EP3820308A1 - Composition nutritionnelle destinée à être utilisée dans le traitement de la diarrhée, sa préparation et procédé de traitement - Google Patents

Composition nutritionnelle destinée à être utilisée dans le traitement de la diarrhée, sa préparation et procédé de traitement

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Publication number
EP3820308A1
EP3820308A1 EP18753474.8A EP18753474A EP3820308A1 EP 3820308 A1 EP3820308 A1 EP 3820308A1 EP 18753474 A EP18753474 A EP 18753474A EP 3820308 A1 EP3820308 A1 EP 3820308A1
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EP
European Patent Office
Prior art keywords
oligosaccharides
diarrhea
nutritional composition
treatment
galacto
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
EP18753474.8A
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German (de)
English (en)
Inventor
Catharina Theresia Knipping
Bernd Stahl
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Nutricia NV
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Nutricia NV
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Publication date
Application filed by Nutricia NV filed Critical Nutricia NV
Publication of EP3820308A1 publication Critical patent/EP3820308A1/fr
Pending legal-status Critical Current

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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
    • A23L33/40—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
    • A61K31/70—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
    • 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 relates to infant nutrition with non-digestible oligosaccharides, in particular to the use thereof for treatment of virus induced diarrhea.
  • Viral infections are common among people of all ages but often seem to be concentrated in infants and children. Many viral infections result in fever and body aches or discomfort and are not that serious and most children with viral infections get better without treatment. Particularly during infancy, it is difficult for parents to tell whether their infant is ill with a potentially serious infection and needs immediate medical care.
  • Rotavirus is the main causative agent of acute diarrheal disease in infants, which can lead to dehydration or to more severe complications and even to death if left untreated.
  • RV pathogenesis is still unclear and RV vaccines are not globally implemented, the modulation by nutritional interventions with bioactive components is of interest.
  • Recent studies have suggested the possible role of HMOS in the protection against RV-associated diarrhea (Laucirica et al. J Nutr 2017; 147:1709-1714; Comstock et al. J Nutr Biochem Mol Genet Mech 2017; 147:1041-1047.
  • Human milk is the preferred food for infants. Human milk provides several bioactive factors that benefit the relatively immature immune system of neonates early in life. These components have been categorized into two different groups according to either their protective role or their ability to promote maturation. In this sense, human milk oligosaccharides (HMOS) are considered to play a part both in protection and maturation. However, it is not always possible or desirable to breastfeed an infant. In such cases infant formulae or follow on formulae are a good alternative. These formulae should have an optimal composition in order to mimic the beneficial effects of human milk as close as possible.
  • HMOS human milk oligosaccharides
  • HMOS The 162 structures of HMOS discovered to date and described in Urashima et al. (Trends in Glycoscience and Glycotechnolology, 2018, 30; 172, SE51 -SE65) exhibit a lactose, polylactosamine or lacto-N-biose core, which can be further bound to either fucose or sialic acids or both. This structure confers on them a high chemical variability and protection from digestion. Therefore, the majority of HMOS are neither absorbed nor metabolized in the proximal gut and reach the distal gut undigested to exert prebiotic effects on certain bacterial populations, to reinforce the intestinal barrier and to protect against enteropathogen infections.
  • HMOS are present in human breast milk in a relatively high proportion (5-20 g/L).
  • the most abundant HMOS is 2’-fucosyllactose (2'-FL), representing ⁇ 20% of the total oligosaccharides in human breast milk.
  • 2'-FL 2’-fucosyllactose
  • In vitro and in vivo studies with 2’-FL have evidenced its immunomodulatory effects, which include promoting anti- inflammatory activities (He et al. Gut 2016; 65:33-46 and the inhibition of the colonization of pathogens (Ruiz-Palacios et al. J Biol Chem 2003; 278:141 12-20.
  • WO 2016/139333 concerns nutritional compositions comprising a fucosylated oligosaccharide such as 2’-fucosyllactose and a particular N-actelyated oligosaccharide such as lacto-N-neotetraose (LNnT) for use against gastrointestinal infections and inflammations in infants or young children.
  • a fucosylated oligosaccharide such as 2’-fucosyllactose
  • N-actelyated oligosaccharide such as lacto-N-neotetraose (LNnT)
  • the present invention thus concerns a method for the treatment of virus induced diarrhea in a human subject by administering a nutritional composition that comprises a fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose.
