Agents, compositions, and methods for supporting behavioral development

Abstract

The present invention provides one or more human milk oligosaccharides (HMOs) for use in supporting behavioral development in a subject, the HMOs comprising: (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP-I). , lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

Description

[Technical Field]

[0001] The present invention relates to agents, compositions and methods for supporting behavioral development, and further relates to agents, compositions and methods for improving social-emotional skills, reducing negative affectivity and preventing anxiety and / or mood disorders. [Background technology]

[0002] Social-emotional skills develop simultaneously from infancy through childhood and include behaviors that reflect a child's emotional growth and ability to interact effectively with others. Social-emotional development includes the development of emotional skills and abilities, including mood. Emotional development can refer to the ability to effectively regulate emotions to achieve goals.

[0003] It is believed that a lack of social and emotional skills can have undesirable consequences in children's behavioral development, leading to aggressive or disruptive behavior, loneliness, anxiety, and depression. Many anxiety disorders begin in early childhood (see, for example, Clark C., et al., 2007. Arch Gen Psychatry. 64(6), pp. 668-678 and Mian N., et al., 2012. J. Anxiety Disord. 26(1), pp. 102-110).

[0004] Although multiple studies have shown an association between individual compounds present in human breast milk and behavioral development, the relationship between early life nutrition and its effects on the behavioral development of infants, toddlers and / or young children remains unclear (see, e.g., Wachs, TD, 2000. International Journal of Behavioral Development, 24(4), pp. 435-441).

[0005] Thus, new nutritional interventions are needed to promote behavioral development and / or improve social-emotional skills, for example, in infants, toddlers, or young children. There is a need to provide such benefits in a manner that does not induce side effects and / or is easy to deliver and acceptable to parents or health care professionals. There is also a need to provide such benefits in a manner that keeps the costs associated with such delivery reasonable and affordable for most people. Summary of the Invention

[0006] We surprisingly found that specific human milk oligosaccharides (HMOs) are associated with reduced negative affect in breastfed infants. The HMOs we identified have not previously been reported to be associated with social-emotional outcomes.

[0007] Because infancy is a crucial age for social-emotional milestones, such as experiencing fear, the emergence of separation anxiety from primary caregivers, visual recognition of familiar figures, and letting parents know when happy versus when upset, reducing negative emotions can be beneficial for behavioral development.

[0008] In one aspect, the present invention provides one or more human milk oligosaccharides (HMOs) for use in supporting behavioral development in a subject.

[0009] In one aspect, the present invention provides one or more human milk oligosaccharides (HMOs) for use in supporting behavioral development in a subject, the HMOs comprising: (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), and lacto-N-fucopentaose II (LNFPII), LNFP-I (lacto-N-fucopentaose I ( The present invention provides one or more HMOs comprising or consisting of lacto-N-fucopentaose III (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

[0010] In another aspect, the present invention provides the use of one or more human milk oligosaccharides (HMOs) for supporting behavioral development in a subject.

[0011] In another aspect, the present invention provides a method of supporting behavioral development in a subject, the method comprising administering to the subject one or more human milk oligosaccharides (HMOs).

[0012] In another aspect, the present invention relates to the use of one or more HMOs for improving social and emotional skills, wherein the one or more HMOs are selected from the group consisting of (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LN The present invention provides a method for the preparation of a lactofuctose-N-fucopentaose (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

[0013] In another aspect, the present invention relates to the use of one or more HMOs for reducing negative emotions, wherein the one or more HMOs are selected from the group consisting of: (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP The present invention provides a use comprising or consisting of lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

[0014] Any suitable HMO as described herein may be used. Suitably, the one or more HMOs comprise or consist of a combination of fucosylated HMOs. Suitably, the one or more HMOs comprise or consist of (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI). In some embodiments, the one or more HMOs comprise or consist of LNDFHI, hi some embodiments, the one or more HMOs comprise or consist of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI.

[0015] The one or more HMOs may be administered by any suitable means and in any suitable amount. Preferably, the one or more HMOs are administered orally. Preferably, the one or more HMOs are administered separately, simultaneously, or sequentially. In a preferred embodiment, the one or more HMOs are administered simultaneously. Preferably, the one or more HMOs are administered to a subject in a total amount of about 0.5 g / day to about 10 g / day. Preferably, the combination of fucosylated HMOs is administered to a subject in a total amount of about 0.5 g / day to about 10 g / day. Preferably, LNDFHI is administered to a subject in an amount of about 0.1 g / day to about 5 g / day. Preferably, 2'FL is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, 3FL is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, LDFT is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, and LNFPII is administered to the subject in an amount of about 0.1 g / day to about 5 g / day. LNFP-I is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, LNFP-III is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, LND-I is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, MFLNH-III is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, LNFP-V is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, LNnDFH is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, and / or LNFP-VI is administered to the subject in an amount of about 0.1 g / day to about 5 g / day.

[0016] The one or more HMOs may be provided in any suitable form. Preferably, the one or more HMOs are in the form of a nutritional composition. In some embodiments, the nutritional composition is an infant formula, a follow-on formula, or a growing-up milk. In a preferred embodiment, the nutritional composition is an infant formula. Preferably, the starter infant formula, the follow-on formula, and the growing-up milk each have a content of about 60 kcal / 100 mL to about 80 kcal / 100 mL and contain protein in an amount of about 1.5 g / 100 kcal to about 2.5 g / 100 kcal, carbohydrates in an amount of about 8 g / 100 kcal to about 15 g / 100 kcal, and lipids in an amount of about 3 g / 100 kcal to about 8 g / 100 kcal.

[0017] The nutritional composition may contain one or more HMOs in any suitable amount. Preferably, the nutritional composition contains one or more HMOs in a total amount of about 0.5 g / L to about 10 g / L. Preferably, the nutritional composition contains a combination of fucosylated HMOs in a total amount of about 0.5 g / L to about 10 g / L. Preferably, the nutritional composition contains LNDFHI in an amount of about 0.2 g / L to about 2.0 g / L. Preferably, the nutritional composition contains 2'FL in an amount of about 0.5 g / L to about 3.0 g / L, 3FL in an amount of about 0.2 g / L to about 2.0 g / L, LDFT in an amount of about 0.05 g / L to about 0.5 g / L, LNFPII in an amount of about 0.05 g / L to about 0.5 g / L, LNFP-I in an amount of about 0.2 g / L to about 2.0 g / L, and LNFP-II in an amount of about 0.2 g / L to about 2.0 g / L. an amount of LNFP-III, an amount of LND-I in an amount of about 0.2 g / L to about 2.0 g / L, an amount of MFLNH-III in an amount of about 0.2 g / L to about 2.0 g / L, an amount of LNFP-V in an amount of about 0.2 g / L to about 2.0 g / L, an amount of LNnDFH in an amount of about 0.2 g / L to about 2.0 g / L, and / or an amount of LNFP-VI in an amount of about 0.2 g / L to about 2.0 g / L.

[0018] The subject may be any suitable subject. The subject may be a human subject. In some embodiments, the subject is an infant, toddler, or young child. In preferred embodiments, the subject is an infant. In some embodiments, the subject is about 12 months or less, about 11 months or less, about 10 months or less, or about 9 months or less in age.

[0019] The one or more HMOs may improve the subject's social-emotional skills. The one or more HMOs may reduce the subject's negative affect. The subject's negative affect may be measured by the Infant Behavior Questionnaire (IBQ), e.g., the IBQ-Revised (IBQ-R). [Brief explanation of the drawings]

[0020] [Figure 1]Association between breastfeeding LNDFHI at 2 months and reduced infant negative affectivity at 9 months. A regression model approach was used to assess the association between breastfeeding LNDFHI and negative affectivity constructed from several Infant Temperament Questionnaire-Revised (IBQR) scales. N=195, p=0.0079. [Figure 2] Associations between 2'FL, 3FL, LDFT, and LNFP II in breast milk at 2 months and reduced negative affectivity at 9 months. A regression model approach was used to assess the associations between 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), and lacto-N-fucopentaose II (LNFP II) in breast milk and negative affectivity constructed from several Infant Temperament Questionnaire-Revised (IBQR) scales. N=195, p=0.026. [Figure 3] Association of 3FL in breast milk with (A) gross motor skills and (B) visual reception. Scatterplots of subjects' Mullen Scales of Early Learning (MSEL) subscale scores for gross motor (A) or visual reception (B) using breast milk 3FL levels. Using a linear mixed model approach, there was a significant association between 3FL in breast milk and infants' gross motor skills and visual reception MSEL subscale scores (N=170, p=0.041 and 0.027, respectively). To eliminate the potential confounding effect of age, age effects were removed from the HMO using smoothing spline regression before performing the associations. [Figure 4A]Associations of LNDFH-I, 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNDFH, and LNFP-VI in breast milk at 2 and 3 months with reduced negative affect at 9 months. Using a regression model approach, the associations of lacto-N-difucohexaose I (LNDFHI), 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), and lacto-N-fucopentaose II (LNFPII), LNFP-I (lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), and lacto-N-difucohexaose I (LND-I) were analyzed. The associations between lactoferrin-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI) and negative affectivity constructed from the Infant Temperament Questionnaire-Revised (IBQR) scale were assessed at 2 months (N=195, p=0.0056) and 3 months (N=195, p=0.0037), respectively. [Figure 4B]Associations of LNDFH-I, 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNDFH, and LNFP-VI in breast milk at 2 and 3 months with reduced negative affect at 9 months. Using a regression model approach, the associations of lacto-N-difucohexaose I (LNDFHI), 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), and lacto-N-fucopentaose II (LNFPII), LNFP-I (lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), and lacto-N-difucohexaose I (LND-I) were analyzed. The associations between lactoferrin-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI) and negative affectivity constructed from the Infant Temperament Questionnaire-Revised (IBQR) scale were assessed at 2 months (N=195, p=0.0056) and 3 months (N=195, p=0.0037), respectively. DETAILED DESCRIPTION OF THE INVENTION

[0021] Various preferred features and embodiments of the present invention will now be described by way of non-limiting example, it being understood that those skilled in the art can combine all features of the invention disclosed herein without departing from the scope of the invention as disclosed.

[0022] Any reference herein to a prior art document should not be taken as an acknowledgement that such prior art is well known or forms part of the common general understanding in the art. All publications mentioned herein are incorporated herein by reference.

