WO2017043962A1 - Procédé de stimulation de la santé du microbiote après une naissance non naturelle - Google Patents

Procédé de stimulation de la santé du microbiote après une naissance non naturelle Download PDF

Info

Publication number
WO2017043962A1
WO2017043962A1 PCT/NL2015/050632 NL2015050632W WO2017043962A1 WO 2017043962 A1 WO2017043962 A1 WO 2017043962A1 NL 2015050632 W NL2015050632 W NL 2015050632W WO 2017043962 A1 WO2017043962 A1 WO 2017043962A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
birth
section
bifidobacterium
oligosaccharide
Prior art date
Application number
PCT/NL2015/050632
Other languages
English (en)
Original Assignee
N.V. Nutricia
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by N.V. Nutricia filed Critical N.V. Nutricia
Priority to PCT/NL2015/050632 priority Critical patent/WO2017043962A1/fr
Publication of WO2017043962A1 publication Critical patent/WO2017043962A1/fr

Links

Classifications

    • 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
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • 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
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • 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
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis

Definitions

  • the present invention pertains to methods for improving or stimulating the healthy gut microbiota and/or reducing health risks and/or prevention of disorders in infants delivered via caesarean section (C-section).
  • Infants delivered via C-section have an intestinal microbiota which is different from the intestinal microbiota of infants born via the vaginal route. This is once more confirmed further below in Figure 1 in the experimental part.
  • infants born via C- section have a reduced rate of intestinal colonisation by Bifidobacteria and have a less diverse Bifidobacterium intestinal microbiota with regards to species than infants born via the vaginal route, particularly lacking Bifidobacterium breve, Bifidobacterium longum longum subsp. longum. Bifidobacterium infantis and Bifidobacterium bifidum.
  • the intestinal microbiota of infants delivered via C-section have a high content of (undesirable) Enter ob acted aceae such as Klebsiella, and Escherichia coli, from birth.
  • Figures 2 and 3 show that it is possible to improve the bifidobacteria microbiota population and achieve bifidobacteria microbiota levels resembling those observed from the reference group of infants (being vaginally delivered) when the C-section infant is provided with the probiotic species early after birth, significantly improving and accellerating Bifidobacterium microbiota population within 3 days, substantially restoring levels within 5 days, and restoring levels to those of a healthy normal delivery breast-fed infant within to weeks.
  • the inventors also found it may be advantageous to administer the probiotic species to the infant in small volume dosages, e.g. by 'inoculating' the infant.
  • a booster form seems most suited, particularly considering the best timing of the intervention.
  • the inventors have found a method for (a) improving or stimulating the health of gut microbiota and/or (b) reducing health risks and/or (c) prevention of disorders in infants delivered via C-section, said method involving providing an infant delivered via C-section with a composition comprising a therapeutically effective amount of at least one probiotic Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp.
  • the composition is administered to the infant delivered via C- section starting at least in the first sixteen weeks after birth, preferably at least within twelve weeks after birth, even more preferably at least within eight weeks after birth, most preferably at least within four weeks after birth.
  • the composition is administered to the infant delivered via C-section started at least in the first two weeks after birth, preferably within the first week after birth, more preferably at least within 5 days after birth, even more preferably at least within 3 days after birth, most preferably at least within 2 days after birth.
  • the consequences of improving the gastrointestinal Bifidobacterium population in terms of numbers and diversity of species according to the invention are a reduced risk of occurrence or development of allergy, preferably food allergy, eczema (e.g. atopic dermatitis), asthma, allergic rhinitis and/or allergic conjunctivitis in infants delivered by C-section. Improvement of the gastrointestinal Bifidobacterium population in terms of numbers and diversity of species may also result in a reduced risk of infections, including gastrointestinal infections, and reducing the occurrence and/or severity of infections including gastrointestinal infections.
  • Figure 1 shows a comparison of the reference group and the control group in terms of total Bifidobacteria levels over the time period from day 3-5 until week 22, demonstrating that C-section infants (without any supplemented intervention) experience delayed colonisation of bifidobacteria compared to vaginally delivered and breast-fed infants.