  • the invention concerns a nutritional composition
  • a fucosylated human milk oligosaccharide preferably 2’-fucosyllactose, for use in the treatment of virus induced diarrhea in a human subject.
  • the virus induced diarrhea is rotavirus induced diarrhea.
  • the invention can also be worded as the use of a fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose, for the preparation of a nutritional composition for the treatment of virus induced diarrhea in a human subject.
  • a fucosylated human milk oligosaccharide preferably 2’-fucosyllactose
  • the amount of the fucosylated HMO, preferably 2’-fucosyllactose is preferably an effective amount to treat virus induced diarrhea in a human subject and/or an effective amount to reduce the severity of the virus induced diarrhea and/or an effective amount to shorten the duration of the virus induced diarrhea.
  • Prebiotics are typically indigestible sugar-type compounds such as non-digestible oligosaccharides (NDOs). These compounds pass through the first part of the gastrointestinal tract substantially without being digested. In the intestine these compounds are fermented by the microbiota releasing, amongst others, short chain fatty acids which are adsorbed by the human body.
  • NDOs non-digestible oligosaccharides
  • NDO neurode-derived neurode-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide-derived neuropeptide (GOS) oligosaccharides (GOS) oligosaccharides (GOS).
  • GOS human milk oligosaccharides
  • Human milk is the preferred food for infants and is also denoted as the golden standards. Human milk contains a particularly high level of oligosaccharides of roughly 10 to 15 g/L, which is typically much more than the level of NDO in the milk from domestic animals. Also, compared to the NDOs in the milk of domestic animals, HMOS are structurally different. Human NDO is very complex and consists of a heterogenic group of many different compounds with diverse sugar composition. Because of their complex and polymorphic structure, large-scale synthesis is complicated. It is therefore not yet technically and economically feasible to prepare compositions, such as infant formulas, with NDO composition identical to human milk. In the method or use according to the present invention, a fucosylated non-digestible human milk oligosaccharide is used.
  • Fucosyllactose is a fucosylated non-digestible oligosaccharide present in human milk. It is not present in bovine milk. It consists of three monose units, fucose, galactose and glucose linked together. Lactose is a galactose unit linked to a glucose unit via a beta 1 ,4 linkage. A fucose unit is linked to a galactose unit of a lactose molecule via an alpha 1 ,2 linkage (2’-fucosyllactose, 2’-FL) or via an alpha 1 ,3 linkage to the glucose unit of a lactose (3-Fucosyllactose, 3-FL). 2’FL is the most abundant NDO in human milk. The HMOS used in the current invention is 2’-FL.
  • ⁇ -L-Fuc-(1 - 2) ⁇ -D-Gal-(1 ®4)-D-Glc) is commercially available for instance from Sigma- Aldrich. Alternatively, it can be isolated from human milk, for example as described in Andersson & Donald, 1981 , J Chromatogr. 21 1 :170-1744, or produced by genetically modified micro-organisms, for example as described in Albermann et al, 2001 , Carbohydrate Res. 334:97-103.
  • a composition according to the invention comprises 1 mg to 3 g 2’-FL per 100 ml, more preferably 10 mg to 2 g, even more preferably 20 mg to 100 mg 2’-FL per 100 ml.
  • the present composition preferably comprises 0.007 wt.% to 20 wt.% 2’-FL, more preferably 0.07 wt.% to 10 wt.%, even more preferably 0.15 wt.% to 1 wt.%.
  • a lower amount of fucosyllactose will be less effective in ameliorating virus induced diarrhea, whereas a too high amount will result in unnecessary high costs of the product.
  • the nutritional composition for use according to the present invention does not comprise lacto-N-neotetraose (LNnT). In one embodiment, the nutritional composition for use according to the present invention does not comprise a human milk oligosaccharide other than 2’- FL.
  • the nutritional composition preferably also comprises non-digestible oligosaccharides other than HMOS
  • Non-digestible oligosaccharides other than HMOS can have an effect on stool consistency and in particular an effect of loosening stool and as such have an effect that would lead to the apparent contrary finding that diarrhea would not be ameliorated.
  • non-digestible oligosaccharides other than HMO in particular when correcting for the intrinsic effect on fecal consistency of non-digestible oligosaccharides other than HMO, it was found that their inclusion had an additional role in significantly reducing the severity score and duration of the diarrhea.
