WO2011136637A1 - Use of human milk oligosaccharides in infant nutrition - Google Patents

Use of human milk oligosaccharides in infant nutrition Download PDF

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Publication number
WO2011136637A1
WO2011136637A1 PCT/NL2010/050240 NL2010050240W WO2011136637A1 WO 2011136637 A1 WO2011136637 A1 WO 2011136637A1 NL 2010050240 W NL2010050240 W NL 2010050240W WO 2011136637 A1 WO2011136637 A1 WO 2011136637A1
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oligosaccharides
milk
lewis
infant
blood
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PCT/NL2010/050240
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English (en)
French (fr)
Inventor
Bernd Stahl
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N.V. Nutricia
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Priority to PCT/NL2010/050240 priority Critical patent/WO2011136637A1/en
Priority to CN2011800317016A priority patent/CN102946742A/zh
Priority to PL11720600T priority patent/PL2563166T3/pl
Priority to EP14168113.0A priority patent/EP2767173A1/de
Priority to CN201610818346.1A priority patent/CN106509916A/zh
Priority to ES11720600.3T priority patent/ES2490269T3/es
Priority to PCT/NL2011/050286 priority patent/WO2011136648A1/en
Priority to EP11720600.3A priority patent/EP2563166B1/de
Publication of WO2011136637A1 publication Critical patent/WO2011136637A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12Antidiarrhoeals
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention is in the field of tailor-made infant nutrition, depending on the blood group or blood type of the mother and of the infant.
  • H-type histo-blood group antigens In Europe, about 80% of individuals express H-type histo-blood group antigens in a soluble form in biological fluids including breast milk, serum. In about the remaining 20%, the soluble H- type histo-blood group antigens are essentially absent from in biological fluids. These two phenotypes have been designated as “secretors” and “non- secretors” respectively and the soluble H-type histo-blood group antigens are typically referred to as secretor antigens.
  • the basis for the phenotypic difference between the secretor and non-secretor subpopulations stems from genetic polymorphisms resulting in the expression of functional alpha-l,2-fucosyltransferase in case of secretors whereas non-secretors do not express functional alpha- 1,2-fucosyltransferase. Accordingly, soluble H-type histo-blood group antigens are not synthesized and therefore not secreted into biological fluids of non-secretors.
  • the Lewis blood typing system distinguishes the antigens Lewis a and Lewis b (Le a and Le b). These antigens are soluble antigens which may be present in body fluids including human milk.
  • Lewis a-/b- There are three phenotypes: Le(a-/b-); Le(a+/b-); and Le(a-/b+).
  • the presence of fucosyltransferase converts the Lewis a antigen to Lewis b.
  • Individuals with Lewis a antigens are usually non-secretors, and the presence of the Lewis b antigen makes a person a secretor.
  • Lewis negative (Le a-, Le b-) can be either secretors or non-secretors.
  • WO 2009/033011 concerns a diagnostic method for identifying an individual at risk for necrotizing enterocolitis and related disorders by measuring the level of secretor antigens, in particular H-antigens and Lewis antigens, in saliva.
  • Human milk oligosaccharides are considered to protect breast-fed infants from pathogenic bacteria, viruses, toxins, protozoa and fungi by acting as soluble receptor analogues that prevent the interaction of pathogens with epithelial cells in the initial step of infections. Furthermore, such oligosaccharides may act as prebiotics, hence to promote growth of Bifidobacterium bifidum while thereby suppressing growth of undesirable bacteria.
  • WO 98/43494 concerns the analysis of a large number of human milk samples to determine appropriate average levels of nine important milk oligosaccharides and to arrive at the preparation of a synthetic infant formulation containing these oligosaccharides near the naturally occurring levels found in human breast milk.
  • Secreting infants are characterized as having blood group A, B, or AB according to the ABO blood group system and/or having Lewis blood type Le(a+/b-) or Le(a-/b-) according to the Lewis blood typing system.