[0023] As used herein, the words "comprises," "comprising," and similar words should not be construed in an exclusive or exhaustive sense. In other words, they mean "including, but not limited to." The terms "comprises," "comprising," and the like also include the term "consisting of."

[0024] The practice of the present invention will employ conventional techniques that are within the capabilities of those skilled in the art, unless otherwise indicated. Such techniques are explained in the literature. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0025] Numerical ranges are inclusive of the numbers defining the range, and all percentages disclosed herein are on a weight / weight basis unless otherwise specified. As used herein, the term "about" means approximately, in the region of, roughly, or in the vicinity of. When the term "about" is used in conjunction with a numerical value or range, that value or range modifies that value or range by expanding the upper and lower boundaries of the stated numerical value(s). In general, the terms "about" and "approximately" are used herein to adjust numerical values ​​10% above and below the stated value(s).

[0026] Human milk oligosaccharides (HMO) The present invention relates to the use of one or more human milk oligosaccharides (HMOs) to promote behavioral development, improve social and emotional skills, reduce negative emotions, and / or prevent anxiety and / or mood disorders. In some embodiments, one or more HMOs are used in a therapeutic method.

[0027] The one or more HMOs may be administered by any suitable route and in any suitable form. Preferably, the one or more HMOs are administered orally and / or enterally. In a preferred embodiment, the one or more HMOs are administered orally. The one or more HMOs may be administered separately, simultaneously, or sequentially. In a preferred embodiment, the one or more HMOs are administered simultaneously.

[0028] Many types of HMOs exist in human milk, and they are typically based on combinations of glucose, galactose, sialic acid (N-acetylneuraminic acid), fucose, and / or N-acetylglucosamine, with numerous and diverse linkages between them. Almost all HMOs have a lactose moiety at the reducing end, and sialic acid and / or fucose (if present) occupy the terminal positions of the non-reducing end. HMOs can be acidic (e.g., charged sialic acid-containing oligosaccharides) or neutral (e.g., fucosyl oligosaccharides). See, e.g., Chen, X., 2015. Advances in carbohydrate chemistry and biochemistry, 72, pp. 113-190.

[0029] HMOs present in human milk include lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-difucohexaose I (LNDFHI), lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose II (LNFP-II), lacto-N-fucopentaose III (LNFP-III), trifucosyllacto-N-hexaose (TF-LNH), 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), disialyllacto-N-tetraose (DSLNT), and sialyllacto-N-neotetraose c (LST). c) and fucosyldisialyllacto-N-hexaose I (FDS-LNH-I). See, for example, Soyyilmaz, B., et al., 2021. Nutrients, 13(8), p. 2737.

[0030] In some embodiments, the one or more HMOs comprise or consist of: (a) lacto-N-difucohexaose I (LNDFHI); or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

[0031] A subject may be administered any suitable amount of one or more HMOs, in any suitable form, and via any suitable route of administration (e.g., in any form and via any route described herein).

[0032] Suitable doses of HMOs are described, for example, in EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), 2022. EFSA Journal, 20(5), p. e07257; EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), 2021. EFSA Journal, 19(6), p. e06662; and EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), 2022. EFSA Journal, 20(3), p. e07140.

[0033] Preferably, the one or more HMOs are administered to the subject in a total amount of at least about 0.5 g / day, at least about 1 g / day, or at least about 2 g / day. Preferably, the one or more HMOs are administered to the subject in an amount of about 10 g / day or less, about 8 g / day or less, or about 5 g / day or less. Preferably, the one or more HMOs are administered to the subject in an amount of about 0.5 g / day to about 10 g / day, about 1 g / day to about 8 g / day, or about 2 g / day to about 5 g / day.

[0034] HMOs can be obtained by any suitable method. Suitable methods for synthesizing HMOs are well known to those skilled in the art. For example, processes have been developed for producing oligosaccharides by microbial fermentation, enzymatic processes, chemical synthesis, or a combination of these techniques (see, for example, Zeuner et al., 2019. Molecules, 24(11), p.2033).

[0035] Fucosylated HMOs In some embodiments, the one or more HMOs comprise or consist of a combination of fucosylated HMOs. In some embodiments, the one or more HMOs consist of a fucosylated HMO. In some embodiments, the one or more HMOs are fucosylated HMOs.

[0036] As used herein, fucosylated HMOs may refer to neutral HMOs containing one or more fucose sugars. Fucosylated HMOs may be monofucosylated, difucosylated, or trifucosylated, and preferably do not contain sialic acid. Non-limiting examples of fucosylated HMOs include 2'-fucosyllactose (2'FL); 3-fucosyllactose (3FL); lactodifucotetraose (LDFT); lacto-N-fucopentaose, such as lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose II (LNFP-II), lacto-N-fucopentaose III (LNFP-III), or lacto-N-fucopentaose V (LNFP-V); lacto-N-fucohexaose, such as For example, lacto-N-difucohexaose I (LNDFH-I) and lacto-N-difucohexaose II (LNDFH-II); lacto-N-neofucopentaose V (LNnFP-V); lacto-N-neodifucosylhexaose (LNnDFH), for example, lacto-N-neodifucosylhexaose II (LNnDFH-II); fucosyllacto-N-hexaose (FLNH), for example, fucosyllacto-N-hexaose I (FLNH-I) and fucosyllacto-N-hexaose Fucosyl lacto-N-neohexaose II (FLNH-II); fucosyl lacto-N-neohexaose (F-LNnH), e.g., fucosyl lacto-N-neohexaose I (F-LNnH-I) and fucosyl lacto-N-neohexaose II (F-LNnH-II); monofucosyl lacto-N-hexaose-III (MFNLH-III); difucosyl lacto-N-hexaose (LNH); difucosyl lacto-N-neohexaose (DF-LNnH), e.g., difucosyl lacto-N-neohexaose Examples of fucosyl lacto-N-neohexaose include difucosyl lacto-N-neohexaose I (DF-LNnH-I) and difucosyl lacto-N-neohexaose II (DF-LNnH-II); difucosyl lacto-N-hexaose-a (DFLNHa); trifucosyl lacto-N-hexaose (TF-LNH); fucosyl-para-lacto-N-hexaose (F-pLNH); difucosyl-para-lacto-N-hexaose (DF-pLNH); trifucosyl-para-lacto-N-hexaose (TF-pLNH); and combinations thereof.See, for example, Chen, X., 2015. Advances in carbohydrate chemistry and biochemistry, 72, pp. 113-190.

[0037] In some embodiments, the combination of fucosylated HMOs comprises or consists of lacto-N-difucohexaose I (LNDFHI), 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), and / or lacto-N-fucopentaose II (LNFPII). In some embodiments, the combination of fucosylated HMOs comprises or consists of lacto-N-difucohexaose I (LNDFHI), 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

[0038] In some embodiments, the combination of fucosylated HMOs comprises and / or consists of 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and / or lacto-N-fucopentaose VI (LNFP-VI). In some embodiments, the combination of fucosylated HMOs comprises or consists of 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

[0039] Preferably, the combination of fucosylated HMOs is administered to the subject in a total amount of at least about 0.5 g / day, at least about 1 g / day, or at least about 2 g / day. Preferably, the combination of fucosylated HMOs is administered to the subject in an amount of about 10 g / day or less, about 8 g / day or less, or about 5 g / day or less. Preferably, the combination of fucosylated HMOs is administered to the subject in an amount of about 0.5 g / day to about 10 g / day, about 1 g / day to about 8 g / day, or about 2 g / day to about 5 g / day.

[0040] Lacto-N-difucohexaose I (LNDFHI) In some embodiments, one or more HMOs comprise or consist of lacto-N-difucohexaose (LNDFHI). In some embodiments, one or more HMOs consist of LNDFHI. In some embodiments, one or more HMOs are LNDFHI.

[0041] Lacto-N-difucohexaose I (LNDFHI), also known as LNDFH-I or LNDI, is a difucosylated, non-sialylated Galβ1-3GlcNAc core human milk oligosaccharide that can have the following structure: [ka] During the ceremony, [ka] is fucose (Fuc), [ka] is galactose, [ka] is glucose, [ka] is N-acetylglucosamine (GlcNAc).

[0042] Preferably, LNDFHI is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.15 g / day, or at least about 0.2 g / day, or at least about 0.5 g / day. Preferably, LNDFHI is administered to a subject in an amount of about 5 g / day or less, about 4 g / day or less, about 3 g / day or less, about 2 g / day or less, or about 1 g / day or less. Preferably, LNDFHI is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.15 g / day to about 4 g / day, about 0.2 g / day to about 3 g / day, or about 0.5 g / day to about 2 g / day.

[0043] 2'-Fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

[0044] In some embodiments, the one or more HMOs comprise or consist of 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI). In some embodiments, the one or more HMOs consist of 2'FL, 3FL, LDFT, LNFPII, lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI). In some embodiments, the one or more HMOs are 2'FL, 3FL, LDFT, LNFPII, lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

[0045] 2'-Fucosyllactose (2'-FL) is a fucosylated neutral trisaccharide composed of L-fucose, D-galactose, and D-glucose units. 2'-FL is the most common HMO naturally occurring in human breast milk, constituting approximately 30% of all HMOs, and can have the following structure: [ka] During the ceremony, [ka] is fucose (Fuc), [ka] is galactose, [ka] is glucose.

[0046] 3-Fucosyllactose (3-FL) is a fucosylated neutral trisaccharide composed of an L-fucose unit, a D-galactose unit, and a D-glucose unit and can have the following structure: [ka] During the ceremony, [ka] is fucose (Fuc), [ka] is galactose, [ka] is glucose.

[0047] Lactodifucotetraose (LDFT), also known as difucosyllactose (diFL or DFL), can have the following structure: [ka] During the ceremony, [ka] is fucose (Fuc), [ka] is galactose, [ka] is glucose.

[0048] Lacto-N-fucopentaose II (LNFPII) is a fucosylated, non-sialylated Galβ1-3GlcNAc core (type 1 core) human milk oligosaccharide and may have the following structure: [ka] During the ceremony, [ka] is fucose (Fuc), [ka] is galactose, [ka] is glucose, [ka] is N-acetylglucosamine (GlcNAc).

[0049] The combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI may be administered separately, simultaneously, or sequentially. In a preferred embodiment, the combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI is administered simultaneously.

