Use of nutritional composition for assisting in improving memory ability

By ingesting a combination of active folic acid and fucoidan during pregnancy and lactation, the problem of neglecting nutritional intervention during pregnancy in existing technologies has been solved, resulting in a significant improvement in offspring's memory and nervous system health.

WO2026067909A1PCT designated stage Publication Date: 2026-04-02HEILONGJIANG FEIHE DAIRY CO LTD

Patent Information

Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Filing Date
2025-12-08
Publication Date
2026-04-02

AI Technical Summary

Technical Problem

Existing research mainly focuses on nutritional interventions during infancy and early childhood, neglecting the importance of pregnancy for offspring brain development and lacking nutritional interventions specifically designed for pregnancy to improve offspring memory.

Method used

A nutritional composition containing active folic acid and fucoidan is provided, which, when ingested by the mother during pregnancy and/or lactation, promotes the development of the offspring's nervous system, regulates the gut microbiota, reduces inflammatory response, and helps improve the offspring's memory.

Benefits of technology

Through mother-to-child transmission, it significantly increases the content of brain-derived neurotrophic factor in offspring brain tissue, reduces inflammatory factors, regulates gut microbiota, improves offspring memory, and the effects extend into childhood.

✦ Generated by Eureka AI based on patent content.

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Abstract

The use of a nutritional composition in the preparation of a food product for assisting in improving the memory ability in offspring, wherein the nutritional composition contains the following essential components: an active folic acid substance and fucosyllactose; and in the nutritional composition, the mass ratio of the active folic acid substance to the fucosyllactose is (0.0001-0.0015):(0.5-10). The food product exerts the effect of assisting in improving the memory ability in offspring, wherein the food product is ingested by a mother, the mother is preganant and / or lactating, and the offspring comprises fetal offspring and / or infant offspring and optionally childhood offspring.
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Description

Use of a nutritional composition for assisting in improving memory capacity TECHNICAL FIELD

[0001] The present application belongs to the field of food, in particular to the use of a nutritional composition for assisting in improving memory capacity, more particularly to the application of a nutritional composition for assisting in improving memory capacity of offspring through maternal-fetal transmission. BACKGROUND

[0002] The development of human brain starts at 2-3 weeks of gestation, and the basic structure of the brain has been established and the main compartments of the central and peripheral nervous system have been established by the end of the embryonic period (8 weeks of gestation). During the first 1000 days of life, brain tissue grows rapidly, and the growth rate during this period is the highest in the entire life cycle. The brain development during the gestation period and infancy lays the foundation for cognitive, learning, memory, motor, and social-emotional skills during childhood and adulthood.

[0003] The nutritional environment in the early life can have a profound impact on brain development, and the nutrition during the gestation period plays a crucial role in the entire fetal development process. However, existing researches mainly focus on nutritional intervention from the infant stage, and there are few studies on nutritional intervention from the gestation period to improve various aspects of brain development of offspring.

[0004] Folic acid is a B-vitamin that the human body cannot synthesize itself and must be obtained through additional intake. Folic acid is reduced to tetrahydrofolic acid with physiological activity by folic acid reductase, which acts as a coenzyme of the one-carbon unit transferase system in the body, plays a role in transferring one-carbon units, and further participates in important physiological activities such as nucleic acid synthesis, amino acid metabolism, hemoglobin synthesis, and synthesis of important methyl compounds. Folic acid deficiency can cause obstacles in deoxyribonucleic acid synthesis and affect cell division and reproduction. Folic acid deficiency can also cause placental dysplasia in pregnant women, leading to spontaneous abortion, intrauterine growth retardation of the fetus, premature birth, and low birth weight of the newborn. During the utilization of folic acid in the body, methylenetetrahydrofolate reductase (MTHFR) plays an important role, and mutations in the gene that determines the synthesis of the enzyme can lead to corresponding diseases. MTHFR C667T has three genotypes of CC, CT, and TT, and the corresponding enzyme activities are 100%, 65%, and 30%, respectively. The TT genotype can greatly reduce the absorption and utilization rate of supplemented synthetic folic acid. 6S-5-methyltetrahydrofolate, also known as active folic acid, is the most active form of folic acid formed after folic acid enters the human body, and can be directly absorbed and utilized by the human body, and is not affected by the genotype of methylenetetrahydrofolate reductase in the body.