  • Figure 2 shows the same graph from Figure 1 with the addition of the results from the prebiotic group and the synbiotic group. In these results, it can be observed that levels of bifidobacteria in the synbiotic group were achieved that resemble those observed from the reference group of infants.
  • Figure 3 shows the percentage of bifidobacteria in each group relative to total bacteria at day 3-5, demonstrating that the effect of the synbiotic group generally described in Figure 2 could be observed from very early days of life.
  • the invention pertains to infants born via caesarean section.
  • a caesarean section (C- section) is a surgical procedure where an infant is delivered through an incision made in the mother's abdominal wall, and then through the wall of the uterus.
  • the infant delivered via C-section may be either term or preterm human infant, where a "preterm infant” is a human infant born before 37 weeks of gestation and a "term infant” is a human born at 37 weeks or later of gestation.
  • the invention particularly pertains to a method for (a) improving or stimulating a healthy gut microbiota and/or (b) reducing health risks and/or (c) prevention of disorders in infants delivered via caesarean section (C-section), said method involving providing an infant delivered via C-section with a composition comprising a therapeutically effective amount of at least one probiotic Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp.
  • the composition is administered to the infant delivered via C-section starting at least in the first sixteen weeks after birth or any of the preferred time windows described herein.
  • the health risks and disorders according to embodiments (b) and (c) are preferably understood being risks and disorders associated with the impaired gut microbiota, particularly the lack of bifidobacteria microbiota that a C-section delivery infant experiences.
  • the invention also pertains to the use of a composition for the manufacture of a medicament for (a) improving or stimulating a healthy gut microbiota and/or (b) reducing health risks and/or (c) prevention of disorders in infants delivered via caesarean section (C-section), wherein said composition comprises a therapeutically effective amount of at least one probiotic Bifidobacterium species as described herein, and wherein the composition is administered to the infant delivered via C-section starting at least in the first sixteen weeks after birth or any of the preferred time windows described herein.
  • the invention also pertains to a composition for use in (a) improving or stimulating a healthy gut microbiota and/or (b) reducing health risks and/or (c) prevention of disorders in infants delivered via caesarean section (C-section), wherein said composition comprises a therapeutically effective amount of at least one probiotic Bifidobacterium species as described herein, and wherein the composition is administered to the infant delivered via C-section starting at least in the first sixteen weeks after birth or any of the preferred time windows described herein.
  • composition further comprises a therapeutically effective amount of at least one non- digestible prebiotic oligosaccharide as described herein.
  • the composition according to the invention comprises a probiotic Bifidobacterium species.
  • probiotic refers to a strain of bacteria which is perceived as probiotic bringing a health benefit to the targeted infants delivered via C-section.
  • Probiotic bifidobacteria are known in the art. It should be noted that it is preferably neither the object nor the effect of the treatment of the invention to promote colonisation by the species of probiotic that is administered but rather to promote colonisation also with other lactic acid producing bacteria, preferably bifidobacteria species so as to achieve an early bifidogenic intestinal microbiota comparable with that found in healthy, breast-fed, vaginally-delivered infants.
  • the improvement or stimulation of a healthy gut microbiota concerns the promotion of the bifidobacteria! colonization of gut of C-section infants, preferably the colonization of at least one Bifidobacterium species other than the one(s) present in the composition according to the invention is promoted.
  • the composition according to the invention comprises B. breve (preferably the sole added probiotic) and the improvement or stimulation of a healthy gut microbiota concerns the promotion of the intestinal colonization of at least one, preferably at least two Bifidobacterium species other than B. breve.
  • the present composition preferably comprises at least one Bifidobacterium selected from the group consisting of B. breve, B. longum subsp. longum, B. longum subsp. infantis, B. bifidum and B. catenulatum, even more preferably at least one Bifidobacterium selected from the group consisting of B. breve and B. longum subsp. longum, most preferably at least B. breve.
  • the composition comprises at least two different Bifidobacterium species, preferably including at least one, more preferably two of the above list, more preferably B. breve and B. longum subsp. longum.
  • the present composition comprises at least three, most preferably at least four different Bifidobacterium species.