[0050] Preferably, 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI are administered to the subject in a total amount of at least about 0.5 g / day, at least about 1 g / day, or at least about 2 g / day. Preferably, 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI are administered to the subject in a total amount of no more than about 10 g / day, no more than about 8 g / day, or no more than about 5 g / day. Preferably, 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI are administered to a subject in a total amount of about 0.5 g / day to about 10 g / day, about 1 g / day to about 8 g / day, or about 2 g / day to about 5 g / day.

[0051] Preferably, 2'FL is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.2 g / day, at least about 0.3 g / day, at least about 0.4 g / day, at least about 0.5 g / day, at least about 0.8 g / day, or at least about 1 g / day. Preferably, 2'FL is administered to a subject in an amount of about 5 g / day or less, about 4 g / day or less, or about 3 g / day or less. Preferably, 2'FL is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.5 g / day to about 5 g / day, about 0.8 g / day to about 4 g / day, or about 1 g / day to about 3 g / day.

[0052] Preferably, 3FL is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.15 g / day, or at least about 0.2 g / day, or at least about 0.5 g / day. Preferably, 3FL is administered to a subject in an amount of about 5 g / day or less, about 4 g / day or less, about 3 g / day or less, about 2 g / day or less, or about 1 g / day or less. Preferably, 3FL is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.15 g / day to about 4 g / day, about 0.2 g / day to about 3 g / day, or about 0.5 g / day to about 2 g / day.

[0053] Preferably, LDFT is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.15 g / day, or at least about 0.2 g / day. Preferably, LDFT is administered to a subject in an amount of about 5 g / day or less, about 1 g / day or less, about 0.8 g / day or less, or about 0.6 g / day or less. Preferably, LDFT is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.1 g / day to about 1 g / day, about 0.15 g / day to about 0.8 g / day, or about 0.2 g / day to about 0.6 g / day.

[0054] Preferably, LNFPII is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.15 g / day, or at least about 0.2 g / day. Preferably, LNFPII is administered to a subject in an amount of about 5 g / day or less, about 1 g / day or less, about 0.8 g / day or less, or about 0.6 g / day or less. Preferably, LNFPII is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.1 g / day to about 1 g / day, about 0.15 g / day to about 0.8 g / day, or about 0.2 g / day to about 0.6 g / day.

[0055] Preferably, LNFP-I is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.15 g / day, or at least about 0.2 g / day. Preferably, LNFP-I is administered to a subject in an amount of about 5 g / day or less, about 1 g / day or less, about 0.8 g / day or less, or about 0.6 g / day or less. Preferably, LNFP-I is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.1 g / day to about 1 g / day, about 0.15 g / day to about 0.8 g / day, or about 0.2 g / day to about 0.6 g / day.

[0056] Preferably, LNFP-III is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.15 g / day, or at least about 0.2 g / day. Preferably, LNFP-III is administered to a subject in an amount of about 5 g / day or less, about 1 g / day or less, about 0.8 g / day or less, or about 0.6 g / day or less. Preferably, LNFP-III is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.1 g / day to about 1 g / day, about 0.15 g / day to about 0.8 g / day, or about 0.2 g / day to about 0.6 g / day.

[0057] Preferably, LND-I is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.15 g / day, or at least about 0.2 g / day. Preferably, LND-I is administered to a subject in an amount of about 5 g / day or less, about 1 g / day or less, about 0.8 g / day or less, or about 0.6 g / day or less. Preferably, LND-I is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.1 g / day to about 1 g / day, about 0.15 g / day to about 0.8 g / day, or about 0.2 g / day to about 0.6 g / day.

[0058] Preferably, MFLNH-III is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.15 g / day, or at least about 0.2 g / day. Preferably, MFLNH-III is administered to a subject in an amount of about 5 g / day or less, about 1 g / day or less, about 0.8 g / day or less, or about 0.6 g / day or less. Preferably, MFLNH-III is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.1 g / day to about 1 g / day, about 0.15 g / day to about 0.8 g / day, or about 0.2 g / day to about 0.6 g / day.

[0059] Preferably, LNFP-V is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.15 g / day, or at least about 0.2 g / day. Preferably, LNFP-V is administered to a subject in an amount of about 5 g / day or less, about 1 g / day or less, about 0.8 g / day or less, or about 0.6 g / day or less. Preferably, LNFP-V is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.1 g / day to about 1 g / day, about 0.15 g / day to about 0.8 g / day, or about 0.2 g / day to about 0.6 g / day.

[0060] Preferably, LNnDFH is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.15 g / day, or at least about 0.2 g / day. Preferably, LNnDFH is administered to a subject in an amount of about 5 g / day or less, about 1 g / day or less, about 0.8 g / day or less, or about 0.6 g / day or less. Preferably, LNnDFH is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.1 g / day to about 1 g / day, about 0.15 g / day to about 0.8 g / day, or about 0.2 g / day to about 0.6 g / day.

[0061] Preferably, LNFP-VI is administered to a subject in an amount of at least about 0.1 g / day, at least about 0.15 g / day, or at least about 0.2 g / day. Preferably, LNFP-VI is administered to a subject in an amount of about 5 g / day or less, about 1 g / day or less, about 0.8 g / day or less, or about 0.6 g / day or less. Preferably, LNFP-VI is administered to a subject in an amount of about 0.1 g / day to about 5 g / day, about 0.1 g / day to about 1 g / day, about 0.15 g / day to about 0.8 g / day, or about 0.2 g / day to about 0.6 g / day.

[0062] Nutritional Composition Suitably, the one or more HMOs are in the form of a composition, which may contain the one or more HMOs in any effective amount.

[0063] In one aspect, the present invention provides a composition (e.g., a nutritional composition, such as an infant formula, follow-on formula, or growing-up milk) comprising one or more human milk oligosaccharides (HMOs) for use in supporting behavioral development, improving social and emotional skills, reducing negative emotions, and / or preventing anxiety and / or mood disorders.

[0064] In another aspect, the present invention provides the use of one or more human milk oligosaccharides (HMOs) for the manufacture of a composition (e.g., a nutritional composition, such as an infant formula, follow-on formula, or growing-up milk) for supporting behavioral development, improving social and emotional skills, reducing negative emotions, and / or preventing anxiety and / or mood disorders.

[0065] In another aspect, the present invention provides a method for supporting behavioral development, improving social and emotional skills, reducing negative emotions, and / or preventing anxiety and / or mood disorders, comprising administering a composition (e.g., a nutritional composition, such as an infant formula, follow-on formula, or growing-up milk) comprising one or more human milk oligosaccharides (HMOs).

[0066] The composition may be any type of composition that can incorporate one or more HMOs, such as a composition in the form of a food or beverage product, a dietary supplement, or a pharmaceutical composition. The composition may be in the form of a solid (e.g., powder), liquid, or semi-liquid. The one or more HMOs may be in the form of a food composition, a beverage, a nutritional formula, a dietary supplement, a nutraceutical, or a pharmaceutical composition.

[0067] Food and beverage products include all products intended for oral consumption by humans for the purpose of providing nutrition and / or pleasure. For example, the composition may be a food or beverage product, such as a product for infants, toddlers, and / or young children. Examples of food and beverage products include dairy products, such as milk products or yogurt, soups, sauces, sweet and savory snacks, powdered drinks, and cereal products.

[0068] In some embodiments, the one or more HMOs are in the form of a nutritional composition, a medical food product for clinical nutrition, or a supplement.

[0069] In some embodiments, one or more HMOs are in the form of a nutritional composition. As used herein, "nutritional composition" can refer to a composition that provides nutrition to a subject. This nutritional composition is usually administered orally or intravenously and typically includes a lipid or fat source and a protein source.

[0070] The nutritional composition may be a synthetic nutritional composition. As used herein, "synthetic nutritional composition" may mean a nutritional composition obtained by chemical and / or biological means, which may be substantially chemically identical to a naturally occurring composition.

[0071] In some embodiments, the one or more HMOs are in the form of a medical food product for clinical nutrition. As used herein, "medical food product for clinical nutrition," also known as a "food for special medical purposes (FSMP)," refers to a specialized food designed to help meet the nutritional or dietary needs of subjects living with a disease, disorder, or medical condition that makes it impossible, temporarily or permanently, to achieve adequate nutritional intake from normal foods or through modification of a normal diet.

[0072] In some embodiments, the one or more HMOs are in the form of an infant formula, a follow-on formula, or a growing-up milk.

[0073] In some embodiments, the one or more HMOs are in the form of an infant formula. As used herein, the term "infant formula" refers to a food product intended for specific nutritional supplementation of infants during the first month of life, which by itself meets the nutritional requirements of infants falling within this category (e.g., Article 2(c) of the European Commission Directive 91 / 321 / EEC 2006 / 141 / EC of 22 December 2006, relating to infant formulas and follow-on formulas). The term also refers to nutritional compositions intended for infants, as defined in Codex Alimentarius (Codex STAN72-1981), and special infant foods (including foods for special medical purposes). The infant formula may be a preterm infant formula, a human milk fortifier, a starter infant formula, a follow-on formula, a baby food formula, or an infant cereal formula.

[0074] In some embodiments, the one or more HMOs are in the form of a starter infant formula. Typically, a "starter infant formula" is intended to be a breast milk substitute for an infant from the newborn stage onwards.

[0075] In some embodiments, the one or more HMOs are in the form of a follow-on formula. A "follow-up formula" or "follow-on formula" may be given from month 6 onwards. This formula may constitute the primary liquid component of an increasingly diverse diet for individuals in this category.

[0076] In some embodiments, the one or more HMOs are in the form of a preterm formula. As used herein, the term "preterm formula" refers to an infant formula intended for preterm infants.

[0077] In some embodiments, the one or more HMOs are in the form of a milk fortifier. As used herein, the term "milk fortifier" refers to a liquid or solid nutritional composition suitable for mixing with breast milk (or human milk, in the case of human milk fortifiers) or infant formula. Fortifiers are used to increase the calories, protein, minerals, and vitamins in breast milk given to preterm or low birth weight infants. The term "breast milk" should be understood as mother's milk or mother's colostrum, or donor's milk or the colostrum of donor's milk.

[0078] In some embodiments, the one or more HMOs are in the form of a baby food formula. As used herein, the term "baby food formula" refers to a food product intended for specific nutritional use by infants or children, e.g., young children, during the first year of life.