  • 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 selected from the group consisting of fructo-oligosaccharides, galacto-oligosaccharides, xylo-oligosaccharides, arabino-oligosaccharides, arabinogalacto- oligosaccharides, gluco-oligosaccharides, chito-oligosaccharides, glucomanno-oligosaccharides, galactomanno-oligosaccharides and mannan-oligosaccharides.
  • the group of fructo- oligosaccharides includes inulins and the group of galacto-oligosaccharides includes transgalacto- oligosaccharides or beta-galacto-oligosaccharides.
  • the present composition comprises fructo-oligosaccharides (FOS), and/or galacto- oligosaccharides (GOS), preferably the galacto-oligosaccharides comprise beta-galacto- oligosaccharides and/or alpha galactooligosaccharides. More preferably the fructo- oligosaccharides are long chain fructo-oligosaccharides (IcFOS). More preferably the galacto- oligosaccharides are short chain galacto-oligosaccharides and the beta-galacto-oligosaccharides are short chain beta-galacto-oligosaccharides.
  • the composition comprises long chain fructo oligosaccharides and short chain galacto-oligosaccharides.
  • the weight ratio of short chain galacto-oligosaccharides and long chain fructo oligosaccharides lies preferably between 100:1 and 1 :10, preferably between 20:1 and 1 :1 , preferably is about 9:1 .
  • the galacto-oligosaccharides preferably are beta-galacto-oligosaccharides.
  • the present composition comprises beta-galacto-oligosaccharides ([galactosejn-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(TM) (Borculo Domo Ingredients, Netherlands). Another suitable source is Bi2Munno (Classado).
  • the galacto-oligosaccharides comprise beta-1 ,3, beta-1 ,4 and/or beta-1 ,6 linkages.
  • galacto-oligosaccharides comprise at least 80 % beta-1 ,4 and beta-1 ,6 linkages based on total linkages, more preferably at least 90 %.
  • the galacto-oligosaccharides comprise at least 50 % beta-1 ,3 linkages based on total linkages, more preferably at least 60 % based on total linkages.
  • 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.
  • 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, preferably galacto-oligosaccharides and fructo-oligosaccharide 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 composition comprises a combination of a fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose, short chain galacto-oligosaccharides and long chain fructo oligosaccharides.
  • the weight ratio of the sum of short chain galacto-oligosaccharides and long chain fructo oligosaccharides to 2’-fucosyllactose contained in the nutritional composition lies preferably between 20:1 and 1 :100, preferably between 10:1 and 1 :50, more preferably between 4:1 and 1 :20, most preferably between 1 :1 and 1 :15.
  • 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 (DPA, 22:5 n3), preferably DHA, EPA and/or ARA.
  • LC-PUFAs have a further beneficial effect on improving intestinal barrier integrity.
  • the preferred content of LC-PUFA in the present composition does not exceed 15 wt.% of total fatty acids, preferably does not exceed 10 wt.%, even more preferably does not exceed 5 wt.%.
  • the present composition comprises at least 0.2 wt.%, preferably at least 0.25 wt.%, more preferably at least 0.35 wt.%, even more preferably at least 0.5 wt.% LC-PUFA of total fatty acids, more preferably DHA.
  • the present composition preferably comprises ARA and DHA, wherein the weight ratio ARA/DHA preferably is above 0.25, preferably above 0.5, more preferably 0.75 - 2, even more preferably 0.75-1 .25.
  • the weight ratio is preferably below 20, more preferably between 0.5 and 5.
  • the amount of DHA is preferably above 0.2 wt.%, more preferably above 0.3 wt.%, more preferably at least 0.35 wt.%, even more preferably 0.35 - 0.6 wt.% on total fatty acids.
  • the present invention advantageously concerns a composition for the indicated use wherein the lipid provides 5 to 50% of the total calories, the protein provides 5 to 50% of the total calories, and the carbohydrate provides 15 to 90% of the total calories.
  • the lipid provides 35 to 50% of the total calories
  • the protein provides 7.5 to 12.5% of the total calories
  • the carbohydrate provides 40 to 55% of the total calories.
  • the present 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 comprising 2’- FL is not human milk.
  • the present composition preferably comprises protein.
  • the protein component used in the nutritional preparation are preferably selected from the group consisting of non-human animal proteins (preferably milk proteins, preferably proteins from cow’s milk), vegetable proteins (preferably soy protein and/or rice protein), free amino acids and mixtures thereof.