  • Non-secreting mothers are characterized by having blood group O of the ABO blood group system and/or having Lewis blood type Le(a+/b-) according to the Lewis blood typing system.
  • the present invention thus concerns a method for feeding an infant who has a) blood group A, B, or AB according to the ABO blood group system and/or b) Lewis blood type Le(a+/b-) or Le(a-/b-) according to the Lewis blood typing system, said method comprising administering a nutritional composition comprising 2-fucosylated oligosaccharides.
  • the invention concerns the use of a composition comprising 2- fucosylated oligosaccharides for the preparation of a nutritional composition for feeding an infant, said infant having ) blood group A, B, or AB according to the ABO blood group system and/or b) Lewis blood type Le(a+/b-) or Le(a-/b-) according to the Lewis blood typing system.
  • the nutritional composition may be a complete infant formula as such.
  • the nutritional composition may also be a nutritional supplement or may be a supplemented human milk.
  • nutritional supplement comprises 2-fucosylated oligosaccharides or the human milk is supplemented with a composition comprising 2-fucosylated oligosaccharides. According to the present invention it is especially advantageous to supplement the human milk of a non-secreting mother.
  • the present invention concerns the use o f 2-fucosylated oligosaccharides for the preparation of a nutritional supplement for supplementing human milk for feeding an infant who has a) blood group A, B, or AB according to the ABO blood group system and/or b) Lewis blood type Le(a+/b-) or Le(a-/b-) according to the Lewis blood typing system.
  • the human milk that is supplemented is the human milk of a mother who has a) blood group O according to the ABO blood group system, and/or b) Lewis blood type Le(a+/b-) according to the Lewis blood typing system.
  • the invention also concerns a nutritional supplement comprising 2-fucosylated oligosaccharides for use in supplementing an infant formula or a human milk for feeding an infant, wherein the infant has a) blood group A, B, or AB according to the ABO blood group system and/or b) Lewis blood type Le(a+/b-) or Le(a-/b-) according to the Lewis blood typing system.
  • the nutritional supplement is for supplementing human milk of a mother who has a) blood group O according to the ABO blood group system, and/or b) Lewis blood type Le(a+/b-) according to the Lewis blood typing system.
  • Method for preparing a nutritional composition comprising supplementing milk from a mother that has a) blood group O according to the ABO blood group system, and/or b) Lewis blood type Le(a+/b-) according to the Lewis blood typing system with a composition comprising 2-fucosylated oligosaccharides.
  • the nutritional composition is for an infant that has a) blood group A, B, or AB according to the ABO blood group system and/or b) Lewis blood type Le(a+/b-) or Le(a-/b-) according to the Lewis blood typing system.
  • the blood type is determined using the Lewis blood typing system.
  • the infant has Lewis blood type Le(a+/b-) or Le(a-/b-) according to the Lewis blood typing system.
  • the mother has Lewis blood type Le(a+/b-) according to the Lewis blood typing system.
  • Pr e fer ab ly the 2-fucosylated oligosaccharides comprise alpha-l,2-fucosyl oligosaccharides, preferably 2 ' -fucosyllactose and/or lacto-N-fucopentaose I.
  • 2 ' - Fucosyllactose is also abbreviated as 2 ' -FL and can also be represented by Fuc-a- (l ⁇ 2)Gal- -(l ⁇ 4)-Glc.
  • Lacto-N-fucopentaose I is also abbreviated as LNFP I and can also be represented by Fuc-a-(l ⁇ 2)Gal-p-(l ⁇ 3)-GlcNAc-p-(l ⁇ 3)-Gal-p-(l ⁇ 4)-Glc. Both are commercially available for instance from Sigma- Aldrich. Alternatively, they can be isolated from human milk, for example as described in Andersson & Donald, 1981, J Chromatogr. 211 : 170-1744, or produced by genetically modified microorganisms, for example as described in Albermann et al, 2001, Carbohydrate Res. 334:97-103.