[0079] In some embodiments, the one or more HMOs are in the form of growing-up milk. As used herein, the term "growing-up milk" (or GUM) refers to a milk formula product fed from age 1 onwards. GUMs are generally dairy-based drinks adapted to the specific nutritional needs of young children (e.g., children from about 1 to about 3 years of age). Growing-up milk is also known as "young child formula" or "infant milk".

[0080] In some embodiments, the one or more HMOs are in the form of an infant cereal composition. As used herein, the term "infant cereal composition" refers to a food product intended for specific nutritional use by an infant or child, e.g., a young child, during the first year of life.

[0081] In some embodiments, the one or more HMOs are in the form of a milk formula. As used herein, the term "milk formula" may refer to, for example, a food product intended for childhood nutrition, which may provide a sole or supplemental source of nutrition for, for example, children aged about 3 years or older. In some embodiments, the milk formula is GrowMilk.

[0082] In some embodiments, the composition is in powder form and is reconstituted with an aqueous medium (e.g., water) prior to administration, while in other embodiments, the composition is in liquid form ready for administration (e.g., a ready-to-feed formula).

[0083] In another embodiment, one or more HMOs are in the form of a supplement. As used herein, "supplement" or "dietary supplement" can be used to supplement a subject's nutrition (and is typically used as such, but dietary supplements can also be added to any type of composition intended for ingestion by a subject). When the composition is a supplement, such a composition can be provided in the form of a unit dose. Supplements typically exist in the form of liquids, gels, powders, or tablets or capsules. Powder supplements typically include supplements that are to be dissolved in water or milk, or sprinkled on food or beverages. Such supplements are intended to provide additional nutritional and / or health benefits to the subject who takes the supplement. Supplements can be used to provide nutritional and / or health benefits to humans and animals.

[0084] In another embodiment, the one or more HMOs are in the form of a fortifier. The fortifier may be an infant formula fortifier or a growing-up milk fortifier.

[0085] In another embodiment, the one or more HMOs are in the form of a pharmaceutical product, such as a drop, syrup, powder, tablet, or capsule product intended to treat or prevent an adverse medical condition in a subject in need thereof.

[0086] Human milk oligosaccharides (HMO) The one or more HMOs can be present in the composition in any suitable amount.

[0087] For example, in infant formula, follow-on formula, or growing-up milk, a person skilled in the art may base the amount of HMO on the amount present in human breast milk produced for an infant or child of the same age, particularly produced by a nutritionally replete mother (see, e.g., Soyyilmaz, B., et al., 2021. Nutrients, 13(8), p. 2737). Such amounts may be within the following ranges in human breast milk: LNDFHI: about 0.2 g / L to about 2.0 g / L; 2'FL: about 0.5 g / L to about 3.0 g / L; 3FL: about 0.2 g / L to about 2.0 g / L; LDFT: about 0.1 g / L to about 0.1 g / L; and LNFPII: about 0.1 g / L to about 1.0 g / L. However, the amounts may fall outside this range depending, for example, on the bioavailability of the HMO from infant formula compared to human breast milk.

[0088] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises one or more HMOs in a total amount of at least about 0.1 g / L, at least about 0.2 g / L, or at least about 0.5 g / L. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises one or more HMOs in a total amount of no more than about 10.0 g / L, no more than about 8.0 g / L, or no more than about 5.0 g / L. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises one or more HMOs in a total amount of from about 0.1 g / L to about 10.0 g / L, from about 0.2 g / L to about 8.0 g / L, or from about 0.5 g / L to about 5.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0089] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises one or more HMOs in a total amount of at least about 0.5%, at least about 1%, or at least about 2% by weight on a dry weight basis. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises one or more HMOs in a total amount of no more than about 10%, no more than about 8%, or no more than about 5% by weight on a dry weight basis. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises one or more HMOs in a total amount of about 0.5% to about 10%, about 1% to about 8%, or about 2% to about 5% by weight on a dry weight basis.

[0090] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises a combination of fucosylated HMOs in a total amount of at least about 0.1 g / L, at least about 0.2 g / L, or at least about 0.5 g / L. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises a combination of fucosylated HMOs in a total amount of no more than about 10.0 g / L, no more than about 8.0 g / L, or no more than about 5.0 g / L. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises a combination of fucosylated HMOs in a total amount of about 0.1 g / L to about 10.0 g / L, about 0.2 g / L to about 8.0 g / L, or about 0.5 g / L to about 5.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0091] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises a combination of fucosylated HMOs in a total amount of at least about 0.5%, at least about 1%, or at least about 2% by weight on a dry weight basis. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises a combination of fucosylated HMOs in a total amount of no more than about 10%, no more than about 8%, or no more than about 5% by weight on a dry weight basis. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises a combination of fucosylated HMOs in a total amount of about 0.5% to about 10%, about 1% to about 8%, or about 2% to about 5% by weight on a dry weight basis.

[0092] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNDFHI in an amount of at least about 0.1 g / L, at least about 0.15 g / L, or at least about 0.2 g / L. Preferably, the nutritional composition comprises LNDFHI in an amount of about 3.0 g / L or less, about 2.5 g / L or less, or about 2.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNDFHI in an amount of about 0.1 g / L to about 3.0 g / L, about 0.15 g / L to about 2.5 g / L, or about 0.2 g / L to about 2.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0093] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises 2'FL in an amount of at least about 0.1 g / L, at least about 0.2 g / L, or at least about 0.5 g / L. Preferably, the nutritional composition comprises 2'FL in an amount of about 5.0 g / L or less, about 4.0 g / L or less, or about 3.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises 2'FL in an amount of about 0.1 g / L to about 5.0 g / L, about 0.2 g / L to about 4.0 g / L, or about 0.5 g / L to about 3.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0094] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises 3FL in an amount of at least about 0.1 g / L, at least about 0.15 g / L, or at least about 0.2 g / L. Preferably, the nutritional composition comprises 3FL in an amount of about 3.0 g / L or less, about 2.5 g / L or less, or about 2.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises 3FL in an amount of about 0.1 g / L to about 3.0 g / L, about 0.15 g / L to about 2.5 g / L, or about 0.2 g / L to about 2.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0095] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LDFT in an amount of at least about 0.05 g / L, at least about 0.08 g / L, or at least about 0.1 g / L. Preferably, the nutritional composition comprises LDFT in an amount of about 2.0 g / L or less, about 1.5 g / L or less, or about 1.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LDFT in an amount of about 0.05 g / L to about 2.0 g / L, about 0.08 g / L to about 1.5 g / L, or about 0.1 g / L to about 1.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0096] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNFPII in an amount of at least about 0.05 g / L, at least about 0.08 g / L, or at least about 0.1 g / L. Preferably, the nutritional composition comprises LNFPII in an amount of about 2.0 g / L or less, about 1.5 g / L or less, or about 1.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNFPII in an amount of about 0.05 g / L to about 2.0 g / L, about 0.08 g / L to about 1.5 g / L, or about 0.1 g / L to about 1.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0097] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNFP-I in an amount of at least about 0.05 g / L, at least about 0.08 g / L, or at least about 0.1 g / L. Preferably, the nutritional composition comprises LNFP-I in an amount of about 2.0 g / L or less, about 1.5 g / L or less, or about 1.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNFP-I in an amount of about 0.05 g / L to about 2.0 g / L, about 0.08 g / L to about 1.5 g / L, or about 0.1 g / L to about 1.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0098] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNFP-III in an amount of at least about 0.05 g / L, at least about 0.08 g / L, or at least about 0.1 g / L. Preferably, the nutritional composition comprises LNFP-III in an amount of about 2.0 g / L or less, about 1.5 g / L or less, or about 1.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNFP-III in an amount of about 0.05 g / L to about 2.0 g / L, about 0.08 g / L to about 1.5 g / L, or about 0.1 g / L to about 1.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0099] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LND-I in an amount of at least about 0.05 g / L, at least about 0.08 g / L, or at least about 0.1 g / L. Preferably, the nutritional composition comprises LND-I in an amount of about 2.0 g / L or less, about 1.5 g / L or less, or about 1.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LND-I in an amount of about 0.05 g / L to about 2.0 g / L, about 0.08 g / L to about 1.5 g / L, or about 0.1 g / L to about 1.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0100] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises MFLNH-III in an amount of at least about 0.05 g / L, at least about 0.08 g / L, or at least about 0.1 g / L. Preferably, the nutritional composition comprises MFLNH-III in an amount of about 2.0 g / L or less, about 1.5 g / L or less, or about 1.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises MFLNH-III in an amount of about 0.05 g / L to about 2.0 g / L, about 0.08 g / L to about 1.5 g / L, or about 0.1 g / L to about 1.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0101] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNFP-V in an amount of at least about 0.05 g / L, at least about 0.08 g / L, or at least about 0.1 g / L. Preferably, the nutritional composition comprises LNFP-V in an amount of about 2.0 g / L or less, about 1.5 g / L or less, or about 1.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNFP-V in an amount of about 0.05 g / L to about 2.0 g / L, about 0.08 g / L to about 1.5 g / L, or about 0.1 g / L to about 1.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0102] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNnDFH in an amount of at least about 0.05 g / L, at least about 0.08 g / L, or at least about 0.1 g / L. Preferably, the nutritional composition comprises LNnDFH in an amount of about 2.0 g / L or less, about 1.5 g / L or less, or about 1.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNnDFH in an amount of about 0.05 g / L to about 2.0 g / L, about 0.08 g / L to about 1.5 g / L, or about 0.1 g / L to about 1.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0103] Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNFP-VI in an amount of at least about 0.05 g / L, at least about 0.08 g / L, or at least about 0.1 g / L. Preferably, the nutritional composition comprises LNFP-VI in an amount of about 2.0 g / L or less, about 1.5 g / L or less, or about 1.0 g / L or less. Preferably, the nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) comprises LNFP-VI in an amount of about 0.05 g / L to about 2.0 g / L, about 0.08 g / L to about 1.5 g / L, or about 0.1 g / L to about 1.0 g / L. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0104] Other ingredients The nutritional compositions of the present invention (e.g., infant formula, follow-on formula, or growing-up milk) may contain a protein source, a carbohydrate source, and a lipid source. However, in some embodiments, particularly when the nutritional composition of the present invention is a supplement or fortifier, only lipid (or a lipid source) may be present.