  • the present composition preferably contains casein, whey, hydrolysed casein and/or hydrolysed whey protein.
  • the protein comprises intact proteins, more preferably intact bovine whey proteins and/or intact bovine casein proteins.
  • the present composition preferably comprises digestible carbohydrates.
  • the present composition preferably comprises a digestible carbohydrate component, wherein at least 35 wt.%, more preferably at least 50 wt.%, more preferably at least 75 wt.%, even more preferably at least 90 wt.%, most preferably at least 95 wt.% is lactose.
  • the present composition preferably comprises at least 25 grams lactose per 100 gram dry weight of the present composition, preferably at least 40 grams lactose/100 gram.
  • the nutritional composition When in liquid for, the nutritional composition 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 amount of nutritional composition administered per day is preferably between 50 and 2000 ml, more preferably between 200 and 1500, most preferably between 400 and 1000 ml.
  • the present invention concerns a supplement, suitable to fortify human milk, to fortify human milk fortified with a standard human milk fortifier or to fortify a standard preterm formula.
  • a supplement does not comprise all macro- and micronutrients needed for preterm infants so as to achieve a growth similar to fetal growth coupled with satisfactory functional development.
  • preterm herein is synonymous for prematurely born and means any human infant born before the 37 th week of gestation.
  • the nutritional composition according to the present invention or for use according to the present invention comprises protein, fat and/or digestible carbohydrates and is selected from the group consisting of an infant starter formula, an infant follow on formula, a toddler milk, a preterm formula, a post discharge formula and a human milk fortifier.
  • virus induced diarrhea is treated by administering a nutritional composition comprising a fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose.
  • a nutritional composition comprising a fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose.
  • the diarrhea that is treated is induced by rotavirus, also referred to as rotavirus induced diarrhea.
  • the treatment of virus induced diarrhea is reducing the severity of the virus induced diarrhea. In a further preferred embodiment, the treatment of virus induced diarrhea is shortening the duration of the virus induced diarrhea. Preferably, the treatment of virus induced diarrhea is reducing of the severity of the virus induced diarrhea and shortening the duration of the virus induced diarrhea.
  • the administration or use of the fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose is to reduce the severity of the virus induced diarrhea.
  • the administration or use of the fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose is to shorten the duration of the virus induced diarrhea.
  • the administration or use of fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose is to reduce the severity of the virus induced diarrhea and to shorten the duration of the virus induced diarrhea.
  • the nutritional composition for use according to the present invention is for use in a human subject.
  • the human subject is an infant or a toddler.
  • An infant is a human subject with an age form 0-12 months.
  • a toddler is a human subject with an age from 12-36 months.
  • the human subject is a preterm or prematurely born infant.
  • this subgroup of infants may benefit from being administered the fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose, or a combination of the fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose, and long chain fructo oligosaccharides and short chain galacto- oligosaccharides since organs making up the intestinal tract of preterms are vulnerable and immature, as opposed to term-born infants and thus in need of shortened duration of diarrhea and/or less severe diarrhea as treatment would it occur.
  • the human subject is administered the fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose, or the nutritional composition comprising the fucosylated human milk oligosaccharide, preferably 2’-fucosyllactose, on a daily basis.
  • the administration of the nutritional composition comprising the fucosylated human milk oligosaccharide, preferably 2’- fucosyllactose, or the use thereof preferably commences prior to the virus induced diarrhea occurs and spans the time period the subject can be diagnosed with diarrhea.
  • the human subject is vaginally-born, also known as naturally born.
  • the reduction in the severity of the virus induced diarrhea and/or the shortened duration of the virus induced diarrhea is accompanied by improved virus elimination by the human subject or reduced viral particle counts in the stool. It was found by the inventors that the addition of 2'-fucosyllactose, short chain galacto-oligosaccharides and long chain fructo- oligosaccharides reduced shedding of viral particles in the feces by the human subject. This is in particular advantageous in the prevention of virus transmittal or a second round of virus-induced diarrhea via self-contamination following the primary virus infection, like rotavirus, via the stool.
  • the reduction in the severity of the virus induced diarrhea and/or the shortened duration of the virus induced diarrhea is accompanied by reduced virus elimination by the human subject.
  • the present composition is preferably enterally administered, more preferably orally.