[0005] At present, there are studies on active folic acid substances in assisting to improve memory and other brain or neural development related aspects. For example, reference document 1 (CN109288005B) discloses a composition, the ingredients of which include folic acid compounds, algal oil DHA powder, nervonic acid and N-acetylneuraminic acid, wherein the folic acid compounds are one or more of folic acid, formyltetrahydrofolic acid, 6S-5-methyltetrahydrofolic acid, L-methylfolic acid, pharmaceutically acceptable salts of folic acid, active metabolites of folic acid or pharmaceutically acceptable salts of folic acid, and substances that can be metabolized and / or generate folic acid in vivo. Studies have found that the composition has the function of assisting to improve memory.

[0006] Human milk oligosaccharides (HMOs) are a group of oligosaccharides that infants cannot digest, and are the third largest nutrients in breast milk after lactose and lipids. Human milk oligosaccharides have the effects of promoting the growth of beneficial bacteria in the intestine, reducing the adhesion of intestinal pathogenic bacteria, promoting the maturation of the small intestine and surface glycosylation, etc. According to whether there is a sialic acid residue modification, human milk oligosaccharides can be divided into two categories: neutral human milk oligosaccharides and acidic human milk oligosaccharides. Among them, neutral human milk oligosaccharides can be further divided into fucosylated human milk oligosaccharides and non-fucosylated human milk oligosaccharides according to whether there is a fucose residue in the structure. The content of neutral human milk oligosaccharides in breast milk accounts for more than 70%, and the content of fucosylated human milk oligosaccharides in breast milk is 35% to 50%. The concentration of human milk oligosaccharides in breast milk shows dynamic changes during lactation, and fucosylated human milk oligosaccharides show different change patterns during lactation. 2'-fucosyllactose is the main fucosylated human milk oligosaccharide, and its concentration shows a gradual downward trend as the lactation period extends. The contents of other neutral human milk oligosaccharides (such as LNT, LNnT, LNFP I and LNFP V, etc.) show a downward trend as a whole although there is certain fluctuation in the whole lactation period. Similarly, the two main sialylated human milk oligosaccharides (6'-SL and 3'-SL) also show a downward trend as a whole during the lactation period.

[0007] Currently, there are studies on breast milk oligosaccharides in assisting to improve memory and other brain or neural development related aspects. For example, reference document 2 (CN112841317B) discloses a nutritional composition comprising 20%-35% of sialylated oligosaccharides and 50%-60% of fucosylated neutral oligosaccharides by weight percentage, wherein 2'-fucosyllactose accounts for 25%-35%. The nutritional composition has the effect of assisting to improve the intestinal microecology and learning and memory ability of infants fed by elderly mothers, and can be used for preparing infant formula milk powder or probiotic products. Reference document 3 (Li N, Xu K, Li L, et al. Research progress on physiological functions and preparation methods of 2'-fucosyllactose [J]. Food and Fermentation Industries, 2021, 47(23): 265-271.) discloses that 2'-FL has a certain effect on brain development, neuron transmission and synapse formation, and can stimulate brain development and improve memory. Reference document 4 (Falsaperla R, Sortino V, Gambilonghi F, Vitaliti G, Striano P. Human Milk Oligosaccharides and Their Pivotal Role in Gut-Brain Axis Modulation and Neurologic Development: A Narrative Review to Decipher the Multifaceted Interplay. Nutrients. 2024 Sep 5; 16(17): 3009.) discloses that HMOs can enhance long-term potentiation (LTP) by acting as prebiotics in the gut and undergoing bacterial fermentation to produce metabolites that penetrate the blood-brain barrier. In the cellular environment, these metabolites (such as short-chain fatty acids) are either used as cellular metabolic fuels or stimulate protein expression, thereby amplifying synaptic strengthening and LTP, such as brain-derived neurotrophic factor and calcium / calmodulin-dependent protein kinase II.

[0008] Currently, there are many studies on breast milk oligosaccharides in promoting the healthy development of infants and young children, but most of these studies start from the nutritional intervention of infants and young children, ignoring the important role of the environment during the entire pregnancy period on the future healthy development of infants and young children. There are few studies on nutritional supplementation during pregnancy to improve the brain development of offspring. SUMMARY

[0009] Problems to be solved by the invention

[0010] Currently, there are studies on nutrients that can assist in improving brain development-related aspects such as memory, but the nutritional intervention starting point of these studies is mostly in the infant stage. However, even if nutrients are considered to be directly given to infants to benefit development and health, it does not mean that they can promote the development and health of offspring via, for example, the maternal-fetal transmission pathway under the condition of maternal intake, and currently there are few studies on nutritional intervention starting from pregnancy.

