WO2011136636A1 - Utilisation de 6'-sialyl lactose dans la nutrition des nourrissons - Google Patents
Utilisation de 6'-sialyl lactose dans la nutrition des nourrissons Download PDFInfo
- Publication number
- WO2011136636A1 WO2011136636A1 PCT/NL2010/050239 NL2010050239W WO2011136636A1 WO 2011136636 A1 WO2011136636 A1 WO 2011136636A1 NL 2010050239 W NL2010050239 W NL 2010050239W WO 2011136636 A1 WO2011136636 A1 WO 2011136636A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- oligosaccharides
- nutritional composition
- oligosaccharide
- milk
- infant
- Prior art date
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- A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
- A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
- A23L33/22—Comminuted fibrous parts of plants, e.g. bagasse or pulp
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, 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
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention is in the field of infant nutrition.
- Sialyl oligosaccharides are present in milk of mammals and have been found to be of biological significance. They are known to possess prebiotic activity, and bifidogenic effects have been described. Also sialyl oligosaccharides are known to have an anti- adhesive effect, thereby playing an important role in inhibiting or preventing intestinal infections by pathogens and/or toxins. It is known that the concentration of the sialyl oligosaccharides in for instance cow's milk is very low whereas in human milk concentrations are considerably higher. Because most infant formulas are manufactured with bovine milk components, it follows that formula-fed infants are subject to reduced sialyl oligosaccharide intake compared to breast-fed infants. Prominent members of the sialyl oligosaccharides are 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL).
- WO 2009/059996 concerns nutritional compositions for use in preventing secondary infections following a viral infection, comprising sialylated oligosaccharides and in particular 3'-SL and 6'-SL.
- the present inventors surprisingly found that in order to match the quantities of 6'- sialyllactose (6'-SL) that are actually present in human milk, a much higher amount of 6'-SL needs to be formulated in infant formula than nowadays is done.
- the present inventors also found that the relative amount of 3 '-sialyllactose (3'- SL) to 6 '-SL as actually is present in human milk is shifted to a relatively lower contribution of 3 '-SL compared to the relative amounts or ratio of the two as is nowadays applied in infant formula.
- the present inventors found that in order to resemble human milk as close as possible and to preferably arrive at a more optimal prebiotic activity, and bifidogenic effect and/or anti-adhesive effect of sialyl oligosaccharides, preferably of 6'-SL and 3 '-SL, infant formula need to be formulated differently than currently is done, in particular with respect to the amounts of sialyl oligosaccharides, preferably of 6'-SL and 3 '-SL. In doing so, an improved intestinal healthy will be achieved and preferably an improvement in inhibiting or preventing intestinal infections by pathogens and/or toxins is achieved.
- the present invention thus concerns a method of providing nutrition to an infant, said method comprising administering a composition comprising at least 1 g/1 6 '- sialyllactose (6'-SL) and wherein the weight ratio 6'-SL : 3'-SL is higher than 2.
- the present invention can also be worded as concerning the use of a composition comprising 6'-sialyllactose (6'-SL) in the manufacture of a nutritional composition for providing nutrition to an infant, said nutritional composition comprising at least 1 g/1 6'-SL and wherein the weight ratio 6'-SL : 3'-SL is higher than 2.
- 6'-SL 6'-sialyllactose
- the invention can also be worded as a composition comprising at least 1 g/1 6'- sialyllactose (6'-SL) and wherein the weight ratio 6'-SL : 3'-SL is higher than 2 for use in providing nutrition to an infant.
- the invention also concerns a nutritional composition, preferably an infant formula, that comprises lipid that provides 35 to 50% of the total calories, protein that provides 7.5 to 12.5% of the total calories, and digestible carbohydrate that provides 40 to 55% of the total calories and further comprising at least 1 g/1 6'-SL and wherein the ratio 6'- SL : 3'-SL is higher than 2.
- the present nutritional composition preferably comprises at least 1 g/1 6'-SL, more preferably at least 1.1 g/1. This concentration is more pronounced of human milk commonly applied in infant milk formula and is therefore to be preferred.
- the present nutritional composition preferably comprises less than 3 g/1 6'-SL, more preferably less than 2.5 g/1, more preferably less than 2 g/1, more preferably less than 1.5 g/1 6'-SL, more preferably between 1.1 and 1.5 g/1, more preferably between 1.1 and 1.4 g/1, more preferably between 1.2 and 1.4 g/1.
- the present nutritional composition further preferably comprises 3 '-SL and the weight ratio 6'-SL : 3 '-SL is higher than 2.
- the weight ratio 6'-SL : 3 '-SL is higher than 2.5, preferably higher than 3, preferably higher than 3.5.
- the weight ratio 6'-SL : 3 '-SL is lower than 6.
- the weight ratio 6'-SL : 3 '-SL is between 2.5 and 5.5, preferably between 3 and 5.
- the present composition in one embodiment comprises at least 0.7 wt% 6'-SL based on total dry weight of the composition, preferably between 0.7 wt% and 2.1 wt%, preferably between 0.8 and 1.5 wt%, preferably between 0.85 and 1.0 wt% based on total dry weight of the composition.
- the present nutritional composition can be prepared by a process for manufacturing an infant milk formula comprising a) adding non digestible oligosaccharides derived from cow's milk, b) adding 6'-SL.
- 6'-SL is commercially available and can be purchased from Sigma-Aldrich. Also 6'-SL can be synthesized by metabolically engineered E. coli expressing a multifunctional sialyltransferase from the Photobacterium sp. JT-ISH-224 as described by Drouillard et al in a submission to Carbohydrate Research which at present is in press. The corrected proof is available at
- Non-digestible oligosaccharides other than 6 '-sialyllacotse and 3 '-sialyllactose The nutritional composition preferably comprises non-digestible oligosaccharides (NDO) other than 6'-SL and 3 '-SL.