[0105] Nutritional compositions of the present invention (e.g., infant formula, follow-on formula, or growing-up milk) may have a calorie content of about 50 kcal / 100 mL to about 90 kcal / 100 mL, about 55 kcal / 100 mL to about 85 kcal / 100 mL, about 60 kcal / 100 mL to about 80 kcal / 100 mL, about 65 kcal / 100 mL to about 75 kcal / 100 mL, or about 65 kcal / 100 mL to about 70 kcal / 100 mL. If the nutritional composition is in powder form, these amounts may be after reconstitution with a liquid according to the instructions provided.

[0106] The nutritional compositions of the present invention (e.g., infant formula, follow-on formula, or growing-up milk) may have, on a dry weight basis, about 100 kcal / 100g to about 1000 kcal / 100g, about 200 kcal / 100g to about 800 kcal / 100g, or about 400 kcal / 100g to about 600 kcal / 100g.

[0107] protein Nutritional compositions (e.g., infant formula, follow-on formula, or growing-up milk) according to the present invention may contain a protein source, which may be in an amount of about 1 g to about 4 g / 100 kcal, about 1.5 g to about 3 g / 100 kcal, or about 1.5 g to about 2.5 g / 100 kcal.

[0108] For example, protein sources based on whey, casein, and mixtures thereof can be used, as well as vegetable protein sources, such as soybean-based protein sources. With regard to whey protein, the protein source may be based on acid whey, sweet whey, or a mixture thereof, and may contain α-lactalbumin and β-lactoglobulin in any desired proportion. In some embodiments, the primary protein source is whey (i.e., more than 50%, e.g., more than 60% or more than 70% of the protein is derived from whey protein). The protein may be a native protein, a hydrolyzed protein, or a mixture of native and hydrolyzed proteins. The term "intact" means that the majority of the protein is in an intact state, i.e., the molecular structure is unchanged, e.g., at least 80% of the protein is unchanged, e.g., at least 85% of the protein is unchanged, preferably at least 90% of the protein is unchanged, and even more preferably, at least 95% of the protein is unchanged, e.g., at least 98% of the protein is unchanged. In certain embodiments, the protein is completely unchanged.

[0109] The term "hydrolyzed" in the context of the present invention means that a protein has been hydrolyzed or broken down into its constituent amino acids.

[0110] Protein can be either completely hydrolyzed or partially hydrolyzed.When hydrolyzed protein is required, the hydrolysis process can be carried out as desired as known in the art.For example, whey protein hydrolysate can be prepared by enzymatically hydrolyzing whey fraction in one or more steps.It has been found that if the whey fraction used as starting material is substantially lactose-free, the lysine blackage that the protein undergoes during the hydrolysis process is significantly reduced.This can reduce the degree of lysine blackening from about 15% by weight of total lysine to less than about 10% by weight, for example, about 7% by weight of lysine, which significantly improves the nutritional value of the protein source.

[0111] In a particular embodiment, the protein of the composition is hydrolyzed, fully hydrolyzed, or partially hydrolyzed. The degree of hydrolysis (DH) of the protein may be between 2 and 20, or between 8 and 40, or between 20 and 60, or between 20 and 80, or greater than 10, greater than 20, greater than 40, greater than 60, greater than 80, or greater than 90.

[0112] At least 70%, 80%, 85%, 90%, 95%, or 97% of the protein may be hydrolyzed, hi certain embodiments, 100% of the protein is hydrolyzed.

[0113] In one particular embodiment, the protein of the composition is a vegetable protein.

[0114] carbohydrates Nutritional compositions (e.g., infant formula, follow-on formula, or growing-up milk) according to the present invention may contain a carbohydrate source, which may be in an amount of about 5 g to about 20 g / 100 kcal, about 10 g to about 15 g / 100 kcal, or about 8 g to about 15 g / 100 kcal.

[0115] Although any carbohydrate source commonly found in nutritional compositions may be used, such as lactose, sucrose, saccharose, maltodextrin, starch, and mixtures thereof, one preferred carbohydrate source is lactose.

[0116] lipids Nutritional compositions (e.g., infant formula, follow-on formula, or growing-up milk) according to the present invention may contain lipids and essential fatty acids. The lipids may be in an amount of about 1 g to about 10 g / 100 kcal, about 2 g to about 8 g / 100 kcal, or about 3 g to about 8 g / 100 kcal.

[0117] Non-limiting examples of lipids include palm olein, high oleic sunflower oil, high oleic safflower oil, canola oil, fish oil, coconut oil, milk fat, and combinations thereof. The composition may be particularly beneficial if it contains fat in an amount of about 25 to about 30 g / 100 g of dry weight of the composition. Non-limiting examples of essential fatty acids include linoleic acid (LA) and alpha-linolenic acid (ALA). The compositions of the present invention may further contain gangliosides, monosialoganglioside-3 (GM3) and disialoganglioside-3 (GD3), and combinations thereof.

[0118] others The nutritional compositions of the present invention (e.g., infant formula, follow-on formula, or growing-up milk) may also contain nutritionally relevant amounts of all vitamins and minerals considered essential for a daily diet. Minimum required amounts have been established for certain vitamins and minerals. Examples of minerals, vitamins, and other nutrients optionally present in the compositions of the present invention include vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, vitamin E, vitamin K1, vitamin K2, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorus, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum, taurine, and L-carnitine. Minerals are usually added in salt form. The presence and amount of specific minerals and other vitamins will vary depending on the target population.

[0119] If desired, the nutritional compositions of the present invention (e.g., infant formula, follow-on formula, or growing-up milk) may contain emulsifiers and stabilizers, such as soy, lecithin, citrate esters of mono- and diglycerides, and the like.

[0120] Preparation of the Composition The composition according to the present invention can be prepared by any known or other suitable method. For example, a nutritional composition (e.g., infant formula, follow-on formula, or growing-up milk) can be prepared by blending a protein source, a carbohydrate source, and a fat source together in appropriate proportions. If used, an emulsifier can be included at this point. Vitamins and minerals can be added at this point, but can also be added later, usually to avoid thermal degradation. Water, preferably reverse osmosis treated water or deionized water, can then be added and mixed to form a liquid mixture. The temperature of the mixture is preferably room temperature, but can also be higher. The liquid mixture can then be heat-treated to reduce bacterial content. The mixture can then be homogenized.

[0121] If it is desired to produce a powdered composition, the homogenized mixture is dried in suitable drying equipment, such as a spray dryer or freeze dryer, to form a powder.

[0122] The processes used in formula manufacturing are based on the concept that products must be nutritionally adequate and microbiologically safe for consumption. Therefore, steps that eliminate or limit microbial growth are central to the manufacturing process. While the processing techniques for each specific formula are proprietary to the manufacturer, they generally involve preserving an oil-in-water (o / w) emulsion by dehydration in the case of powdered products, or sterilization in the case of ready-to-feed or concentrated liquid products. Powdered formulas can be produced using a variety of processes, such as dry-blending dehydrated ingredients to form a homogeneous formula, or hydrating and wet-blending a mixture of macroingredients, such as fat, protein, and carbohydrate ingredients, followed by evaporation and spray-drying the resulting mixture. A combination of the two processes may also be used, where a base powder is first produced by wet-blending and spray-drying all or some of the macroingredients, followed by dry-blending the remaining ingredients, including carbohydrates, minerals, vitamins, and other micronutrients, to create the final formula. Liquid formulas are available in ready-to-feed form or as concentrates that must usually be diluted 1:1 with water. The manufacturing processes used for these products are similar to those used to make recombined milk.

[0123] If it is desired to produce a liquid formula, the homogenized mixture may be filled, preferably aseptically, into a suitable container. However, liquid compositions may also be retorted in the container, and suitable equipment for this type of filling and retorting is commercially available.

[0124] How to support behavioral development One or more HMOs may be used to promote behavioral development.

[0125] The terms "support," "promote," "enhance," or "improve" may be used interchangeably in the context of the present invention. The terms should be understood to include supporting or assisting the normal development or growth of an individual. For example, one or more HMOs may be used to improve behavioral skills.

[0126] As used herein, "behavioral development" may refer to a subject's development in behavioral skills such as communication, empathy, and conflict resolution. In particular, the term "behavioral development" may refer to the development of social behavior or social cognition, such as empathic and prosocial behavior toward others, which allows a subject to cooperate with and learn more effectively from others (see, for example, Moore, C., Corbit K. 2019. Social cognition in infancy. Encyclopedia on Early Childhood Development). Suitable methods and parameters for measuring behavioral development are known to those skilled in the art (see, for example, Johnson, S. and Marlow, N., 2006. Early human development, 82(3), pp. 173-183).

[0127] As used herein, "supporting behavioral development" can refer to supporting normal behavioral development, for example, during infancy, childhood, and adolescence. Supporting behavioral development can result in normal behavioral skills.

[0128] In one aspect, the invention provides one or more HMOs for use in supporting behavioral development in a subject. In another aspect, the invention provides the use of one or more HMOs for supporting behavioral development in a subject. In another aspect, the invention provides a method of supporting behavioral development in a subject, the method comprising administering to the subject an effective amount of one or more HMOs.

[0129] In one aspect, the invention provides a combination of fucosylated HMOs for use in supporting behavioral development in a subject. In another aspect, the invention provides a use of a combination of fucosylated HMOs for supporting behavioral development in a subject. In another aspect, the invention provides a method of supporting behavioral development in a subject, the method comprising administering to the subject an effective amount of a combination of fucosylated HMOs.

[0130] In one aspect, the present invention provides LNDFHI for use in supporting behavioral development in a subject. In another aspect, the present invention provides use of LNDFHI for supporting behavioral development in a subject. In another aspect, the present invention provides a method of supporting behavioral development in a subject, the method comprising administering an effective amount of LNDFHI to the subject.

[0131] In one aspect, the present invention provides a combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI for use in supporting behavioral development in a subject. In another aspect, the present invention provides use of a combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI for supporting behavioral development in a subject. In another aspect, the present invention provides a method for supporting behavioral development in a subject, the method comprising administering to the subject an effective amount of a combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI.

[0132] How to Improve Social and Emotional Skills One or more HMOs may be used to improve social and emotional skills.

[0133] In one aspect, the present invention provides one or more HMOs for use in improving social-emotional skills in a subject. In another aspect, the present invention provides the use of one or more HMOs for improving social-emotional skills in a subject. In another aspect, the present invention provides a method for improving social-emotional skills in a subject, the method comprising administering to the subject an effective amount of one or more HMOs.