[0011] Therefore, there is still room for development for nutrients and their combinations that can regulate the maternal nutritional environment via maternal intake, especially maternal intake starting from pregnancy, to promote brain development-related aspects of their offspring.

[0012] To this end, the purpose of the present application is to provide a use of a nutritional composition that can advance the nutritional intervention window, improve the nutritional environment during pregnancy, create better nutritional conditions for multiple aspects of brain development in offspring, assist in improving the memory ability of offspring, and further improve brain development in offspring while avoiding adverse pregnancy and childbirth.

[0013] Solution for solving the problem

[0014] The present application provides a use of a nutritional composition in the preparation of a foodstuff that, via intake by a mother who is in a pregnancy and / or lactation period, exerts a beneficial effect on brain development in an offspring who is in a fetal and / or infant period.

[0015] Specifically, the present application provides the following technical solutions:

[0016] [1]. A use of a nutritional composition in the preparation of a foodstuff that assists in improving the memory ability of an offspring, wherein,

[0017] The nutritional composition comprises the following essential components: an active folic acid substance and a fucosyllactose; and, in the nutritional composition, the mass ratio of the active folic acid substance to the fucosyllactose is (0.0001-0.0015):(0.5-10);

[0018] The foodstuff exerts the effect of assisting in improving the memory ability of the offspring via intake by a mother who is in a pregnancy and / or lactation period, the offspring including an offspring in a fetal and / or infant period and optionally an offspring in a childhood period.

[0019] [2]. The use according to [1], wherein,

[0020] The active folic acid substance includes at least one of 6S-5-methyltetrahydrofolate, 6S-5-methyltetrahydrofolate calcium, and 6S-5-methyltetrahydrofolate glucosamine salt.

[0021] [3]. The use according to [1] or [2], wherein,

[0022] The fucosyllactose comprises 2’-fucosyllactose.

[0023] [4]. The use according to any one of [1] to [3], wherein,

[0024] The foodstuff aids in improving memory capacity of an offspring via any one or more of promoting neural system development of the offspring, maintaining neural system health of the offspring, and modulating gut microbiota of the offspring after the foodstuff is ingested by a mother.

[0025] [5]. The use according to [4], wherein,

[0026] The promoting neural system development of the offspring comprises increasing the content of brain-derived neurotrophic factor in brain tissue of the offspring.

[0027] [6]. The use according to [4] or [5], wherein,

[0028] The maintaining neural system health of the offspring comprises reducing inflammatory response in brain tissue of the offspring.

[0029] [7]. The use according to [6], wherein,

[0030] The reducing inflammatory response in brain tissue of the offspring comprises reducing the content of IL-1β and / or TNF-α in brain tissue of the offspring.

[0031] [8]. The use according to any one of [4] to [7], wherein,

[0032] The modulating gut microbiota of the offspring comprises at least one of increasing relative abundance of Akkermansia in gut of the offspring, increasing relative abundance of Bacteroides in gut of the offspring, and reducing relative abundance of Escherichia-Shigella in gut of the offspring.

[0033] [9]. The use according to any one of [1] to [8], wherein,

[0034] The foodstuff is an infant foodstuff, a child foodstuff, an adolescent foodstuff, or an adult foodstuff; and the adult foodstuff is a pregnant woman foodstuff, a lying-in woman foodstuff, a pregnant and lying-in woman foodstuff, or an elderly foodstuff.

[0035]

[0010] . The use according to any one of [1] to [8], wherein,

[0036] The food contains any one or more of the following ingredients: a plant product ingredient, an animal milk product ingredient, an animal meat product ingredient, a functional additive ingredient, and any acceptable adjuvant.

[0037] Effects of the invention

[0038] Through the implementation of the above technical solutions, the present application has the following technical effects:

[0039] The present application has found through a large number of studies that the supplementation of active folic acid substances, fucosyllactose or a combination of active folic acid substances and fucosyllactose by the mother at the beginning of pregnancy can promote the development of the nervous system of the offspring, for example, increase the content of brain-derived neurotrophic factor in the brain tissue of the offspring, and can maintain the health of the nervous system of the offspring by reducing the inflammatory response in the brain tissue of the offspring, for example, reducing the content of inflammatory factors IL-1β and / or TNF-α in the brain tissue of the offspring, while also promoting the development of the intestinal flora of the offspring in a beneficial direction to improve the gut-brain axis regulation of the offspring, thereby assisting in improving the memory ability of the offspring. In particular, when the mother supplements active folic acid substances and fucosyllactose in a certain ratio at the beginning of pregnancy, the above effects are more optimal, thereby further significantly assisting in improving the memory ability of the offspring. BRIEF DESCRIPTION OF DRAWINGS

[0040] Figure 1: Statistical results of changes in Escherichia-Shigella in the feces of offspring mice under the intervention of different substances; wherein C is the control group, AL is Example 1, AH is Example 2, CL is Example 3, CH is Example 4, ALCL is Example 5, AHCL is Example 6, and AHCH is Example 7, 1w, 2w, and 3w represent 1 week, 2 weeks, and 3 weeks after the birth of the offspring mice, respectively.