  • the nutritional composition fed to the infant comprises 100 mg to 2 g 2- fucosylated oligosaccharides per 100 ml, more preferably 150 mg to 1.8 g, even more preferably 200 mg to 1.5 g, even more preferably 400 mg to 1 g, even more preferably 500 mg to 1 g 2-fucosylated oligosaccharides per 100 ml.
  • the composition preferably comprises 0.6 wt% to 15 wt% 2-fucosylated oligosaccharides, more preferably 1 wt% to 12 wt%, even more preferably 1.3 wt% to 10 wt%, even more preferably 2.5 wt% to 6.5 wt%, even more preferably 3.3 wt% to 6.5 wt%.
  • a lower amount of 2-fucosylated oligosaccharides will be less effective in preventing from infections by pathogens, whereas a too high amount will result in unnecessary high costs of the product.
  • the nutritional supplement preferably comprises at least 10 wt% 2-fucosylated oligosaccharides based on dry weight of the supplement.
  • the 2-fucosylated oligosaccharides are preferably mixed with an inert carrier or bulking agent, for example maltodextrin.
  • the nutritional supplement comprises 10 wt% to 90 wt% 2-fucosylated oligosaccharides, preferably 15 wt% to 80 wt%, preferably 25 wt% to 75 wt%, preferably 30 wt% to 65 wt%, preferably 40 wt% to 55 wt%.
  • the nutritional supplement is in the form of a powder.
  • such an amount of the powdered nutritional supplement is added to human milk as to arrive at a supplemented human milk that contains 100 mg to 2 g 2-fucosylated oligosaccharides per 100 ml, more preferably 150 mg to 1.8 g, even more preferably 200 mg to 1.5 g, even more preferably 400 mg to 1 g, even more preferably 500 mg to 1 g 2-fucosylated oligosaccharides per 100 ml.
  • the nutritional supplement is packed in a sachet, preferably of a bout 2 g per sachet.
  • 1, 2, 3 or 4 sachets are added per 100 ml breast milk.
  • the nutritional composition preferably comprises non-digestible oligosaccharides (NDO) other than 2-fucosylated oligosaccharides.
  • NDO non-digestible oligosaccharides
  • the NDO other than 2- fucosylated oligosaccharides stimulate the growth of bifidobacteria and/or lactobacilli, more preferably bifidobacteria.
  • An increased content of bifidobacteria and/or lactobacilli stimulate the formation of a healthy intestinal microbiota.
  • the NDO are preferably not or only partially digested in the intestine by the action of acids or digestive enzymes present in the human upper digestive tract, in particular in the small intestine and stomach, and are fermented by the human intestinal microbiota.
  • sucrose, lactose, maltose and the common maltodextrins are considered digestible.
  • the present composition comprises non-digestible oligosaccharides with a DP in the range o f 2 to 250, more preferably 2 to 60.
  • the non-digestible oligosaccharide is preferably at least one, more preferably at least two, preferably at least three selected from the group consisting of fructo-oligosaccharides, galacto- oligosaccharides, xylo-oligosaccharides, arabino-oligosaccharides, arabinogalacto- oligosaccharides, gluco-oligosaccharides, chito-oligosaccharides, glucomanno- oligosaccharides, galactomanno-oligosaccharides, mannan-oligosaccharides, sialic acid comprising oligosaccharides, and uronic acid oligosaccharides.
  • the group of fructo- oligosaccharides includes inulins
  • the group of galacto-oligosaccharides includes transgalacto-oligosaccharides or beta-galacto-oligosaccharides
  • the group of gluco- oligosaccharides includes cyclodextrins, gentio- and nigero-oligosaccharides and non- digestible polydextrose
  • the group of galactomanno-oligosaccharides includes partially hydrolyzed guar gum
  • the group of uronic acid oligosaccharides includes galacturonic acid oligosaccharides and pectin degradation products.