  • the composition comprises a maximum of one or two Bifidobacterium species. The above-mentioned combinations commonly aim to increase the diversity and/or the quantity of microorganisms in the intestine of the C-section delivered infant.
  • the probiotic species in the composition consists of one or two, preferably one of the above Bifidobacterium species, and the probiotics in the composition preferably consists of B. breve and B. longum subsp. longum, most preferably consists of B. breve.
  • the present composition further comprises a Lactobacillus selected from the group consisting of L. casei, L. reuteri, L paracasei, L. rhamnosus, L. acidophilus, L. johnsonii, L. lactis, L. salivarius, L. crispatus, L. gasseri, L. zeae, L. fermentum and L. plantarum, more preferably L. casei, L. paracasei, L. rhamnosus, L. johnsonii, L. acidophilus, L. fermentum and most preferably L. paracasei.
  • the probiotic(s) is(are) present in the composition in a therapeutically effective amount or "amount effective for treating" in the context of the invention.
  • the probiotic is included in the present composition in an amount of 10 2 - 10 13 cfu per g dry weight of the composition, suitably 10 5 - 10 12 cfu/g, most suitably 10 7 - 10 10 cfu/g.
  • the aforementioned content of probiotics is especially suitable in case the composition according to the invention is a complete nutrition, in particular an infant formula.
  • the composition according to the invention is in the form of a supplement to be added to a nutritional product
  • the content of the probiotics therein is preferably such that after admixing with the nutritional product, the final product that is to be administered comprises prebiotics in the aforementioned amounts.
  • the supplement according to the invention may contain probiotics in an amount of 10 4 to 10 16 cfu/g,
  • Non-digestible prebiotic oligosaccharides suitably 10 to 10 cfu/g, more suitably 10 to 10 cfu/g, based on dry weight of the supplement.
  • the present composition comprises at least one non-digestible prebiotic oligosaccharide.
  • oligosaccharide refers to saccharides with an average degree of polymerization (DP) of 2 to 250, preferably an average DP 2 to 100, more preferably 2 to 60.
  • the term "prebiotic” refers to one or more non- digestible oligosaccharides.
  • the non-digestible oligosaccharide is water-soluble (according to the method disclosed in L. Prosky et al, J. Assoc. Anal. Chem 71 : 1017-1023, 1988).
  • Non-digestible oligosaccharides are not digested in the intestine by the action of digestive enzymes present in the upper digestive tract (small intestine and stomach) of the C-section infant but instead are fermented by the intestinal microbiota of said infant, thus conferring benefits upon the host wellbeing and health.
  • the growth of at least bifidobacteria and preferably also Lactobacilli is stimulated.
  • An increased content of bifidobacteria and/or lactobacilli stimulate the formation of a healthy intestinal microbiota.
  • Suitable non-digestible oligosaccharides are selected from the group consisting of fructo-oligosaccharide, non-digestible dextrin, galacto-oligosaccharide, xylo- oligosaccharide, arabino-oligosaccharide, arabinogalactooligosaccharide, gluco- oligosaccharide, glucomannooligosaccharide, galactomanno-oligosaccharide, mannanoligosaccharide, chito-oligosaccharide, uronic acid oligosaccharide, sialyl- oligosaccharide and fuco-oligosaccharide.
  • the non-digestible oligosaccharides comprise those obtainable from human milk.
  • the present non-digestible oligosaccharide is preferably selected from the group consisting of galacto-oligosaccharides and fructo-oligosaccharides (including fructo- polysaccharides such as inulin). Preferably at least 50 wt.% of the present non- digestible oligosaccharides have an average degree of polymerisation of 2 to 60.
  • the non-digestible oligosaccharide comprises galacto-oligosaccharides, in particular ⁇ -galacto-oligosaccharides.
  • the galacto-oligosaccharides are preferably [galactose] n -glucose; wherein n is an integer between 1 and 60, i.e.
  • n 2, 3,4,5, 6,...., 59, 60; preferably n is 2, 3, 4, 5, 6, 7, 8, 9 and/or 10, a good example being tram'-galacto- oligosaccharides.
  • the galacto-oligosaccharides preferably comprise saccharides with an average DP of 2 to 10 (scGOS).
  • (Trans)galactooligosaccharide is for example available under the trade name Vivinal®GOS (Borculo Domo Ingredients, Zwolle, Netherlands), Bimuno (Clasado), Cup-oligo (Nissin Sugar) and 01igomate55 (Yakult).
  • Fructo-oligosaccharides may be inulin hydrolysate products having an average DP within the aforementioned (sub-)ranges.
  • Such fructo-oligosaccharide products are for instance commercially available as short-chain fructo-oligosaccharide (scFOS), e.g. the product sold under the trade mark Beneo® P95 or Raftilose P95 (Orafti).
  • scFOS short-chain fructo-oligosaccharide
  • Beneo® P95 or Raftilose P95 (Orafti) A particular type of long-chain fructo-oligosaccharide (lcFOS) is inulin, such as Raftilin HP.
  • the present composition comprises at least galacto-oligosaccharides and fructooligosaccharides and/or fructopolysaccharides, preferably scGOS and lcFOS, suitably in a weight ratio 5 : 1 - 20: 1, even more suitably 7: 1 - 15: 1, even more suitably 8: 1 - 10: 1, most suitably about 9: 1.