  • the present composition is preferably a nutritional formula, preferably an infant formula.
  • the present composition can advantageously be applied as a complete nutrition for infants.
  • the present composition preferably comprises lipid, protein, and carbohydrate and is preferably administered in liquid form.
  • the present invention includes dry compositions, e.g. powders, which are accompanied with instructions as to admix said dry compositions, in particular nutritional formula, with a suitable liquid, e.g. water.
  • Newborn rats were distributed into five groups of 24 animals each: the reference (REF) group, rotavirus-infected (RV) group, and 3 rotavirus-infected groups supplemented with: a) a mixture of scGOS and IcFOS (RV+GOS/FOS group); b) 2 -FL (RV+2’-FL group); and c) both scGOS/lcFOS and 2 -FL (RV+GOS/FOS+2’-FL group).
  • REF reference
  • RV rotavirus-infected
  • 3 rotavirus-infected groups supplemented with: a) a mixture of scGOS and IcFOS (RV+GOS/FOS group); b) 2 -FL (RV+2’-FL group); and c) both scGOS/lcFOS and 2 -FL (RV+GOS/FOS+2’-FL group).
  • Suckling rats were orally administered once daily with the same normalized volume/body weight of all products (4.5 pL/g/day), from the second to the sixteenth day of life, corresponding to the strict lactation period.
  • the RV+GOS/FOS group was supplemented with 0.8 g of scGOS/lcFOS/100 g of body weight.
  • the RV+2’-FL group was supplemented with 0.2 g of 2’-FL/100 g of body weight.
  • the RV+GOS/FOS+2’-FL group received both products at the same doses as when given separately and maintaining the volume of administration (4.5 pL/g/day).
  • the REF and RV groups were administered with a matched volume of water.
  • the RV (simian SA-1 1) was obtained as previously described (Perez-Cano et al. Pediatr Res 2007;62:658-63), and inoculated at day 5 of life (4x10 8 Tissue Culture Infectious Dose 50 [TCID50]/rat) in all the experimental groups with the exception of the REF group, which received the same volume of phosphate-buffered solution (PBS) under the same conditions.
  • PBS phosphate-buffered solution
  • Fecal sampling was performed once daily throughout the study (from day 4 to day 16 of life) by gently pressing and massaging the abdomen. Fecal samples were stored at -20 °C for the analysis of RV shedding. Severity of diarrhea was expressed by fecal weight and by scoring fecal samples from 1 to 4 (diarrhea index [Dl]) based on color, texture and amount, as follows: normal feces (1 ); soft yellow-green feces (2); totally loose yellow-green feces (3); high amount of watery feces (4). Scores > 2 indicate diarrheic feces, whereas scores ⁇ 2 indicate absence of diarrhea.
  • the severity- area under the curve (S-AUC) during days 5-1 1 coinciding with the period in which animals displayed diarrhea, was calculated as a global value of severity.
  • the maximum severity (MS) was defined as the highest score during the diarrhea period.
  • the diarrhea period (DP) was calculated by counting the number of days in which the animals displayed Dl > 2.
  • the Dl, S-AUC, MS and DP were normalized (nDI, nS-AUC, nMS and nDP) in RV+GOS/FOS and RV+GOS/FOS+2'-FL groups, taking into account the basal values before and after the diarrhea period because of intrinsic fecal aspects of GOS/FOS supplementation, as previously described (Rigo-Adrover et al. Eur J Nutr 2017;56:1657-70).
  • the Statistical Package for the Social Sciences (SPSS v22.0) (IBM, Chicago, IL, USA) was used for statistical analysis. Data was tested for homogeneity of variance and normality distribution by the Levene’s and Shapiro-Wilk tests, respectively. When data was homogeneous and had a normal behavior, conventional one-way ANOVA test followed by the post hoc Bonferroni was performed. Otherwise, the nonparametric Kruskal-Wallis test followed by the post hoc Mann-Whitney U (MWU) test were performed. Finally, the chi-square test was used to compare frequencies of diarrhea incidence. Significant differences were established when p ⁇ 0.05.
  • the RV infection did not produce any significant change in growth either at the peak of diarrhea (day 8) or at the end of the study (day 16), as shown by the results in body weight, body/tail ratio, BMI and Lee Index (Table 1).