[0041] Figure 2: Statistical results of changes in Akkermansia in the feces of offspring mice under the intervention of different substances; wherein C is the control group, AL is Example 1, AH is Example 2, CL is Example 3, CH is Example 4, ALCL is Example 5, AHCL is Example 6, and AHCH is Example 7, 1w, 2w, and 3w represent 1 week, 2 weeks, and 3 weeks after the birth of the offspring mice, respectively.

[0042] Figure 3: Statistical results of changes in Bacteroides in the feces of offspring mice under the intervention of different substances; wherein C is the control group, AL is Example 1, AH is Example 2, CL is Example 3, CH is Example 4, ALCL is Example 5, AHCL is Example 6, and AHCH is Example 7, 1w, 2w, and 3w represent 1 week, 2 weeks, and 3 weeks after the birth of the offspring mice, respectively. DETAILED DESCRIPTION

[0043] The following describes embodiments of the present application, but the present application is not limited thereto. Various modifications can be made within the scope of the present application, and embodiments obtained by appropriately combining the technical means disclosed in each of the different embodiments and examples are also included in the technical scope of the present application.

[0044] I. Definition of Terms

[0045] In the present application, a numerical range indicated by "numerical value A to numerical value B", "numerical value A - numerical value B", "numerical value A or more" or "numerical value A or less" means a range including the end point numerical values A and B.

[0046] In the present application, the meaning indicated by "may" includes both the meaning of performing a certain process and the meaning of not performing a certain process.

[0047] In the present application, "optional" or "optionally" means that the event or circumstance described next can or can not occur, and the description includes the case where the event occurs and the case where the event does not occur.

[0048] In the present application, the term "a" or "an" or "the" can mean "one", "one or more", "at least one" and "one or more than one".

[0049] In the present application, the term "comprise", "have", "include" or "contain" can mean inclusive or open-ended and does not exclude additional, unrecited elements or method steps. At the same time, "comprise", "have", "include" or "contain" can also mean closed- ended and exclude additional, unrecited elements or method steps.

[0050] In the present application, the term "about" is used to define the numerical ranges and parameters of the present application as approximate values, and the specific relevant values have been presented as accurately as possible. Unless otherwise explicitly stated, it should be understood that all ranges, numbers, values and percentages used in the present application are modified by "about". Here, "about" generally means that the actual value is within ±5%, ±3%, ±1% or ±0.5% of a certain value or range.

[0051] In the present application, "room temperature" means an indoor environmental temperature of 23±2°C.

[0052] In the present application, "animal milk" means a liquid obtained from mammary glands of a mammal in a lactating period. The term "animal milk" should be interpreted broadly and encompasses both raw milk (i.e., a liquid obtained directly from mammary glands) and standardized dairy products.

[0053] In the present application, "gestation period" and "pregnancy period" are used interchangeably and refer to the period from fertilization to delivery.

[0054] In the present application, "lactation period" refers to the period from the beginning of breastfeeding after delivery to the cessation of breastfeeding.

[0055] In the present application, "exclusively breastfed" means that the majority (at least 90%, preferably at least 95%, more preferably at least 98%) of the nutrients and / or energy ingested by the offspring is derived from breast milk.

[0056] In the present application, "predominantly breastfed" means that the majority (at least 50%, preferably at least 65%, more preferably at least 75%) of the nutrients and / or energy ingested by the offspring is derived from breast milk.

[0057] In the present application, "infants" refers to the group of human beings up to 36 months of age.

[0058] In the present application, "infants" refers to the group of human beings up to 12 months of age.

[0059] In the present application, "young children" refers to the group of human beings from 13 to 36 months of age.

[0060] In the present application, "children" refers to the group of human beings older than 3 years and younger than 12 years, in the growth and development phase.

[0061] In the present application, "adolescents" refers to the group of human beings older than or equal to 12 years and younger than 18 years.

[0062] In the present application, "adults" refers to the group of human beings older than or equal to 18 years.