  • the present composition comprises at least one, more preferably at least two, most preferably three selected from the group consisting of fructo- oligosaccharides, beta-galacto-oligosaccharides and uronic acid oligosaccharides. More preferably the composition comprises beta-galacto-oligosaccharides.
  • the composition comprises a mixture of inulin and short chain fructo-oligosaccharides.
  • the composition comprises a mixture of galacto-oligosaccharides and fructo-oligosaccharides selected from the group consisting of short chain fructo-oligosaccharides and inulin, more preferably inulin.
  • a mixture of at least two different non-digestible oligosaccharides advantageously stimulates the beneficial bacteria of the intestinal microbiota to a greater extent.
  • the weight ratio in a mixture of the two different non- digestible oligosaccharides is between 25 and 0.05, more preferably between 20 and 1.
  • Galacto- oligosaccharides preferably beta-galacto-oligosaccharides, are more capable of stimulating bifidobacteria.
  • the present composition comprises galacto- oligosaccharides, preferably beta-galacto-oligosaccharides, with a d e gre e o f polymerization (DP) of 2 to 10 and/or fructo-oligosaccharides with a DP of 2 to 60.
  • DP d e gre e o f polymerization
  • the galacto-oligosaccharides preferably are beta-galacto-oligosaccharides.
  • the present composition comprises beta-galacto- oligosaccharides ([galactose]n-glucose; wherein n is an integer ranging from 2 to 60, i.e. 2, 3, 4, 5, 6, 59 ,60; preferably n is selected from 2, 3, 4, 5, 6, 7, 8, 9, and 10), wherein the galactose units are in majority linked together via a beta linkage.
  • Beta- galacto-oligosaccharides are also referred to as trans-galacto-oligosaccharides (TOS).
  • Beta-galacto-oligosaccharides are for example sold under the trademark Vivinal 1 -TM ⁇ (Borculo Domo Ingredients, Netherlands). Another suitable source is Bi2Munno (Classado).
  • the TOS comprises at least 80 % beta- 1,4 and beta- 1,6 linkages based on total linkages, more preferably at least 90 %.
  • Fructo-oligosaccharide is a NDO comprising a chain of beta- linked fructose units with a DP or average DP of 2 to 250, more preferably 2 to 100, even more preferably 10 to 60.
  • Fructo-oligosaccharide includes inulin, levan and/or a mixed type of polyfructan.
  • An especially preferred fructo-oligosaccharide is inulin.
  • Fructo-oligosaccharide suitable for use in the compositions is also commercially available, e.g. Raftiline®HP (Orafti).
  • the fructo-oligosaccharide has an average DP above 20.
  • Uronic acid oligosaccharides are preferably obtained from pectin degradation products.
  • the present composition preferably comprises a pectin degradation product with a DP of 2 to 100.
  • the pectin degradation product is prepared from apple pectin, beet pectin and/or citrus pectin.
  • the uronic acid oligosaccharide is a galacturonic acid oligosaccharide.
  • the composition comprises FL and one of the group selected from galacto -oligosaccharide and uronic acid oligosaccharide.
  • the composition comprises beta-galacto-oligosaccharide, fructo-oligosaccharide and a uronic acid oligosaccharide. It was found that such a combination acts synergistically with fucosyllactose, in particular 2'-fucosyllactose.
  • the weight ratio beta-galacto-oligosaccharide : fructo- oligosaccharide : uronic acid oligosaccharide is preferably (20 to 2) : 1 : (1 to 20), more preferably (20 to 2) : 1 : (1 to 10), even more preferably (20 to 2) : 1 : (1 to 3), even more preferably (12 to 7) : 1 : (1 to 2). Most preferably the weight ratio is about 9 : 1 : 1.1..
  • the nutritional composition comprises 200 mg to 4 g non-digestible oligosaccharides, including 2-fucosylated oligosaccharides, per 100 ml, more preferably 400 mg to 3.5 g, even more preferably 500 mg to 3 g, even more preferably 800 mg to 2.5 g even more preferably 1 g to 2 g non-digestible oligosaccharides per 100 ml.