  • the group supplemented with scGOS/lcFOS had a slightly higher body weight at the end of the study (day 16, p ⁇ 0.05), and although none of these growth changes modified the BMI, some differences were seen in the body/tail length ratio and the Lee Index. All supplementations increased the body/tail length ratio compared to REF or RV at some time point. Moreover, the Lee Index was decreased exclusively at the peak of diarrhea compared to REF. Table 1. Growth-associated variables
  • Rats inoculated with RV displayed diarrheic feces from days 6 to 1 1 of life, the highest score being at day 8.
  • GOS/FOS induced changes in fecal consistency, thereby increasing the number of feces considered as diarrheic (Dl > 2) before, during and after the diarrheic process (Rigo-Adrover et al. Eur J Nutr 2017;56:1657-70).
  • the supplementation with GOS/FOS and GOS/FOS+2’-FL showed a tendency to reduce the severity of diarrhea at the maximum affectation point.
  • the fecal weight was also measured as an objective severity variable of the diarrheic process.
  • animals receiving GOS/FOS and GOS/FOS+2’-FL had a higher fecal weight compared to both the REF and RV groups, which is likely to be related to the previously direct changes reported in the fecal consistency.
  • the RV group After infecting with the virus (corresponding to days 6-1 1 of life), the RV group showed an increased fecal weight (p ⁇ 0.05).
  • the effects of the supplementations with oligosaccharides were seen at days 6-8, reducing this increase of fecal weight, although only statistical differences in the supplementation with 2’-FL were attained (p ⁇ 0.05).
  • Example 2 Infant formula for reducing the severity of rotavirus induced diarrhea or shortening rotavirus induced diarrhea.
  • An infant formula according to the invention comprising per 100 ml (13.9 dry weight):
  • non-digestible oligosaccharides of which 60 mg 2’-fucosyllactose and 480 mg beta-galacto- oligosaccharides, and 60 mg fructo-oligosaccharides

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Abstract

L'invention concerne une composition comprenant un oligosaccharide de lait humain fucosylé, de préférence le 2'-fucusyllactose, destinée à être utilisée dans le traitement de la diarrhée induite par un virus. La composition peut être une formule pour nourrissons. L'invention concerne également l'utilisation d'un oligosaccharide de lait humain fucosylé pour la préparation d'une composition nutritionnelle et le traitement de la diarrhée induite par un virus chez un sujet humain.
EP18753474.8A 2018-07-12 2018-07-12 Composition nutritionnelle destinée à être utilisée dans le traitement de la diarrhée, sa préparation et procédé de traitement Pending EP3820308A1 (fr)

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PCT/NL2018/050478 WO2020013684A1 (fr) 2018-07-12 2018-07-12 Composition nutritionnelle destinée à être utilisée dans le traitement de la diarrhée, sa préparation et procédé de traitement

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EP3888661A1 (fr) * 2020-03-31 2021-10-06 FrieslandCampina Nederland B.V. Compositions comprenant du 2-fucosyllactose pour la prévention des infections virales

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5827526A (en) * 1995-07-11 1998-10-27 Abbott Laboratories Use of indigestible oligosaccharides to prevent gastrointestinal infections and reduce duration of diarrhea in humans
EP2453901B1 (fr) * 2009-07-15 2014-09-10 N.V. Nutricia Fucosyllactose utilisé en tant qu'oligosaccharide non digestible identique au lait maternel pour la prévention et/ou le traitement d'infections virales
NZ612472A (en) * 2010-12-31 2015-02-27 Abbott Lab Nutritional compositions comprising human milk oligosaccharides and nucleotides and uses thereof for treating and/or preventing enteric viral infection
ES2709599T3 (es) * 2013-02-21 2019-04-16 Jennewein Biotechnologie Gmbh Oligosacáridos fucosilados sintéticos o recombinantes para uso en el tratamiento de infecciones
DE202016008919U1 (de) 2015-03-05 2020-09-07 Société des Produits Nestlé S.A. Zusammensetzungen zur Verwendung bei der Prävention oder Behandlung von gastrointestinalen Infektionen/Entzündungen bei Säuglingen oder Kleinkindern
CN109562117A (zh) * 2016-08-04 2019-04-02 雀巢产品技术援助有限公司 具有2FL和LNnT的营养组合物，用于通过作用于肠道微生物群生态失调来预防和/或治疗非轮状病毒腹泻

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WO2020013684A1 (fr) 2020-01-16
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