[0063] In the present application, "elderly" refers to the group of human beings older than 45 years.

[0064] Unless otherwise defined, other technical and scientific terms used in the present application have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

[0065] II. Nutritional composition

[0066] The present application provides a nutritional composition comprising the essential components of: an active folate and a fucosyl lactose; and, in the nutritional composition, the mass ratio of the active folate to the fucosyl lactose is (0.0001-0.0015):(0.5-10). The active folate referred to in the present application is selected from 6S-5-methyltetrahydrofolate and salts thereof.

[0067] It is accidentally found in the research process that when the active folic acid substance and the fucosyllactose are used in a certain proportion, the two have a synergistic effect, and compared with the active folic acid substance or the fucosyllactose alone, the active folic acid substance and the fucosyllactose can obtain a better effect of assisting in improving the memory ability of offspring through, for example, a mother-infant transmission route by being ingested by a mother in a gestation period and / or a lactation period.

[0068] In some embodiments, the main effective component in the nutritional composition is the active folic acid substance and the fucosyllactose, that is, the nutritional composition mainly relies on the active folic acid substance and the fucosyllactose contained therein to exert a specific physiological activity function, for example, a function of assisting in improving the memory ability of offspring through, for example, a mother-infant transmission route by being ingested by a mother in a gestation period and / or a lactation period.

[0069] In some embodiments, the active folic acid substance in the present application includes at least one of 6S-5-methyltetrahydrofolic acid, 6S-5-methyltetrahydrofolic acid calcium, and 6S-5-methyltetrahydrofolic acid glucosamine salt.

[0070] The source of the active folic acid substance in the present application is not particularly limited, and typically, the active folic acid substance can be obtained by synthesizing through ordinary chemical synthesis methods in the art, for example, by using folic acid as a raw material, through steps of reduction, methylation, chiral resolution, and optional salification, and the like.

[0071] In some specific embodiments, the active folic acid substance in the present application is any one of 6S-5-methyltetrahydrofolic acid, 6S-5-methyltetrahydrofolic acid calcium, and 6S-5-methyltetrahydrofolic acid glucosamine salt.

[0072] In some more specific embodiments, considering the convenience of obtaining raw materials and the universality of consumption, the active folic acid substance in the present application is 6S-5-methyltetrahydrofolic acid calcium.

[0073] In some embodiments, the fucosyllactose in the present application includes 2'-fucosyllactose.

[0074] The source of the specific fucosyllactose in the present application is not particularly limited, and typically, the fucosyllactose can be obtained by synthesizing through ordinary chemical synthesis methods in the art, for example, by performing a glycosylation reaction of a lactose acceptor with a fucosyl donor, and the like; the fucosyllactose can also be obtained by microbial fermentation and the like, for example, by using exogenously added lactose as a substrate, using 5'-diphosphoguanosine fucose disodium salt formed by a metabolic pathway of microorganisms as a precursor, and synthesizing 2'-fucosyllactose under the action of a fucosyltransferase.

[0075] In some specific embodiments, the fucosyllactose in the present application is 2'-fucosyllactose.

[0076] In some specific embodiments, the nutritional composition according to the present application consists of the active folic acid substance and the fucosyllactose; and, in the nutritional composition, the mass ratio of the active folic acid substance to the fucosyllactose is (0.0001-0.0015):(0.5-10).

[0077] In order to obtain a more optimal effect of assisting in improving the memory ability of the offspring via the intake of the mother in the gestation period and / or lactation period, in some preferred embodiments, in the nutritional composition provided by the present application, the mass ratio of the active folic acid substance to the fucosyllactose is (0.0001-0.0015):1; for example, in the nutritional composition, the mass ratio of the active folic acid substance to the fucosyllactose can be 0.0001:1, 0.0002:1, 0.0003:1, 0.0004:1, 0.0005:1, 0.0006:1, 0.0007:1, 0.0008:1, 0.0009:1, 0.0010:1, 0.0011:1, 0.0012:1, 0.0013:1, 0.0014:1, 0.0015:1, etc.; preferably (0.0003-0.0010):1; more preferably (0.0004-0.0010):1; even more preferably (0.0006-0.0010):1.

[0078] The composition according to the present application is generally an artificially synthesized or compounded composition, i.e., not a natural composition such as breast milk.