  • the composition preferably comprises 1 wt% to 25 wt% non-digestible oligosaccharides including 2-fucosylated oligosaccharides, more preferably 2.5 wt% to 20 wt%, even more preferably 3.3 wt% to 18 wt%, even more preferably 5 wt% to 15 wt%, even more preferably 6.5 wt% to 13 wt%.
  • a lower amount of non-digestible oligosaccharides will be less effective in stimulating the beneficial bacteria in the microbiota, whereas a too high amount will result in side- effects of bloating and abdominal discomfort.
  • the nutritional composition of the present invention is not human milk.
  • the present nutritional composition is preferably enterally administered, more preferably orally.
  • the present nutritional composition is preferably an infant formula.
  • the present nutritional composition can be advantageously applied as a complete nutrition for infants.
  • the present composition preferably comprises a lipid component, protein component and carbohydrate component and is preferably administered in liquid form.
  • the present invention includes dry food, preferably a powder, which is accompanied with instructions as to admix said dry food mixture with a suitable liquid, preferably with water.
  • the present nutritional composition preferably comprises lipid, protein and digestible carbohydrate, wherein the lipid component provides 5 to 50% of the total calories, the protein component provides 5 to 50%> of the total calories, and the digestible carbohydrate component provides 15 to 85% of the total calories.
  • the lipid component provides 20 to 50% of the total calories, the protein component provides 5 to 30% of the total calories, and the digestible carbohydrate component provides 30 to 70% of the total calories.
  • the lipid component provides 35 to 50% of the total calories, the protein component provides 7.5 to 12.5% of the total calories, and the digestible carbohydrate component provides 40 to 55% of the total calories.
  • the total of energy provided by the proteins, peptides and amino acids needs to be taken into account.
  • the nutritional composition preferably comprises at least one lipid selected from the group consisting of animal lipid, excluding human lipids, and vegetable lipids.
  • the present composition comprises a combination of vegetable lipids and at least one oil selected from the group consisting of fish oil, animal oil, algae oil, fungal oil, and bacterial oil.
  • the present composition preferably comprises long chain polyunsaturated fatty acids (LC-PUFA).
  • LC-PUFA are fatty acids or fatty acyl chains with a length of 20 to 24 carbon atoms, preferably 20 or 22 carbon atoms comprising two or more unsaturated bonds.
  • the present composition comprises eicosapentaenoic acid (EPA, n-3), docosahexaenoic acid (DHA , n-3) and/or arachidonic acid (ARA, n-6).
  • the present composition comprises at least 0.1 wt.%, preferably at least 0.25 wt.%, more preferably at least 0.6 wt.%, even more preferably at least 0.75 wt.% LC- PUFA with 20 and 22 carbon atoms based on total lipid content.
  • the content of LC-PUFA particularly the LC-PUFA with 20 and 22 carbon atoms, preferably does not exceed 6 wt%, more preferably does not exceed 3 wt.% of the total lipid content as it is desirable to mimic human milk as closely as possible.
  • the LC- PUFA may be provided as free fatty acids, in triglyceride form, in diglyceride form, in monoglyceride form, in phospholipid form, or as a mixture of one of more of the above.
  • the present composition preferably comprises between 5 and 75 wt.% polyunsaturated fatty acids based on total fat, preferably between 10 and 50 wt.%.
  • the protein in the nutritional composition is preferably selected from the group consisting of non-human animal proteins (preferably milk proteins), vegetable proteins (preferably soy protein and/or rice protein), hydrolysates thereof, free amino acids and mixtures thereof.
  • the nutritional composition preferably contains casein, whey, hydrolyzed casein and/or hydrolyzed whey protein.
  • the protein comprises intact proteins, more preferably intact bovine whey proteins and/or intact bovine casein proteins.
  • the nutritional composition preferably contains digestible carbohydrates selected from the group consisting of sucrose, lactose, glucose, fructose, corn syrup solids, starch and maltodextrins, more preferably lactose.