  • the prebiotics are present in therapeutically effective or prebiotic amount.
  • the present composition suitably comprises 0.05 to 20 wt% of said non-digestible oligosaccharides, more suitably 0.5 to 15 wt%, even more suitably 1 to 10 wt%, most suitably 2 to 10 wt%, based on dry weight of the present composition.
  • the aforementioned content of prebiotics is especially suitable in case the composition according to the invention is a complete nutrition, in particular an infant formula.
  • the composition according to the invention is in the form of a supplement to be added to a nutritional product
  • the content of the prebiotics therein is preferably such that after admixing with the nutritional product, the final product that is to be administered comprises prebiotics in the aforementioned amounts.
  • a supplement according to the invention may contain prebiotics in a amounts of 0.5 to 80 wt%, suitably 1 to 50 wt%, more suitably 5 to 30 wt%, based on dry weight of the supplement.
  • composition may further comprise long chain polyunsaturated fatty acids (LC- PUFA).
  • LC-PUFA are fatty acids wherein the acyl chain has a length of 20 to 24 carbon atoms (preferably 20 or 22 carbon atoms) and wherein the acyl chain comprises at least two unsaturated bonds between said carbon atoms in the acyl chain.
  • the present composition comprises at least one LC-PUFA selected from the group consisting of eicosapentaenoic acid (EPA, 20:5 n3), docosahexaenoic acid (DHA, 22:6 n3), arachidonic acid (ARA, 20:4 n6) and docosapentaenoic acid (DP A, 22:5 n3), comprising at least DHA.
  • LC-PUFA further have anti-inflammatory effects and promote the adhesion of lactic acid producing bacteria to mucosal surfaces, thereby stimulating the development of a healthy microbiota, which are further advantages for use in C-section delivered infants.
  • 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 at least one of ARA and DHA in phospholipid form.
  • composition is enterally administered, and the term "enteral” is intended to refer to the delivery directly into the gastrointestinal tract of the infant (e.g., orally or via a tube, catheter or stoma), but it also encompasses rectal or anal administration.
  • the present composition may be in any form known in the art, such as in solid form, in semi-solid form or in liquid form.
  • the composition is a nutritional composition or a nutritional supplement, preferably in the form of a powder, capsule or tablet.
  • the composition is not a human milk composition.
  • the composition comprises the probiotic in freeze-dried form, which is especially suitable when the composition is in powder, capsule or tablet form.
  • the present composition when in powder, capsule or tablet form, especially when in powder form, is contained within a container, preferably a stick or stickpack or a sachet.
  • the composition of the invention is in the form of complete nutrition.
  • the composition is intended for oral administration.
  • the composition may comprise an infant formula, preferably in powder form suited to be reconstituted with water.
  • the composition according to the invention is an infant formula.
  • An infant formula for use according to the present invention may contain a protein source in an amount of not more than 2.0 g/lOOkcal, preferably 1.8 to 2.0 g/lOOkcal.
  • the protein preferably provides 5 to 15% of the total calories.
  • the composition comprises protein that provides 6 to 12% of the total calories. More preferably protein is present in the infant formula below 9% based on calories.
  • the source of the protein should be selected in such a way that the minimum requirements for essential amino acid content are met and satisfactory growth is ensured.
  • protein sources based on cow's milk proteins such as whey, casein and mixtures thereof and proteins based on soy, potato or pea are preferred.
  • the infant formula comprises casein and whey protein.
  • the protein source is preferably based on acid whey or sweet whey, whey protein isolate or mixtures thereof and may include alpha-lactalbumin and alpha-lactoglobulin. More preferably, the protein source is based on acid whey or sweet whey from which caseino-glyco- macropeptide (CGMP) has been removed.
  • CGMP caseino-glyco- macropeptide
  • the infant formula comprises casein, preferably it comprises at least 3 wt.% casein based on dry weight.
  • the casein is intact and/or non-hydrolyzed.
  • protein includes peptides and free amino acids.
  • the protein source may be based on acid whey or sweet whey or mixtures thereof and may include alpha-lactalbumin and beta-lactoglobulin in whatever proportions are desired.
  • the proteins may be intact or hydrolysed or a mixture of intact and hydrolysed proteins.
  • the infant formula may contain a carbohydrate source. Any carbohydrate source conventionally found in infant formulae such as lactose, saccharose, maltodextrin, starch and mixtures thereof may be used although the preferred source of carbohydrates is lactose.
  • the carbohydrate sources contribute between 35 and 65% of the total energy of the formula.
  • the infant formula may also contain a source of lipids.