[0079] III. Use of the nutritional composition

[0080] The present application proposes that, after the active folic acid substance and the fucosyllactose are compounded, especially in a specific ratio, the intake of the mother in the gestation period and / or lactation period can assist in improving the memory ability of the offspring, and the two substances have a synergistic effect, and the above-mentioned effect is more optimal than that of the active folic acid substance or the fucosyllactose alone. At the same time, the present application finds that the above-mentioned effect of assisting in improving the memory ability of the offspring is not only for the fetus existing in the mother and the infant consuming breast milk, but also for the infant who does not consume breast milk but is in sufficient contact with the mother, and at the same time, this regulatory effect can continue to the childhood of the offspring, and even has a lasting impact on the offspring.

[0081] Based on this, the present application provides the use of the above-mentioned nutritional composition in the preparation of a foodstuff for assisting in improving the memory ability of the offspring, and the foodstuff exerts the effect of assisting in improving the memory ability of the offspring via the intake of the mother, the mother is in the gestation period and / or lactation period, and the offspring includes the offspring in the fetal period and / or the infant period and optionally the offspring in the childhood.

[0082] In some embodiments, the present application provides the use of the above nutritional composition in the manufacture of a foodstuff for assisting in the improvement of memory capacity in an offspring, said foodstuff exerting said assisting in the improvement of memory capacity in an offspring via ingestion by a mother, said mother being in a gestation period, said offspring comprising a fetal period offspring and optionally a childhood offspring.

[0083] In some embodiments, the present application provides the use of the above nutritional composition in the manufacture of a foodstuff for assisting in the improvement of memory capacity in an offspring, said foodstuff exerting said assisting in the improvement of memory capacity in an offspring via ingestion by a mother, said mother being in a gestation period, said offspring comprising a fetal period offspring and optionally a childhood offspring.

[0084] In some embodiments, the present application provides the use of the above nutritional composition in the manufacture of a foodstuff for assisting in the improvement of memory capacity in an offspring, said foodstuff exerting said assisting in the improvement of memory capacity in an offspring via ingestion by a mother, said mother being in a gestation period, said offspring comprising a fetal period offspring and optionally a childhood offspring.

[0085] In some embodiments, the present application provides the use of the above nutritional composition in the manufacture of a foodstuff for assisting in the improvement of memory capacity in an offspring, said foodstuff exerting said assisting in the improvement of memory capacity in an offspring via ingestion by a mother, said mother being in a gestation period, said offspring comprising a fetal period offspring and optionally a childhood offspring.

[0086] In some embodiments, the present application provides the use of the above nutritional composition in the manufacture of a foodstuff for assisting in the improvement of memory capacity in an offspring, said foodstuff exerting said assisting in the improvement of memory capacity in an offspring via ingestion by a mother, said mother being in a gestation period, said offspring comprising a fetal period offspring and optionally a childhood offspring.

[0087] In some embodiments, the present application provides the use of the above nutritional composition in the manufacture of a foodstuff for assisting in the improvement of memory capacity in an offspring, said foodstuff exerting said assisting in the improvement of memory capacity in an offspring via ingestion by a mother, said mother being in a gestation period, said offspring comprising a fetal period offspring and optionally a childhood offspring.

[0088] In some embodiments, the present application provides the use of the above nutritional composition in the manufacture of a foodstuff for assisting in the improvement of memory capacity in an offspring, said foodstuff exerting said assisting in the improvement of memory capacity in an offspring via ingestion by a mother, said mother being in a gestation period, said offspring comprising a fetal period offspring and optionally a childhood offspring.

[0089] In some embodiments, the“mother” and“offspring” of the present application include mammals, including but not limited to humans, monkeys, chimpanzees, cows, sheep, cats, dogs, horses, rabbits, mice, rats, guinea pigs, and the like.

[0090] In some embodiments, the infant offspring of the present application can or can not be breastfed, preferably are breastfed. In some embodiments, the breastfeeding of the present application can be exclusive breastfeeding, predominant breastfeeding, or mixed breastfeeding with small amounts of breast milk and other foods.

[0091] The present application aids in improving the memory capacity of the offspring, including promoting the neural development of the offspring, maintaining the neural health of the offspring, and modulating the gut microbiota of the offspring, without the purpose of treating or preventing diseases.

[0092] In some embodiments, the food of the present application aids in improving the memory capacity of the offspring via any one or more of promoting the neural development of the offspring, maintaining the neural health of the offspring, and modulating the gut microbiota of the offspring, after the food is ingested by the mother.

[0093] In some specific embodiments, the promoting the neural development of the offspring includes increasing the level of brain-derived neurotrophic factor in the brain tissue of the offspring.