  • the liquid food does not have an excessive caloric density, however still provides sufficient calories to feed the infant.
  • the liquid food preferably has a caloric density between 0.1 and 2.5 kcal/ml, even more preferably a caloric density of between 0.5 and 1.5 kcal/ml, most preferably between 0.6 and 0.8 kcal ml.
  • the nutritional composition comprises nucleotides and/or nucleosides, more preferably nucleotides.
  • the composition comprises cytidine 5 '- monophospate, uridine 5 '-monophospate, adenosine 5 '-monophospate, guanosine 5 '- monophospate, and/or inosine 5 '-monophospate, more preferably cytidine 5 '- monophospate, uridine 5 '-monophospate, adenosine 5 '-monophospate, guanosine 5 '- monophospate, and inosine 5 '-monophospate.
  • the composition comprises 5 to 100, more preferably 5 to 50 mg, most preferably 10 to 50 mg nucleotides and/or nucleosides per 100 gram dry weight of the composition. Infant
  • the present method is advantageously applied to a human infant of 0-36 months, more preferably to a human infant of 0-18 months, more preferably to a human infant of 0-12 months, even more preferably to a human infant of 0-6 months.
  • a human infant of 0-18 months more preferably to a human infant of 0-12 months
  • 2-fucosylated oligosaccharides as early as possible.
  • Fig. 1 shows the variation of neutral and acidic oligosaccharides within milk groups 1- 3. All data points represent mean values of the corresponding oligosaccharide concentrations at seven times postpartum. However, statistical calculations are based on individual values. Straight lines indicate significant trends (P ⁇ 5%); the dotted trend line indicates not significant variations during time.
  • Fig. 2 shows the variation of al,2-, al,4- and al,3-linked fructose moieties. All data points represent mean values of the corresponding oligosaccharide concentrations at seven times postpartum. However, statistical calculations are based on individual values. Fucal-2Gal: al,2-linked fucosyl moieties as detected in milk groups 1 or 3;
  • Fucal-4GlcNAc al,4-linked fucosyl moieties as detected in milk groups 1 or 2;
  • Fucal-3Glc al,3-fucosyl moieties linked to subterminal glucose as detected in milk groups 1, 2, 3;
  • Fucal-3GlcNAc al,3-fucosyl moieties linked to GlcNAc as detected in milk groups 1, 2, 3;
  • No significant trends (P>5%) were found with Fucal-4GlcNAc: milk groups 1 and 2
  • Fucal-3Glc milk group 3
  • Fuca 1-3 GlcNAc milk groups 1 and 3.
  • Figures 3-9 show tables 1-7 referred to in the examples.
  • Lewis blood groups of the women were determined within 3 days post partum on the day of blood sampling by a haemagglutination tube test. Haemagglutination was examined using corresponding erythrocyte suspensions (3%-5% erythrocytes suspended in 0,9% NaCl ) and monoclonal anti-Le a and anti-Le b antibodies (Immucor, Rodermark, Germany and BAG, Lich, Germany). Incubation was performed at room temperature for 15 min. Due to discrepancies between serologic tests and chromatographic profiles, some heamagglutination tests were repeated 18 - 25 months post partum. The women were not pregnant at that time.
  • Sample preparation including gel permeation chromatographic purification, as well as HPAEC-analyses were performed as already described. Briefly, human milk samples were heated for 30 min at 70 °C. One millilitre of human milk was added with 0,1 ml of an aqueous solution containing the internal standards stachyose and galacturonic acid. The samples were subsequently centrifuged and ultrafiltrated (Millipore Centrifree, 30 kDa cutoff). The protein and lipid reduced samples were fractionated into lactose, neutral oligosaccharides and acidic oligosaccharides by gel permeation chromatography using Toyopearl HW 40 (S ) columns (1,6 x 80 cm TosoHaas, Stuttgart, Germany).