  • the lipid source may be any lipid or fat which is suitable for use in infant formulas.
  • the infant formula contains at least one, suitably at least two lipid sources selected from the group consisting of rape seed oil (such as colza oil, low erucic acid rape seed oil and canola oil), high oleic sunflower oil, high oleic safflower oil, olive oil, marine oils, microbial oils, coconut oil, palm kernel oil and milk fat.
  • the lipid component of the infant formula suitably provides 2.9 to 6.0 g, more suitably 4 to 6 g per 100 kcal of the composition.
  • the infant formula When in liquid form, the infant formula suitably comprises 2.1 to 6.5 g lipid per 100 ml, more suitably 3.0 to 4.0 g per 100 ml. Based on dry weight the infant formula suitably comprises 12.5 to 40 wt% lipid, more suitably 19 to 30 wt%.
  • the fat source preferably has a ratio of n-6 to n-3 fatty acids of about 5: 1 to about 15: 1; for example about 8: 1 to about 10: 1.
  • the infant formula may also contain all vitamins and minerals understood to be essential in the daily diet and in nutritionally significant amounts. Minimum requirements have been established for certain vitamins and minerals.
  • Examples of minerals, vitamins and other nutrients optionally present in the infant formula include vitamin A, vitamin B l, vitamin B2, vitamin B6, vitamin B12, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorous, iodine, iron, magnesium, copper, zinc, manganese, chloride, potassium, sodium, selenium, chromium, molybdenum, taurine, and L-carnitine. Minerals are usually added in salt form.
  • the infant formula may optionally contain other substances which may have a beneficial effect such as lactoferrin, nucleotides, nucleosides, and the like.
  • the composition of the invention is not in the form of complete nutrition.
  • the composition of the invention may be intended to be administered to the infant directly and in addition to breast-milk or infant formula ingested by the infant.
  • Such compositions are typically of small size, e.g. 0.5 - 5 ml or 0.5 - 5 g, and may be referred to as supplement or fortifier.
  • the invention thus pertains to a method for the manufacture of a nutritional product for infants born via caesarean section comprising admixing: (i) human breast milk, infant formula or a mixture thereof; and (ii) the composition (e.g. supplement or fortifier) according to the invention.
  • the invention concerns a method for providing nutrition to an infant, said method comprising the admixing of (i) and (ii) to manufacture a nutritional product as defined above and administering the nutritional product to an infant born via caesarean section, preferably in the aforementioned short time frames after birth.
  • the 'small volume' compositions may also be administered to the infant, e.g. by 'inoculating' the infant, preferably with a syringe, pipette or tube, thus especially useful for C-section infants in hospital settings.
  • the composition is preferably administered in liquid form having a volume between 0.5 to 5 ml.
  • the compositions may be provided in the form of unit dose form, which refers to individual single-use packages.
  • the composition may be present in a container containing one single or more unit dose(s).
  • the composition of the invention is intended to be added to another product before ingestion by the infant.
  • the present composition is accompanied with instructions to add the composition to a nutritional product before ingestion.
  • the nutritional product to which the present composition is to be added may be any suitable nutritional product for C-section infants, such as breast-milk or infant formula.
  • the present composition is rectally or anally administered to the infant delivered via C-section, preferably in the form of a suppository, pill or tablet.
  • the present invention also provides a suppository, pill or tablet suitable for rectal administration to the infant, comprising the composition according as detailed here above.
  • Any base components commonly used for suppositories can be used as a base component of the suppository of the present invention, including oils and fats, waxes, and the like of animal, vegetable or mineral origins. They may be partially or totally synthesised materials.
  • composition of the present invention is for improving or stimulating the healthy gut microbiota and/or reducing health risks and/or prevention of disorders in infants delivered via C-section.
  • the composition is administered to the infant delivered via C-section starting at least in the first sixteen weeks after birth, preferably at least within twelve weeks after birth, more preferably at least within eight weeks after birth, even more preferably at least within four weeks after birth.
  • the present inventors observed that the composition of the present invention achieved levels of bifidobacteria in the C-section infants which resembled those of the reference group of vaginally-born infants in the first sixteen weeks after birth.
  • the treatment of the C-section delivery infant may be limited to the first sixteen weeks after birth, preferably the first twelve weeks after birth, more preferably the first eight weeks after birth, even more preferably the first four weeks after birth, particularly to the first two weeks after birth.