[0094] In some specific embodiments, the maintaining the neural health of the offspring includes reducing the inflammatory response in the brain tissue of the offspring. In some more specific embodiments, the reducing the inflammatory response in the brain tissue of the offspring includes reducing the level of IL-1β and / or TNF-α in the brain tissue of the offspring.

[0095] In some specific embodiments, the modulating the gut microbiota of the offspring includes at least one of increasing the relative abundance of Akkermansia in the gut of the offspring, increasing the relative abundance of Bacteroides in the gut of the offspring, and reducing the relative abundance of Escherichia-Shigella in the gut of the offspring.

[0096] It has been found that Akkermansia microorganisms can regulate the immune system, metabolic system through their metabolites such as short-chain fatty acids SCFAs, amino acids and amino acid derivatives, and thus play a comprehensive role in the gut-brain axis (Xu R, Zhang Y, Chen S, Zeng Y, Fu X, Chen T, Luo S, Zhang X. The role of the probiotic Akkermansia muciniphila in brain functions: insights underpinning therapeutic potential. Crit Rev Microbiol. 2023 Mar; 49(2): 151-176. doi: 10.1080 / 1040841X.2022.2044286.). Akkermansia microorganisms play an important role in various neuropsychiatric diseases (such as Alzheimer's disease, etc.), and have the potential to be a therapeutic target for various neuropsychiatric diseases. At the same time, it has been found that Escherichia-Shigella is increased in the fecal samples of Alzheimer's disease patients compared to healthy people's samples (Cryan JF, O'Riordan KJ, Sandhu K, Peterson V, Dinan TG. The gut microbiome in neurological disorders. Lancet Neurol. 2020 Feb; 19(2): 179-194. doi: 10.1016 / S1474-4422(19)30356-4. Epub 2019 Nov 18.). It has been found that the number of Bacteroides in the feces of children with autism decreases (Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, Soleimanpour S. A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders. Clin Microbiol Rev. 2022 Jan 19; 35(1): e0033820. doi: 10.1128 / CMR.00338-20.).

[0097] The present application has found that the supplementation of the nutritional composition to the mother during the pregnancy can increase the relative abundance of Akkermansia and Bacteroides in the gut of the offspring and decrease the relative abundance of Escherichia-Shigella in the gut of the offspring. Therefore, the present application believes that the supplementation of the nutritional composition or the food containing the nutritional composition to the mother during the pregnancy and / or lactation can not only benefit the gut microbiota of the offspring, but also benefit the brain development of the offspring through the gut-brain axis regulation, and thus improve the memory ability of the offspring.

[0098] The present application does not particularly limit the food containing the nutritional composition or prepared by the nutritional composition.

[0099] In some embodiments, the food of the present application is a confectionery, a beverage, a dairy product, a bakery product or a dietary supplement. Exemplarily, the confectionery includes hard candy, gummy candy, crisp candy, pressed candy and aerated candy, etc.; the beverage includes carbonated beverage, tea beverage, coffee beverage, fruit and vegetable juice beverage and lactic acid bacteria beverage, etc.; the dairy product includes fermented milk, cheese and milk powder, etc.; the bakery product includes bread, cake and biscuit, etc.; the dietary supplement includes hard capsule, soft capsule, tablet, oral liquid, granule and powder, etc.

[0100] In some embodiments, the food of the present application is a special dietary food; the special dietary food includes infant formula, infant complementary food, complementary nutritional supplement and special medical use formula, etc.

[0101] In some embodiments, the food of the present application is an infant food, a child food, an adolescent food or an adult food.

[0102] In some preferred embodiments, the food of the present application is a pregnant woman food, a postpartum woman food or a pregnant and postpartum woman food; the pregnant woman food is suitable for pregnant women to eat; the postpartum woman food is suitable for postpartum women, especially lactating women, to eat; preferably, the food is a pregnant woman formula milk powder, a postpartum woman formula milk powder or a pregnant and postpartum woman oral liquid.

[0103] In some embodiments, in the food of the present application, the mass ratio of the active folic acid substance to the fucosyl lactose is (0.0001-0.0015):(0.5-10), preferably (0.0001-0.0015):1.

[0104] The present application does not particularly limit the absolute content of the active folic acid substance and the fucosyl lactose in the food, which meets the requirements of the local food-related laws and regulations.

[0105] In some embodiments, the addition of the nutritional composition results in the food product having 6S-5-methyltetrahydrofolate in an amount of 0.0005% to 0.10%, preferably 0.0008% to 0.8%, more preferably 0.0010% to 0.75%, and 2'-fucosyllactose in an amount of 0.5% to 10%, preferably 1% to 8%, more preferably 2% to 6.5%, each by mass percentage, using 6S-5-methyltetrahydrofolate calcium and 2'-fucosyllactose as an example.