  • S Toyopearl HW 40
  • the carbohydrate fractions were eluted with water (flow rate of 1 ml/min) and monitored by refractive index detection.
  • the lactose fraction was discarded; the neutral and acidic fractions were analysed by HPAEC-PED.
  • the eluents used for analysis of neutral oligosaccharides were 0-20 min, 30 mM NaOH; 20-34 min, 30-100 mM NaOH; 34-48 min, 100 mM NaOH / 0-28 mM NaOAc; 48-55 min, 100 mM NaOH / 28-200 mM NaOAc; 55-60 min, 100 mM NaOH / 200 mM NaOAc.
  • the elution conditions for acidic oligosaccharides were 0-8 min, 100 mM NaOH / 20 mM NaOAc; 8-30 min, 100 mM NaOH / 20-80 mM NaOAc; 30-55 min, 100 mM NaOH / 80-200 mM NaOAc; 55-60 min, 100 mM NaOH / 200 mM NaOAc.
  • Neu5Ac N-acetyl neuraminic acid
  • the data set is two-factorially organized, in three milk groups and seven lactation times, respectively. Besides, the data set is very unbalanced due to different sample numbers.
  • milk group 1 the 109 samples in total are allocated to the times in a range from 10 to 21 samples, whereas in group 2 (28 samples) a lactation time is represented by 3 - 5 samples and in group 3 (17 samples) by 2 - 3 samples. Therefore several methods for analyzing the means of oligosaccharide concentrations were applied.
  • an one-factorial analysis of variance (ANOVA) followed by a Student-Newman-Keuls-test to compare the mean values of lactation times was used.
  • Milk samples of the five nonsecretor women (Lewis blood type Le(a+b-)) lacked 2'-FL, LDFT, LNFP I, LNDFH I, 2'-F-LNH and 2',3'-DF- LNH and could be assigned to the second milk group, because no a 1,2- fucosyloligosaccharides were detected (Table 1).
  • Table 1 In the milk samples of three mothers with Lewis blood type Le(a-b-) al,2- and al,3-fucosyloligosaccharides were found, whereas LNFP II, LNDFH I and LNDFH II with al ,4 fucose residues were missing.
  • the molar concentrations of the core structures detected in samples of all three milk groups, lactose, LNT, LNnT and LNH, are shown in Table 4.
  • Total core structures, including unmodified, fucosylated or sialylated oligosaccharides, are compared to the corresponding not decorated core structures.
  • Lactose that can be interpreted as glucose analogue of type 2 chains, was by far the most abundant core structure exceeding LNT, a type 1 structure, on average by a factor of 34 (Table 4).
  • LNnT, a typical type 2 structure, and LNH were detected in even lower quantities. Lactose was found to be the prevalent form (about 95%) of the core structure lactose.
  • unmodified LNT, LNnT and LNH varied between 17% and 31% in relation to the corresponding total core structures.
  • fucosylated and sialylated sugars are the predominant forms of these three basic components.
  • Table 6 and Figure 2 summarize the variation of fucosylated oligosaccharides during the course of lactation with regard to the three milk groups. Oligosaccharides were summed on a molar basis according to four different linkage types: al,2-fucose linked to terminal galactose (Fucal-2Gal), al,4-fucose linked to subterminal N- acetylglucosamine (Fucal-4GlcNAc), al,3-fucose linked to reducing glucose (Fucal- 3Glc), al,3-fucose linked to subterminal GlcNAc (Fucal-3GlcNAc).
  • Oligosaccharides were summed on a molar basis according to four different linkage types: al,2-fucose linked to terminal galactose (Fucal-2Gal), al,4-fucose linked to subterminal N- acetylglucosamine (Fucal-4
  • the Lewis enzyme isolated from human milk as well as a soluble form of the recombinant FucT III have been reported to link fucose also to the 3-0 position of the reducing glucose of human milk oligosaccharides in reasonable amounts. Therefore we assume that the major portion of these a 1, 3 -fucosyloligo saccharides are the product of the Lewis enzyme, too. A smaller portion should be due to further fucosyltransferases.