  • composition is administered to the infant delivered via C-section starting at least in the first two weeks after birth, preferably within the first week after birth, more preferably at least within 5 days after birth, even more preferably at least within 3 days after birth, most preferably at least within 2 days after birth. It shows from Figures 2 and 3 that the impact is most dramatic in the early onset.
  • administration to the C-section infant is started at least one day after birth.
  • Improvement of the gastrointestinal Bifidobacterium population in terms of numbers and diversity of species results in a reduced risk of occurrence of allergy, preferably food allergy, eczema (e.g. atopic dermatitis), asthma, allergic rhinitis and/or allergic conjunctivitis in infants delivered by C-section.
  • allergy preferably food allergy, eczema (e.g. atopic dermatitis), asthma, allergic rhinitis and/or allergic conjunctivitis in infants delivered by C-section.
  • Improvement of the gastrointestinal Bifidobacterium population in terms of numbers and diversity of species may also result in a reduced risk of infections, including gastrointestinal infections, and including reducing the occurrence and/or severity of infections, such as infections due to reduction of intestinal concentrations of pathogens particularly Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus haemolyticus, Streptococcus, Clostridium difficile, Bacilus subtilis, Pseudomonas aeruginosa, Enter obacter, Klebsiella, Acinetobacter, Proteus, Aeromonas and Escherichia coli.
  • This is achieved by (i) stimulating the growth of the lactic acid producing bacteria, (ii) decreasing the growth of pathogenic bacteria; and/or (iii) decreasing the adhesion of pathogenic bacteria to the intestinal epithelial cells and/or intestinal mucus.
  • C-section has also been associated with increased risks of developing allergies and obesity later in life, and the improvements in terms of swift microbiota restoration achieved by the invention thus also relate to reducing the risks of developing allergies and obesity later in life, meaning at an age exceeding the age at which the infant receives the composition, suitably exceeding the age by at least 12 months, more suitably by 24 months, by 36 months, by 5 years, most suitably by 8 years.
  • "later in life” means at toddler age, childhood age, adolescence age, or adult age.
  • 'scGOS' are short-chain galactooligosaccharides (Vivinal-GOSTM; Borculo Domo Ingredients, Netherlands; Degree of Polymerisation [DP] 2 - 8), 'lcFOS' are long-chain fructooligosaccharides (Raftiline HPTM, Orafti, Tienen, Belgium; average DP 22 - 25).
  • Figure 1 shows a comparison of the reference group and the control group in terms of total Bifidobacteria levels over the time period from day 3-5 until week 22, demonstrating that C-section infants (without any supplemented intervention) experience delayed colonisation of bifidobacteria compared to vaginally delivered and breast-fed infants.
  • Figure 2 shows the same graph from Figure 1 with the addition of the results from the prebiotic group and the synbiotic group. In these results, it can be observed that levels of bifidobacteria in the synbiotic group were achieved that resemble those observed from the reference group of infants.
  • Figure 3 shows the percentage of bifidobacteria in each group relative to total bacteria at Day 3-5, demonstrating that the effect of the synbiotic group generally described in Figure 2 could be observed from very early days of life.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Mycology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nutrition Science (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Emergency Medicine (AREA)
  • Pediatric Medicine (AREA)
  • Botany (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne un procédé pour (a) améliorer ou stimuler un microbiote intestinal sain, et/ou (b) réduire les risques pour la santé et/ou (c) prévenir des troubles, chez les nourrissons délivrés par césarienne (C), ledit procédé impliquant l'administration à un nourrisson délivré par césarienne d'une composition comprenant une quantité thérapeutiquement efficace d'au moins une espèce de Bifidobacterium probiotique choisie dans le groupe constitué de Bifidobacterium breve, Bifidobacterium longum sous-esp. longum, Bifidobacterium longum sous-esp. infantis et Bifidobacterium bifidum, laquelle composition est administrée au nourrisson délivré par césarienne en commençant au moins dans les seize premières semaines après la naissance, de préférence au moins dans les douze semaines après la naissance, mieux encore au moins dans les huit semaines après la naissance, mieux encore au moins au moins dans les quatre semaines après la naissance.
PCT/NL2015/050632 2015-09-11 2015-09-11 Procédé de stimulation de la santé du microbiote après une naissance non naturelle WO2017043962A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/NL2015/050632 WO2017043962A1 (fr) 2015-09-11 2015-09-11 Procédé de stimulation de la santé du microbiote après une naissance non naturelle

