microbiota. HMOs (human milk oligosaccharides) have become the subject of much interest in recent years due to their roles in numerous biological processes occurring in the human organism. Mammalian milk contains at least 130 of these complex oligosaccharides (Urashima et al, Milk Oligosaccharides, Nova Biomedical Books, New York, 2011 , ISBN: 978-1-61122-831-1). Evidence is accumulating that the resident community of microbes, called the microbiota, in the human digestive tract plays a major role in health and disease. When the composition of the intestinal microbiota is thrown off balance, the host can suffer consequences. Recent research has implicated intestinal microbiota imbalances in individual disorders as diverse as cancer, obesity, inflammatory bowel disease, psoriasis, asthma, and possibly even autism. Infancy, especially the first weeks, 3 months, 6 months or 12 months of life is a critical period for the establishment of a balanced gut microbiota. It is known that the modulation of the gut microbiota during infancy can prospectively have a significant influence in the future health status of the body. For example, the gut microbiome can have an influence on the development of a strong immune system later in life, as well as normal growth, and even on the development of obesity or allergy later in life. Thus, there is a demand for new nutritional interventions for the dietary management of gut health, for example in an infant, in particular where the infant is formula-fed. SUMMARY OF THE INVENTION The present inventors have surprisingly found that a combination of lactose and specific combinations of human milk oligosaccharides (HMO) synergistically promote beneficial effects for infant gut health, for example by reducing levels of branched chain fatty acids (BCFA). BCFA that are indicative of proteolytic fermentation by the gut microbiota and are associated with the formation of metabolites such as phenol and indole that exert detrimental health effects. Compositions that reduce and/or limit BCFA production may thus have beneficial effects on infant gut health. In one aspect, the present invention provides a combination comprising lactose and human milk oligosaccharides (HMOs) 2'-fucosyllactose (2’-FL), lacto-ZV-neotetraose (LNnT), 3’-fucosyllactose (3'-FL), at least one of 3’-sialyllactose (3’-SL) or 6’-sialyllactose (6’-SL), and optionally lacto-ZV-tetraose (LNT) for use in the dietary management of dysbiosis of the gut microbiota in a subject. In a related aspect, the present invention provides a combination comprising lactose and HMOs 2’-FL, LNnT, 3'-FL, LNT, 3’-SL, and 6’-SL for use in the dietary management of dysbiosis of the gut microbiota in a subject. In another aspect, the present invention provides a combination comprising lactose and HMOs 2’-FL, LNnT, 3’-FL, at least one of 3’-SL or 6’-SL, and optionally LNT for use in the dietary management of a disease or disorder associated with metabolism and/or accumulation of BCFA in a subject. In a related aspect, the present invention provides a combination comprising lactose and HMOs 2’-FL, LNnT, 3’-FL, 3’-SL, 6’-SL, and LNT for use in the dietary management of a disease or disorder associated with metabolism and/or accumulation of BCFA in a subject. In a further aspect, the invention provides a combination comprising lactose and HMOs 2’-FL, LNnT, 3’-FL, at least one of 3’-SL or 6’-SL, and optional LNT for use in the dietary management of at least one pathogen, preferably a pathogenic bacteria, in a subject. In a related aspect, the present invention provides a combination comprising lactose and HMOs 2’-FL, LNnT, 3’-FL, 3’- SL, 6’-SL, and LNT for use in in the dietary management of at least one pathogen, preferably