  • the especially high amounts of the Fucal-3Glc motif in milk group two, that are caused by high quantities of 3-FL and LNDFH II, can only be partially explained with an increased activity of the Lewis enzyme.
  • a so-called ST6GlcNAc could transfer sialic acid moieties to subterminal GlcNAc yielding LSTb as well as DSLNT, an oligosaccharide exhibiting both a2,6-linked and a2,3-linked neuraminic acid.
  • Human milk oligosaccharides especially those compounds containing lacto-N-biose (type 1 structure) or GlcNAc, are thought to promote growth of a favorable gut flora in newborns.
  • the total core structures LNT and LNH exhibiting lacto-N-biose units and representing the major GlcNAc-containing oligosaccharides in human milk, attain maximum levels after approximately 1 week postpartum and decline thereafter almost twofold until three months postpartum. Therefore it can be concluded that newborns obtain the best protection from human milk oligosaccharides during the first few weeks of lactation.
  • secretor women corresponding to milk groups one and three significantly produced higher amounts of these core structures than nonsecretors of milk group two. It remains to be investigated whether the gut flora of nonsecretor mothers differs analogously with a lower occurrence of protective species, like Bifidobacteria, Lactobacilli.
  • Infant formula comprising per 100 ml (66 kcal):
  • non-digestible oligosaccharides of which 200 mg 2'-fucosyllactose, 720 mg beta- galacto-oligosaccharides, and 80 mg fructo-oligosaccharides
  • choline choline, myo-inositol, taurine, minerals, trace elements, and vitamins as known in the art
  • Nutritional supplement for supplementing the milk of a mother who has blood group O and/or Lewis blood type Le(a+/b-) packed in a sachet with the following composition: A:
  • Advised dosage is 1 to 4 sachets of supplement A per 100 ml breast milk.
  • Advised dosage is 1 or2 sachets of supplement A per 100 ml breast milk.
PCT/NL2010/050240 2010-04-27 2010-04-27 Use of human milk oligosaccharides in infant nutrition WO2011136637A1 (en)

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PCT/NL2010/050240 WO2011136637A1 (en) 2010-04-27 2010-04-27 Use of human milk oligosaccharides in infant nutrition
CN2011800317016A CN102946742A (zh) 2010-04-27 2011-04-27 人乳寡糖在婴儿营养物中的用途
PL11720600T PL2563166T3 (pl) 2010-04-27 2011-04-27 Stosowanie oligosacharydów mleka ludzkiego w żywieniu niemowląt
EP14168113.0A EP2767173A1 (de) 2010-04-27 2011-04-27 Verwendung von Muttermilch-Oligosaccharisden in Kindernahrung
CN201610818346.1A CN106509916A (zh) 2010-04-27 2011-04-27 人乳寡糖在婴儿营养物中的用途
ES11720600.3T ES2490269T3 (es) 2010-04-27 2011-04-27 Uso de oligosacáridos de leche humana en la nutrición de bebés
PCT/NL2011/050286 WO2011136648A1 (en) 2010-04-27 2011-04-27 Use of human milk oligosaccharides in infant nutrition
EP11720600.3A EP2563166B1 (de) 2010-04-27 2011-04-27 Verwendung von muttermilch-oligosacchariden in kindernahrung

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WO2020127161A1 (en) * 2018-12-20 2020-06-25 Société des Produits Nestlé S.A. Human milk fortifier composition
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WO2018069534A1 (en) * 2016-10-14 2018-04-19 Mead Johnson Nutrition Company Personalized pediatric nutrition products comprising human milk oligosaccharides
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WO2020127161A1 (en) * 2018-12-20 2020-06-25 Société des Produits Nestlé S.A. Human milk fortifier composition
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RU2805191C2 (ru) * 2018-12-20 2023-10-12 Сосьете Де Продюи Нестле С.А. Композиция обогатителя грудного молока

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