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/NL2015/050632 WO2017043962A1 (fr) 2015-09-11 2015-09-11 Procédé de stimulation de la santé du microbiote après une naissance non naturelle

Publications (1)

Publication Number Publication Date
WO2017043962A1 true WO2017043962A1 (fr) 2017-03-16

Family

ID=54478932

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/NL2015/050632 WO2017043962A1 (fr) 2015-09-11 2015-09-11 Procédé de stimulation de la santé du microbiote après une naissance non naturelle

Country Status (1)

Country Link
WO (1) WO2017043962A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019068356A1 (fr) * 2017-10-06 2019-04-11 N.V. Nutricia Promotion des fonctions cognitives après la naissance par césarienne
EP3646739A1 (fr) * 2018-11-01 2020-05-06 N.V. Nutricia Composition nutritionnelle comprenant de l'urée et des oligosaccharides non digestibles
CN111991428A (zh) * 2020-06-12 2020-11-27 郑州和合生物工程技术有限公司 一种具有改善哮喘作用的益生菌组合物及其制备方法
JPWO2019180965A1 (ja) * 2018-03-23 2021-02-04 森永乳業株式会社 学童期以降の高血糖に起因する疾患の予防のための乳幼児用組成物
EP4032536A1 (fr) 2021-01-26 2022-07-27 Probisearch, S.L.U. Composition probiotique pour nourrissons et ses utilisations
EP4159224A1 (fr) * 2017-06-30 2023-04-05 N.V. Nutricia Composition symbiotique de prévention de l'inflammation chronique
RU2804305C2 (ru) * 2018-11-01 2023-09-27 Н.В. Нютрисиа Пищевая композиция, содержащая мочевину и неперевариваемые олигосахариды
WO2023216181A1 (fr) * 2022-05-12 2023-11-16 N.V. Nutricia Amélioration du microbiote de nourrissons nés par césarienne

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1940250A1 (fr) 2005-10-21 2008-07-09 N.V. Nutricia Méthode pour stimuler la flore intestinale
WO2009151330A1 (fr) * 2008-06-13 2009-12-17 N.V. Nutricia Composition nutritionnelle destinée aux nourrissons nés par césarienne
US20100278781A1 (en) * 2007-06-15 2010-11-04 Sander Hougee Nutrition with non-viable bifidobacterium and non-digestible oligosaccharide

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1940250A1 (fr) 2005-10-21 2008-07-09 N.V. Nutricia Méthode pour stimuler la flore intestinale
EP2140771A1 (fr) * 2005-10-21 2010-01-06 N.V. Nutricia Méthode de stimulation de la flore intestinale chez des nourrissons nés par césarienne
EP2407036A1 (fr) * 2005-10-21 2012-01-18 N.V. Nutricia Procédé de stimulation de l'intégrité de la barrière intestinale après une naissance non naturelle
US8715769B2 (en) * 2005-10-21 2014-05-06 N.V. Nutricia Preventing diseases in infants delivered via caesarean section
EP2407036B1 (fr) * 2005-10-21 2015-11-04 N.V. Nutricia Procédé de stimulation de l'intégrité de la barrière intestinale après une naissance non naturelle
US20100278781A1 (en) * 2007-06-15 2010-11-04 Sander Hougee Nutrition with non-viable bifidobacterium and non-digestible oligosaccharide
WO2009151330A1 (fr) * 2008-06-13 2009-12-17 N.V. Nutricia Composition nutritionnelle destinée aux nourrissons nés par césarienne

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
DOMINGUEZ-BELLO ET AL.: "Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns", PNAS, vol. 107, no. 26, 2010, pages 11971 - 11975
HAKANSSON ET AL.: "Caesarean section increases the risk of hospital care in childhood for asthma and gastroenteritis", CLIN. EXP. ALLERGY, vol. 33, 2003, pages 757 - 764
KUITUNEN M ET AL: "Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort", JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, ELSEVIER, AMSTERDAM, NL, vol. 123, no. 2, 1 February 2009 (2009-02-01), pages 335 - 341, XP025907147, ISSN: 0091-6749, [retrieved on 20090108], DOI: 10.1016/J.JACI.2008.11.019 *
L. PROSKY ET AL., J. ASSOC. ANAL. CHEM, vol. 71, 1988, pages 1017 - 1023
LAUBEREAU ET AL.: "Caesarean section and gastrointestinal symptoms, atopic dermatitis and sensitisation during the first year of life''", ARCH. DIS. CHILD, vol. 89, 2004, pages 993 - 997