[0134] In one aspect, the present invention provides a fucosylated HMO combination for use in improving social and emotional skills in a subject. In another aspect, the present invention provides a use of a fucosylated HMO combination for improving social and emotional skills in a subject. In another aspect, the present invention provides a method for improving social and emotional skills in a subject, the method comprising administering to the subject an effective amount of a fucosylated HMO combination.

[0135] In one aspect, the present invention provides the LNDFHI for use in improving social-emotional skills in a subject. In another aspect, the present invention provides uses of the LNDFHI for improving social-emotional skills in a subject. In another aspect, the present invention provides a method for improving social-emotional skills in a subject, the method comprising administering an effective amount of the LNDFHI to the subject.

[0136] In one aspect, the present invention provides a combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI for use in improving social and emotional skills in a subject. In another aspect, the present invention provides a use of a combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI for improving social and emotional skills in a subject. In another aspect, the present invention provides a method for improving social and emotional skills in a subject, comprising administering to the subject an effective amount of a combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI.

[0137] As used herein, "improving social-emotional skills" may refer to, for example, supporting the development of normal social-emotional skills during infancy, childhood, and adolescence. Supporting social-emotional skills may result in normal social-emotional skills. In the context of the present invention, the terms "social-emotional" or "social-emotional development" may relate to social-emotional skills that develop after birth, enabling increased autonomy, self-regulation, and relationships. Social-emotional development can be behaviorally assessed and monitored using clinical interviews, direct behavioral observations, and rating systems, as well as parent- and teacher-rated questionnaires.

[0138] In some embodiments, social-emotional skills are measured by the Infant Temperament Questionnaire (IBQ), e.g., the IBQ-Revised (IBQ-R). The IBQ-R (Infant Temperament Questionnaire-Revised) questionnaire is a widely used parent-rated measure for assessing temperament dimensions in 3-12 month old infants along 14 scales, as reported below (see, e.g., Gartstein, MA and Rothbart, MK, 2003. Infant behavior and development, 26(1), pp. 64-86).

[0139] [Table 1]

[0140] In some embodiments, social-emotional skills are measured by the Toddler Behavior Assessment Questionnaire (TBAQ). The Toddler Temperament Questionnaire (TBAQ) is used to measure behavior in young children aged 16-36 months (Goldsmith, HH, 1996. Child Development, 67(1), pp. 218-235). The TBAQ includes 120 items and 11 scales: activity level, perceptual sensitivity, inhibitory control, soothingness, appropriate attention allocation, sadness, object fear, anger, social fear, contentment, and interest. Items are rated on a 7-point scale ranging from 1 = never to 4 = about half the time to 7 = all the time in the past month.

[0141] One or more HMOs may be used to improve social skills. In one embodiment, the present invention provides one or more HMOs for use in improving social skills in a subject. In another embodiment, the present invention provides the use of one or more HMOs for improving social skills in a subject. In another embodiment, the present invention provides a method for improving social skills in a subject, comprising administering an effective amount of one or more HMOs to the subject.

[0142] In the context of the present invention, "social skills" can encompass any ability or behavior observed in a social situation or environment and / or that facilitates interaction and communication with others, both verbally and non-verbally, and the development of social skills begins in the first few months of life. For example, infants begin to show clear facial expressions of emotions, such as happiness, anger, sadness, interest, fear, disgust, and surprise. Infants also begin to laugh and interact with people through babbling. Social skills continue to develop in infants and children, including, for example, beginning to imitate the environment at approximately 15 months of age, clinging to a caregiver in novel situations (social fear) at 18 months of age, and playing alongside other children at approximately 24 months of age.

[0143] One or more HMOs can also be used to promote emotional skills. In one aspect, the present invention provides one or more HMOs for use in improving emotional skills in a subject. In another aspect, the present invention provides the use of one or more HMOs for improving emotional skills in a subject. In another aspect, the present invention provides a method for improving emotional skills in a subject, comprising administering an effective amount of one or more HMOs to the subject.

[0144] In the context of the present invention, "emotional skills" may refer to the ability to experience and express personal feelings, as well as the ability to recognize and interpret the emotions of others. Emotional skills are related to, for example, mood, happiness, and sadness. The development of emotional skills occurs from birth through childhood, adolescence, and adulthood, along with neurological, cognitive, and behavioral development.

[0145] One or more HMOs according to the present invention may improve the social and emotional skills of subjects aged 9 months, 12 months, 18 months, 24 months, or 36 months. One or more HMOs according to the present invention may improve the social and emotional skills of subjects aged 9-36 months. One or more HMOs according to the present invention may improve the social and emotional skills of subjects aged 9 months.

[0146] How to reduce negative emotions One or more HMOs may also be used to reduce negative emotions.

[0147] In one aspect, the present invention provides one or more HMOs for use in reducing negative emotions in a subject. In another aspect, the present invention provides the use of one or more HMOs for reducing negative emotions in a subject. In another aspect, the present invention provides a method for reducing negative emotions in a subject, the method comprising administering to the subject an effective amount of one or more HMOs.

[0148] In one aspect, the present invention provides a fucosylated HMO combination for use in reducing negative emotions in a subject. In another aspect, the present invention provides a use of a fucosylated HMO combination for reducing negative emotions in a subject. In another aspect, the present invention provides a method for reducing negative emotions in a subject, the method comprising administering to the subject an effective amount of a fucosylated HMO combination.

[0149] In one aspect, the present invention provides LNDFHI for use in reducing negative emotions in a subject. In another aspect, the present invention provides use of LNDFHI for reducing negative emotions in a subject. In another aspect, the present invention provides a method for reducing negative emotions in a subject, the method comprising administering an effective amount of LNDFHI to the subject.

[0150] In one aspect, the present invention provides a combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI for use in reducing negative affect in a subject. In another aspect, the present invention provides use of a combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI for reducing negative affect in a subject. In another aspect, the present invention provides a method of reducing negative affect in a subject, comprising administering to the subject an effective amount of a combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI.

[0151] As used herein, "negative affect" may refer to a personality variable that includes experiencing negative emotions and low self-concept. Negative affect encompasses a wide range of negative mood states, including fear, anxiety, hostility, contempt, and disgust (see, for example, Watson, D., et al., 1988. Journal of abnormal psychology, 97(3), p. 346). Preferably, in the context of the present invention, the term "negative affect" may be used interchangeably with the term "negative emotion" or "negative mood state."

[0152] A subject's negative affect can be measured by any suitable method. In some embodiments, a subject's negative affect is measured by the Infant Temperament Questionnaire (IBQ), e.g., the IBQ-Revised (IBQ-R). For example, negative affect can be a domain comprised of the following scales of the IBQ-R: sadness, fear, negative emotional expression in response to restrictions, activity level, and reduced reactivity. One or more HMOs according to the present invention may reduce sadness, fear, and / or negative emotional expression in response to restrictions. One or more HMOs according to the present invention may improve activity level and / or ease of recovery from bad moods.

[0153] One or more HMOs according to the present invention may reduce negative affect in subjects aged 9 months, 12 months, 18 months, 24 months, or 36 months. One or more HMOs according to the present invention may reduce negative affect in subjects aged 9-36 months. One or more HMOs according to the present invention may reduce negative affect in subjects aged 9 months.

[0154] One or more HMOs may promote mood and joyful behavior. In the context of the present invention, the term "mood" may refer to an individual's emotional state at a particular time. In the context of the present invention, the term "joy" may refer to a sense of great contentment and happiness. Joy is a powerful antidote to stress, which has adverse effects during infant development. Persistent stressful events produce feelings of anxiety. Promoting joy can reduce feelings of anxiety. Promoting mood and joyful behavior in infants may reduce the risk of experiencing mood difficulties. Difficulty can lead to aggressive or disruptive behavior, feelings of loneliness, and can cause behavioral problems later in life. One or more HMOs may promote preference and enjoyment of strong stimuli in infants, particularly stimuli that are high in intensity, speed, complexity, novelty, and incongruity, and reduce sadness, particularly mood and decreased activity associated with suffering from a physical condition, loss of an object, or inability to perform an action.

[0155] One or more HMOs according to the present invention may promote mood and pleasure behavior in subjects aged 9 months, 12 months, 18 months, 24 months, or 36 months. One or more HMOs according to the present invention may promote mood and pleasure behavior in subjects aged 9-36 months. One or more HMOs according to the present invention may promote mood and pleasure behavior in subjects aged 9 months.

[0156] Methods for preventing anxiety or mood disorders One or more HMOs may be used to prevent anxiety and / or mood disorders.

[0157] In one aspect, the invention provides one or more HMOs for use in preventing an anxiety and / or mood disorder in a subject. In another aspect, the invention provides the use of one or more HMOs for preventing an anxiety and / or mood disorder in a subject. In another aspect, the invention provides a method for preventing an anxiety and / or mood disorder in a subject, the method comprising administering to the subject an effective amount of one or more HMOs.

[0158] In one aspect, the invention provides a fucosylated HMO combination for use in preventing an anxiety and / or mood disorder in a subject. In another aspect, the invention provides a use of a fucosylated HMO combination for preventing an anxiety and / or mood disorder in a subject. In another aspect, the invention provides a method for preventing an anxiety and / or mood disorder in a subject, the method comprising administering to the subject an effective amount of a fucosylated HMO combination.

[0159] In one aspect, the present invention provides LNDFHI for use in preventing an anxiety disorder and / or a mood disorder in a subject. In another aspect, the present invention provides use of LNDFHI for preventing an anxiety disorder and / or a mood disorder in a subject. In another aspect, the present invention provides a method for preventing an anxiety disorder and / or a mood disorder in a subject, the method comprising administering an effective amount of LNDFHI to the subject.

[0160] In one aspect, the present invention provides a combination of 2'FL, 3FL, LDFT LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI for use in preventing an anxiety disorder and / or a mood disorder in a subject. In another aspect, the present invention provides a use of a combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI for preventing an anxiety disorder and / or a mood disorder in a subject. In another aspect, the present invention provides a method for preventing an anxiety disorder and / or a mood disorder in a subject, the method comprising administering to the subject an effective amount of a combination of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI.

[0161] In the context of the present invention, "preventing" a disorder may refer to reducing the severity of the disorder, or alleviating symptoms induced by the disorder, such as stress, and / or reducing complications caused by the disorder. In the context of the present invention, "preventing" a disorder may also refer to reducing the risk of developing the disorder.