- NDO non-digestible oligosaccharides
- the NDO other than 26'-SL and 3 '-SL 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.
- 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 of 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 degree of polymerization (DP) of 2 to 10 and/or fructo-oligosaccharides with a DP of 2 to 60.
- DP degree of 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 6'-SL and 3 '-SL.
- 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 100 mg to 4 g non-digestible oligosaccharides, including 6'-SL and 3 '-SL, per 100 ml, more preferably 500 mg to 3 g, even more preferably 800 mg to 2 g non-digestible oligosaccharides per 100 ml.
- the composition preferably comprises 0.5 wt% to 25 wt% non- digestible oligosaccharides including 6'-SL and 3 '-SL, more preferably 1 wt% to 15 wt%, even more preferably 5 wt% to 10 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).
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- ARA arachidonic acid
- 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, pea protein and/or rice protein), hydro lysates thereof, free amino acids and mixtures thereof.
- the nutritional composition preferably contains casein, whey, hydro lyzed 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.
- 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.
- the infant formula is advantageous to formulate with the amounts of 6 '-SL and ratio of 6 '-SL to 3 '-SL according to the present invention.
- a Stage 1 and a Stage 2 infant formula are formulated with the amounts of 6'-SL and ratio of 6 '-SL to 3 '-SL according to the present invention.
- a Stage 1 infant formula is formulated with the amounts of 6'-SL and ratio of 6 '-SL to 3 '-SL according to the present invention.
- a Stage 1 formula is for providing nutrition to an infant of preferably less than 6 months, preferably for providing nutrition to an infant of preferably less than 4 months.
- 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 (Thurl et al. 1998 Milchwissenschaft 53: 127-129). The women were not pregnant at that time.
- 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).
- 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 elution conditions for acidic oligosaccharides were 0-8 min, 100 niM NaOH / 20 niM NaOAc; 8-30 min, 100 niM NaOH / 20-80 niM NaOAc; 30-55 min, 100 niM NaOH / 80-200 niM NaOAc; 55-60 min, 100 mM NaOH / 200 mM NaOAc.
- Neu5Ac N-acetyl neuraminic acid
- acidic oligosaccharides were quantified along with acidic oligosaccharides.
- Neu5Ac concentrations were relatively constant (average concentration of 0,019 g/L in secretor mothers with Lewis blood group Le(a-b+)).
- the amounts of free NeuAc were of the same magnitude as already reported and correspond to approximately 2% and 4% of oligosaccharide bound NeuAc at the beginning of lactation and after three months, respectively. Therefore significant degradation of acidic oligosaccharides due to the action of sialidases or to heat treatment could be excluded.
- core Lac Lac + 3-FL + 2 ' - FL + LDFT + 3 -SL + 6 -SL;
- core LNT LNT + LNFP I + LNFP 11+ LNDFH I + LNDFH II + LSTa + LSTb + DSLNT;
- core LNnT LNnT + LNFP III + LSTc;
- core LNH LNH + 2 -F-LNH + 3 -F-LNH + 2 ,3 '-DF-LNH;
- Fucal-2Gal 2 -FL + LDFT + LNFP I + LNDFH I + 2 -F-LNH + 2 ,3 '-DF-LNH;
- Fucal-4GlcNAc LNFP II + LNDFH
- 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 secretor mothers with Lewis blood group Le(a-b+) the 109 samples in total are allocated to the times in a range from 10 to 21 samples, whereas in group 2 (non-secretor mothers with Lewis blood group Le(a+b-); 28 samples) a lactation time is represented by 3 - 5 samples and in group 3 (secretor mothers with Lewis blood group Le(a-b-); 17 samples) by 2 - 3 samples. Therefore several methods for analyzing the means of oligosaccharide concentrations were applied.
- 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.
- Infant formula comprising per 100 ml (13.9 dry weight):
- non-digestible oligosaccharides of which 120 mg 6'-SL, 30 mg 3'-SL, 80 mg 2'- fucosyllactose, 720 mg b eta-galacto-oligosaccharides, and 80 mg fructo- oligo saccharides
- choline choline, myo-inositol, taurine, minerals, trace elements, and vitamins as known in the art.
Abstract
La présente invention concerne une composition nutritionnelle pour apporter une nutrition à des nourrissons, où des quantités absolues adaptées de 6'-SL et des quantités relatives de 6'-SL à 3'-SL sont appliquées. Le rapport de 6'-SL à 3'-SL est supérieur à deux, de préférence entre 2,5 et 5,5. La quantité de 6'-SL est d'au moins 1 g/l, de préférence entre 1 et 3 g/l.
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PCT/NL2010/050239 WO2011136636A1 (fr) | 2010-04-27 | 2010-04-27 | Utilisation de 6'-sialyl lactose dans la nutrition des nourrissons |
EP11720599A EP2563165A1 (fr) | 2010-04-27 | 2011-04-27 | Utilisation de 6'-sialyl-lactose dans la nutrition d'un nourrisson et d'un petit enfant |
PCT/NL2011/050285 WO2011136647A1 (fr) | 2010-04-27 | 2011-04-27 | Utilisation de 6'-sialyl-lactose dans la nutrition d'un nourrisson et d'un petit enfant |
CN2011800210644A CN102858191A (zh) | 2010-04-27 | 2011-04-27 | 6’-唾液酸化乳糖在婴儿和幼儿营养物中的用途 |
CN201610421321.8A CN106072654A (zh) | 2010-04-27 | 2011-04-27 | 6’‑唾液酸化乳糖在婴儿和幼儿营养物中的用途 |
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