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4159224A1 (fr) * 2017-06-30 2023-04-05 N.V. Nutricia Composition symbiotique de prévention de l'inflammation chronique
WO2019068924A1 (fr) * 2017-10-06 2019-04-11 N.V. Nutricia Promotion de la fonction cognitive après la naissance par césarienne
WO2019068356A1 (fr) * 2017-10-06 2019-04-11 N.V. Nutricia Promotion des fonctions cognitives après la naissance par césarienne
JPWO2019180965A1 (ja) * 2018-03-23 2021-02-04 森永乳業株式会社 学童期以降の高血糖に起因する疾患の予防のための乳幼児用組成物
JP7266580B2 (ja) 2018-03-23 2023-04-28 森永乳業株式会社 学童期以降の高血糖に起因する疾患の予防のための乳幼児用組成物
RU2804305C2 (ru) * 2018-11-01 2023-09-27 Н.В. Нютрисиа Пищевая композиция, содержащая мочевину и неперевариваемые олигосахариды
EP3646739A1 (fr) * 2018-11-01 2020-05-06 N.V. Nutricia Composition nutritionnelle comprenant de l'urée et des oligosaccharides non digestibles
WO2020089463A1 (fr) * 2018-11-01 2020-05-07 N.V. Nutricia Composition nutritionnelle comprenant de l'urée et des oligosaccharides non digestibles
CN113015440A (zh) * 2018-11-01 2021-06-22 N·V·努特里奇亚 包含尿素和不可消化寡糖的营养组合物
CN113015440B (zh) * 2018-11-01 2024-04-05 N·V·努特里奇亚 包含尿素和不可消化寡糖的营养组合物
EP4321211A3 (fr) * 2018-11-01 2024-03-20 N.V. Nutricia Composition nutritionnelle comprenant de l'urée et des oligosaccharides non digestibles
EP3873237B1 (fr) * 2018-11-01 2023-09-20 N.V. Nutricia Composition nutritionnelle comprenant de l'urée et des oligosaccharides non digestibles
CN111991428A (zh) * 2020-06-12 2020-11-27 郑州和合生物工程技术有限公司 一种具有改善哮喘作用的益生菌组合物及其制备方法
WO2022161928A1 (fr) 2021-01-26 2022-08-04 Probisearch, S.L.U. Composition probiotique à base de lactobacillus salivarius et de bifidobacterium longum et ses utilisations
EP4032536A1 (fr) 2021-01-26 2022-07-27 Probisearch, S.L.U. Composition probiotique pour nourrissons et ses utilisations
WO2023216181A1 (fr) * 2022-05-12 2023-11-16 N.V. Nutricia Amélioration du microbiote de nourrissons nés par césarienne

Similar Documents

Publication Publication Date Title
ES2560291T3 (es) Método para estimular la integridad de la barrera intestinal después de un nacimiento no natural
TWI342779B (en) Nutritional formula for optimal gut barrier function
US11135232B2 (en) Compositions for use in the prevention or treatment of necrotizing enterocolitis in infants and young children
RU2761533C2 (ru) Система детской смеси с адаптивными концентрациями олигосахаридов грудного молока (огм)
US10940158B2 (en) Compositions for use in the prevention or treatment of necrotizing enterocolitis in infants or young children born by C-section
AU2012325060B2 (en) Composition for use in brain growth and/or cognitive and/or psychomotor development
WO2017043962A1 (fr) Procédé de stimulation de la santé du microbiote après une naissance non naturelle
AU2012325072B2 (en) Composition for use in increasing insulin sensitivity and/or reducing insulin resistance
TW201233334A (en) Human milk oligosaccharides to promote growth of beneficial bacteria
EP3074020A1 (fr) Compositions destinée à la prévention ou au traitement de l'entérocolite nécrosante chez les nourrissons et les jeunes enfants
TW201304692A (zh) 增進有益微生物相生長之益生菌及人乳寡醣之合益素（ｓｙｎｂｉｏｔｉｃ）組合
TWI639387B (zh) 用於預防胃腸道受傷及／或促進胃腸道治癒之半乳寡糖
EP2162020A2 (fr) Nutrition avec une bifidobactérie non viable et un oligosaccharide non digérable
TW201438720A (zh) 增強學習及記憶力之膳食寡糖
WO2021260162A1 (fr) Composition symbiotique
RU2694195C2 (ru) Питательная композиция для применения при активации формирования и/или регенерации кишечника и/или печени
RU2695699C2 (ru) Питательная композиция с низким содержанием среднецепочечных жирных кислот в определенных соотношениях и ее применение
WO2017043963A1 (fr) Ensemble d'éléments visant à stimuler la santé du microbiote après une naissance non naturelle
US20220000892A1 (en) Infant nutritional composition for use in the enhancement of pancreatic maturation and insulin biosynthesis
US20220409645A1 (en) Compositions for use in the reduction of pain and/or perception of pain in infants and young children
WO2019068924A1 (fr) Promotion de la fonction cognitive après la naissance par césarienne
RU2808973C2 (ru) Питательная композиция для младенцев, предназначенная для применения с целью улучшения созревания поджелудочной железы и биосинтеза инсулина
TW201316983A (zh) 用於促進腸血管新生作用及養分吸收及經腸給養耐受性、及／或預防及／或治療腸發炎、及／或腸損傷及手術後恢復之組合物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15791782

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15791782

Country of ref document: EP

Kind code of ref document: A1