[0162] One or more HMOs may improve social interactions in infants, toddlers, or young children aged 12 months or older, such as play behavior and / or behavior in response to novelty and / or new situations and / or behavior toward new people and / or strangers. Improving social and emotional skills in infants, toddlers, and / or young children may reduce the risk of developing behavioral disorders, such as anxiety disorders or depressive disorders, later in life (see, e.g., Watson, D., et al., 1988, Journal of Abnormal Psychology, 97(3), p. 346). This potential improvement is due to the belief that lack of social skills can have undesirable consequences in children's development, such as interfering with their ability to form relationships, affecting their school adjustment, and causing feelings of loneliness, which may lead to behavioral problems later in life.

[0163] Examples of anxiety disorders include generalized anxiety disorder, social anxiety disorder (social phobia) and separation disorder. Generalized anxiety disorder, separation anxiety disorder and social phobia are the most common early-onset childhood psychiatric disorders and adult depression, and are thought to be lifelong comorbidities and reduced quality of life (see, for example, Copeland, WE, et al., 2009. Archives of general psychiatry, 66(7), pp.764-772).

[0164] Mood disorders are a group of mental disorders, including, for example, bipolar disorder and depressive disorder. Mood is defined as a pervasive and persistent feeling that persists internally and affects almost all aspects of a person's behavior in the external world. Mood disorders are described by significant disturbances of affect (severe depression, called depression, or elation, called severe mania or mania). Mood disorders include bipolar disorder, cyclothymia, hypomania, major depressive disorder, disruptive mood dysregulation, persistent depressive disorder, and premenstrual dysphoric disorder.

[0165] Methods for supporting gross motor skills and visual reception One or more HMOs may be used to support gross motor skills and visual reception.

[0166] In some embodiments, the present invention provides 3FL for use in supporting gross motor skills and visual reception in a subject. In another embodiment, the present invention provides the use of 3FL for supporting gross motor skills and visual reception in a subject. In another embodiment, the present invention provides a method for supporting gross motor skills and visual reception in a subject, comprising administering an effective amount of 3FL to the subject.

[0167] In some embodiments, gross motor skills and visual reception are measured using scores on the Mullen Scales of Early Learning (MSEL), a validated and widely used assessment tool for infant cognitive development that includes five domains: fine motor, gross motor, visual reception, receptive language, and expressive language (Mullen EM. Mullen scales of early learning. AGS Circle Pines, MN; 1995).

[0168] subject The subject may be any suitable subject. Preferably, the subject may be a human.

[0169] In preferred embodiments, the subject is an infant, toddler, or young child. The term "infant" can refer to a subject between about 0 and about 1 year of age. The term "toddler" can refer to a subject between about 1 and about 3 years of age. The term "young child" can refer to a subject between about 3 and about 10 years of age, between about 3 and about 9 years of age, between about 3 and about 8 years of age, between about 3 and about 7 years of age, between about 3 and about 6 years of age, or between about 3 and about 5 years of age.

[0170] In preferred embodiments, the subject is an infant. In some embodiments, the subject is a newborn. In some embodiments, the subject is a preterm infant.

[0171] In some embodiments, the subject is about 5 years old or younger, about 4 years old or younger, about 3 years old or younger, about 2 years old or younger, or about 1 year old or younger. In some embodiments, the subject is about 12 months old or younger, about 11 months old or younger, about 10 months old or younger, about 9 months old or younger, about 8 months old or younger, about 7 months old or younger, or about 6 months old or younger. In some embodiments, the subject is about 9 months old or younger.

[0172] In some embodiments, the one or more HMOs are administered to the subject during the first, third, sixth, nineth, twelve, eighteen, fourteen, or thirty-sixth months of life. For example, the one or more HMOs are administered to the subject starting at birth and continuing through twelve, eighteen, twenty-four, or thirty-six months of age.

[0173] The subject may be at risk for poor behavioral development. Major risks for poor child development include intrauterine growth restriction, growth stunting, iodine deficiency, iron deficiency anemia, malaria, lead exposure, HIV, maternal depression, and lack of cognitive stimulation. Maternal education and breastfeeding have also been identified as protective factors (Walker, SP, et al., 2011. The Lancet, 378(9799), pp.1325-1338). In some embodiments, the subject has and / or suffered from intrauterine growth restriction, growth stunting, iodine deficiency, iron deficiency anemia, malaria, lead exposure, HIV, perinatal depression, maternal depression, and / or lack of cognitive stimulation. The subject may be at risk for poor social-emotional skills. The subject may be at risk for negative emotions.

[0174] The subject may have had and / or may have inadequate behavioral development. Any suitable screening tool may be used (see, e.g., Johnson, S. and Marlow, N., 2006. Early human development, 82(3), pp. 173-183). The subject may have had and / or may have inadequate social-emotional skills. The subject may have had and / or may have negative affect. This may be measured by any method known in the art, for example, using the Infant Temperament Questionnaire (IBQ), e.g., the IBQ-Revised (IBQ-R). See, e.g., Gartstein, MA and Rothbart, MK, 2003. Infant behavior and development, 26(1), pp. 64-86. [Example]

[0175] The present invention is further described with reference to the following examples, it being understood that the invention as claimed is in no way intended to be limited by these examples.

[0176] Example 1 - Association between behavioral outcomes and human milk oligosaccharide (HMO) concentrations in breast milk We investigated the association of behavioral outcomes with concentrations of specific human milk oligosaccharides (HMOs) in breast milk or with composite scores representing specific groups of HMOs in breastfed infants.

[0177] A total of 195 infants were studied. Breast milk HMO levels were tested in breast milk collected at 2 and 3 months. Infant behavior was assessed with the Infant Temperament Questionnaire-Revised (IBQ-R). A regression modeling approach was used, with covariates including maternal net income, maternal socioeconomic background / education, weight, gestational age, and infant sex (covariates were imputed and missing values ​​were replaced with the population mean). The negative affect domain was constructed from several scales from the IBQR (a maternal self-rated measure of infant temperament), including sadness, fear, negative emotional expression in response to restrictions, activity level, and reduced reactivity.

[0178] Certain fucosylated HMOs (LNDFHI, as well as 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI) are associated with reduced negative affect in 9-month-old infants (see Table 1 below, Figures 1, 2, 4A, and 4B).

[0179] [Table 2]

[0180] Example 2 - Association of gross motor skills and visual perception with human milk oligosaccharide (HMO) concentrations in breast milk We investigated the association between gross motor skills and visual reception and the concentrations of specific human milk oligosaccharides (HMOs) in breast milk.

[0181] A total of 105 infants, aged 2 weeks to 12 months, were assessed using the Mullen Scales of Early Learning (MSEL), and caregiver breast milk samples were collected for HMO analysis. Of the 105 infants, 60 attended a single visit, while the remaining subjects attended up to four visits, resulting in a total of 170 MSEL assessments and breast milk samples. Breast milk was collected at each visit using standard procedures. MSEL assessments were performed between 3 and 24 months of age. Associations between BM levels of the 3FLs were assessed using linear regression models. Due to the cohort design, we had to eliminate the potential confounding effect of age on all five subscales using smoothing spline regression before conducting association analyses with the MSEL (Hastie TJ et al., Generalized additive models, Boca Raton, Florida, USA. CRC Press; 1990). Significant positive associations with 3FL were observed for visual reception (p=0.041, ES=6.34) and gross motor skills (p=0.027, ES=7.67) (see Figure 3).

[0182] Embodiment Various preferred features and embodiments of the present invention will now be described with reference to the following numbered paragraphs.

[0183] 1. One or more human milk oligosaccharides (HMOs) for use in supporting behavioral development in a subject, the HMO comprising or consisting of: (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), and lacto-N-fucopentaose II (LNFPII).

[0184] 2. Use of one or more human milk oligosaccharides (HMOs) to support behavioral development in a subject, wherein the one or more HMOs comprise or consist of: (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), and lacto-N-fucopentaose II (LNFPII).

[0185] 3. A method for supporting behavioral development in a subject, comprising administering to the subject an effective amount of one or more human milk oligosaccharides (HMOs), wherein the one or more HMOs comprise or consist of: (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), and lacto-N-fucopentaose II (LNFPII).

[0186] 4. One or more HMOs for use according to paragraph 1, the use according to paragraph 2 or the method according to paragraph 3, wherein said one or more HMOs comprises or consists of LNDFHI.

[0187] 5. One or more HMOs for use according to paragraph 1 or 4, the use according to paragraph 2 or 4, or the method according to paragraph 3 or 4, wherein the one or more HMOs comprise or consist of 2'FL, 3FL, LDFT, and LNFPII.

[0188] 6. One or more HMOs for use according to any one of paragraphs 1 or 4-5, the use according to any one of paragraphs 2 or 4-5, or the method according to any one of paragraphs 3 or 4-5, wherein the one or more HMOs are administered by oral administration.

[0189] 7. One or more HMOs for the use according to any one of paragraphs 1 or 4 to 6, the use according to any one of paragraphs 2 or 4 to 6, or the method according to any one of paragraphs 3 or 4 to 6, wherein said one or more HMOs are administered separately, simultaneously or sequentially, preferably said one or more HMOs are administered simultaneously.

[0190] 8. The one or more HMOs for use according to any one of paragraphs 1 or 4 to 7, the use according to any one of paragraphs 2 or 4 to 7, or the method according to any one of paragraphs 3 or 4 to 7, wherein the one or more HMOs are administered to the subject in a total amount of from about 0.5 g / day to about 10 g / day.

[0191] 9. One or more HMOs for use according to any one of paragraphs 1 or 4 to 8, the use according to any one of paragraphs 2 or 4 to 8, or the method according to any one of paragraphs 3 or 4 to 8, wherein LNDFHI is administered to the subject in an amount of from about 0.1 g / day to about 5 g / day.

[0192] 10. One or more HMOs for the use of any one of paragraphs 1 or 4 to 9, the use of any one of paragraphs 2 or 4 to 9, or the method of any one of paragraphs 3 or 4 to 9, wherein (i) 2'FL is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, (ii) 3FL is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, (iii) LDFT is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, and / or (iv) LNFPII is administered to the subject in an amount of about 0.1 g / day to about 5 g / day.

[0193] 11. One or more HMOs for use according to any one of paragraphs 1 or 4 to 10, the use according to any one of paragraphs 2 or 4 to 10, or the method according to any one of paragraphs 3 or 4 to 10, wherein the one or more HMOs are in the form of a nutritional composition.

[0194] 12. One or more HMOs for use according to paragraph 11, the use according to paragraph 11 or the method according to paragraph 11, wherein the nutritional composition is an infant formula, a follow-on formula or a growing-up milk, preferably wherein the nutritional composition is an infant formula.

[0195] 13. The one or more HMOs for use according to paragraph 11 or 12, the use according to paragraph 11 or 12, or the method according to paragraph 11 or 12, wherein the nutritional composition comprises the one or more HMOs in a total amount of from about 0.5 g / L to about 10 g / L.

[0196] 14. The one or more HMOs for use according to any one of paragraphs 11 to 13, the use according to any one of paragraphs 11 to 13, or the method according to any one of paragraphs 11 to 13, wherein the nutritional composition comprises LNDFHI in an amount of from about 0.2 g / L to about 2.0 g / L.

[0197] 15. One or more HMOs for the use of any one of paragraphs 11 to 14, the use of any one of paragraphs 11 to 14, or the method of any one of paragraphs 11 to 14, wherein the nutritional composition comprises (i) 2'FL in an amount of about 0.5 g / L to about 3.0 g / L, (ii) 3FL in an amount of about 0.2 g / L to about 2.0 g / L, (iv) LDFT in an amount of about 0.05 g / L to about 0.5 g / L, and / or (v) LNFPII in an amount of about 0.05 g / L to about 0.5 g / L.

[0198] 16. One or more HMOs for the use according to any one of paragraphs 1 or 4 to 15, the use according to any one of paragraphs 2 or 4 to 15, or the method according to any one of paragraphs 3 or 4 to 15, wherein the subject is a human subject.

[0199] 17. One or more HMOs for use according to any one of paragraphs 1 or 4 to 16, the use according to any one of paragraphs 2 or 4 to 16, or the method according to any one of paragraphs 3 or 4 to 16, wherein the subject is an infant, toddler or young child.

[0200] 18. One or more HMOs for use according to any one of paragraphs 1 or 4 to 17, the use according to any one of paragraphs 2 or 4 to 17, or the method according to any one of paragraphs 3 or 4 to 17, wherein the subject is an infant.

[0201] 19. One or more HMOs for use according to any one of paragraphs 1 or 4 to 18, the use according to any one of paragraphs 2 or 4 to 18, or the method according to any one of paragraphs 3 or 4 to 18, wherein the subject is about 12 months of age or less, about 11 months of age or less, about 10 months of age or less, or about 9 months of age or less.

[0202] 20. One or more HMOs for use according to any one of paragraphs 1 or 4 to 19, the use according to any one of paragraphs 2 or 4 to 19, or the method according to any one of paragraphs 3 or 4 to 19, wherein the one or more HMOs improve the social and emotional skills of the subject.

[0203] 21. One or more HMOs for use according to any one of paragraphs 1 or 4 to 20, the use according to any one of paragraphs 2 or 4 to 20, or the method according to any one of paragraphs 3 or 4 to 20, wherein the one or more HMOs reduce negative emotions in the subject.

[0204] 22. One or more HMOs for use according to paragraph 21, the use according to paragraph 21 or the method according to paragraph 21, wherein the subject's negative affect is measured by the Infant Temperament Questionnaire (IBQ), preferably the IBQ-Revised (IBQ-R).

[0205] 23. Use of one or more HMOs for improving social and emotional skills in a subject, wherein the one or more HMOs comprise or consist of (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), and lacto-N-fucopentaose II (LNFPII).

[0206] 24. Use of one or more HMOs for reducing negative emotions in a subject, wherein the one or more HMOs comprise or consist of (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), and lacto-N-fucopentaose II (LNFPII).

[0207] 25. The use according to paragraph 23 or 24, wherein the one or more HMOs comprise or consist of LNDFHI.

[0208] 26. The use of any one of paragraphs 23 to 25, wherein the one or more HMOs comprise or consist of 2'FL, 3FL, LDFT, and LNFPII.

[0209] 27. The use according to any one of paragraphs 23 to 26, wherein the one or more HMOs are administered by oral administration.

[0210] 28. The use according to any one of paragraphs 23 to 27, wherein the one or more HMOs are administered separately, simultaneously or sequentially, preferably the one or more HMOs are administered simultaneously.

[0211] 29. The use of any one of paragraphs 23 to 28, wherein the one or more HMOs are administered to the subject in a total amount of about 0.5 g / day to about 10 g / day.

[0212] 30. The use of any one of paragraphs 23 to 29, wherein LNDFHI is administered to the subject in an amount of about 0.1 g / day to about 5 g / day.

[0213] 31. The use of any one of paragraphs 23 to 30, wherein (i) 2'FL is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, (ii) 3FL is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, (iii) LDFT is administered to the subject in an amount of about 0.1 g / day to about 5 g / day, and / or (iv) LNFPII is administered to the subject in an amount of about 0.1 g / day to about 5 g / day.

[0214] 32. The use according to any one of paragraphs 23 to 31, wherein the one or more HMOs are in the form of a nutritional composition.

[0215] 33. The use according to paragraph 32, wherein the nutritional composition is an infant formula, a follow-on formula, or a growing-up milk, preferably wherein the nutritional composition is an infant formula.

[0216] 34. The use according to paragraph 32 or 33, wherein the nutritional composition comprises the one or more HMOs in a total amount of from about 0.5 g / L to about 10 g / L.

[0217] 35. The use of any one of paragraphs 32 to 34, wherein the nutritional composition comprises LNDFHI in an amount of about 0.2 g / L to about 2.0 g / L.

[0218] 36. The use of any one of paragraphs 32 to 35, wherein the nutritional composition comprises (i) 2'FL in an amount of about 0.5 g / L to about 3.0 g / L, (ii) 3FL in an amount of about 0.2 g / L to about 2.0 g / L, (iii) LDFT in an amount of about 0.05 g / L to about 0.5 g / L, and / or (v) LNFPII in an amount of about 0.05 g / L to about 0.5 g / L.

[0219] 37. The use according to any one of paragraphs 23 to 36, wherein the subject is a human subject.

[0220] 38. The use of any one of paragraphs 23 to 37, wherein the subject is an infant, toddler, or young child.

[0221] 39. The use of any one of paragraphs 23 to 38, wherein the subject is an infant.

[0222] 40. The use of any one of paragraphs 23 to 39, wherein the subject is about 12 months of age or less, about 11 months of age or less, about 10 months of age or less, or about 9 months of age or less.

[0223] 41. One or more HMOs for use according to any one of paragraphs 1 or 4 to 19, the use according to any one of paragraphs 2 or 4 to 19, or the method according to any one of paragraphs 3 or 4 to 19, wherein the one or more HMOs improve gross motor skills and / or visual reception in the subject.

[0224] 42. One or more HMOs for use according to paragraph 41, the use according to paragraph 41 or the method according to paragraph 41, wherein said one or more HMOs comprise or consist of 3FL.

[0225] Although the present invention has been described by example, it should be understood that variations and modifications can be made without departing from the scope of the invention as defined in the claims. Furthermore, where known equivalents exist for specific features, such equivalents are incorporated as if specifically referred to herein.

Claims

1. 1. One or more human milk oligosaccharides (HMOs) for use in supporting behavioral development in a subject, comprising: (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP-I), One or more HMOs comprising or consisting of lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

2. 2. The one or more HMOs for use according to claim 1, wherein said one or more HMOs comprises or consists of LNDFHI.

3. 3. The one or more HMOs for use according to claim 1 or 2, wherein the one or more HMOs comprise or consist of 2'FL, 3FL, LDFT, LNFPII, LNFP-I, LNFP-III, LND-I, MFLNH-III, LNFP-V, LNnDFH, and LNFP-VI.

4. The one or more HMOs for use according to any one of claims 1 to 3, wherein said one or more HMOs are administered by oral administration.

5. 5. One or more HMOs for use according to any one of claims 1 to 4, wherein said one or more HMOs are administered separately, simultaneously or sequentially, preferably said one or more HMOs are administered simultaneously.

6. The one or more HMOs for use according to any one of claims 1 to 5, wherein said one or more HMOs are administered to said subject in a total amount of from about 0.5 g / day to about 10 g / day.

7. The one or more HMOs for use according to any one of claims 1 to 6, wherein said one or more HMOs are in the form of a nutritional composition.

8. 8. One or more HMOs for use according to claim 7, wherein said nutritional composition is an infant formula, a follow-on formula or a growing-up milk, preferably said nutritional composition is an infant formula.

9. 9. The one or more HMOs for use according to claim 7 or 8, wherein the nutritional composition comprises one or more HMOs in a total amount of from about 0.5 g / L to about 10 g / L.

10. The one or more HMOs for use according to any one of claims 1 to 9, wherein the subject is an infant, toddler or young child, preferably the subject is an infant.

11. 11. The one or more HMOs for use according to any one of claims 1 to 10, wherein the subject is about 12 months or less, about 11 months or less, about 10 months or less, or about 9 months or less in age.

12. 12. One or more HMOs for use according to any one of claims 1 to 11, wherein said one or more HMOs improve the social and emotional skills of said subject.

13. 13. One or more HMOs for use according to any one of claims 1 to 12, wherein said one or more HMOs reduce negative affect in said subject, preferably said negative affect in said subject as measured by the Infant Temperament Questionnaire-Revised (IBQ-R).

14. 1. Use of one or more HMOs for improving social and emotional skills, wherein the one or more HMOs are selected from the group consisting of (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP 1. Use of a lactofuctose-containing saccharide comprising or consisting of lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

15. 1. Use of one or more HMOs for reducing negative emotions, wherein the one or more HMOs are selected from the group consisting of: (a) lacto-N-difucohexaose I (LNDFHI); and / or (b) 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose II (LNFPII), lacto-N-fucopentaose I (LNFP-I). , lacto-N-fucopentaose III (LNFP-III), lacto-N-difucohexaose I (LND-I), monofucosyl-lacto-N-hexaose III (MFLNH-III), lacto-N-fucopentaose V (LNFP-V), lacto-N-neodifucohexaose (LNnDFH), and lacto-N-fucopentaose VI (LNFP-VI).

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