[0106] When the active folate and fucosyllactose in the food product are in the above ranges, and are ingested via the mother (e.g., a human (i.e., a pregnant woman) or an animal (i.e., a pregnant female)), the offspring's memory capacity can be significantly, particularly synergistically, improved, and at the same time, other aspects of nutrition required by the human or animal body (including the mother and the offspring) can also be balanced.

[0107] In addition to the above-described components in the nutritional composition, the food product can also contain other ingredients, such as ingredients often contained in formulae, such as formulae for pregnant and postpartum women, e.g., milk powder, such as proteins / amino acids, carbohydrates, fats, vitamins, minerals, etc.

[0108] In addition, according to the type of food product and the final needs of the target subject, in some embodiments, the food product also contains any one or more of the following ingredients: plant product ingredients, animal milk product ingredients, animal meat product ingredients, functional additive ingredients, and any acceptable adjuvants.

[0109] For plant product ingredients, examples can include fruits such as figs, pomegranates, kiwis, oranges, tangerines, pineapples, strawberries, apples, bananas, grapes, pears, cherries, blueberries, blackberries, blackcurrants, cranberries, raspberries, melons, emblics, and mulberries, or extracts thereof; fruit and vegetable materials such as onions, cucumbers, tomatoes, cauliflowers, red beetroots, spinach, kales, brussels sprouts, garlics, basil, oreganos, or extracts thereof; cereals such as rice (indica rice, japonica rice, waxy rice), wheat (wheat, barley, oat, rye), corn, sorghum, millet, foxtail millet, japonica, buckwheat, soybeans, fava beans, peas, mung beans, adzuki beans, kidney beans, or extracts thereof; nut materials such as walnuts, pistachios, cashews, hazelnuts, almonds, apricot kernels, pine nuts, peanuts, melon seeds, chestnuts, macadamia nuts, ginkgo nuts, or extracts thereof; coffee or extracts thereof; and some medicinal and edible plant materials or extracts thereof.

[0110] For the animal milk product ingredient, examples include raw milk derived from cows, sheep, etc., and reprocessed milk products such as whole milk powder, skim milk powder, concentrated whey protein powder, desalted whey powder, whey protein powder, hydrolyzed whey protein powder, casein powder, etc.

[0111] For the animal meat product ingredient, examples include meat product ingredients of pigs, cows, sheep, aquatic species, or birds.

[0112] For the functional additive ingredient, examples include vitamin supplements, mineral supplements, nucleotide supplements, dietary fibers, functional polyunsaturated fatty acid supplements, etc.

[0113] For any acceptable adjuvant, examples include solvents, antioxidants, antibacterial agents, thickening agents, diluents, co-solvents, stabilizers, emulsifiers, fillers, disintegrants, lubricants, coating materials, anti-caking agents, flavoring agents, sweeteners, food essences, food colorants, etc.

[0114] Examples

[0115] The embodiments of the present application will be described in detail below with reference to examples, but those skilled in the art will understand that the following examples are only for illustration of the present application and should not be considered as limiting the scope of the present application. In the examples, the specific conditions not noted are carried out according to the conventional conditions or the conditions recommended by the manufacturer. The materials or instruments used are commercially available conventional products unless otherwise specified.

[0116] Experimental animals and grouping used in the examples

[0117] Select 100 SPF female rats of 12 weeks of age and 100 SPF male rats of 12 weeks of age, weighing 350-410 g; purchased from Hangzhou Medical College, animal qualification certificate number 20240318Aazz0100000597, production license number: SCXK(Zhejiang)2024-002. Raising conditions: animals were raised in a barrier environment, indoor temperature 24±2℃, humidity 45±5%, animals were allowed to drink water freely, and were raised in a 12h light-dark alternating environment. This experiment was approved by the animal ethics committee of Southeast University, ethics number: 20240316003.

[0118] After 3 days of adaptive feeding, female and male rats were caged together in a 1:1 ratio, and the female rats were given intragastrical intervention starting from the appearance of a vaginal plug, and the female rats were continuously given intragastrical intervention until the offspring rats were weaned after 3 weeks. The experimental group was given the corresponding dose of sample aqueous solution according to the animal grouping, and the control group was given the corresponding dose of normal saline. Intragastrical administration was performed once a day, and the experiment lasted for 6 weeks. Each dose was given a maintenance feed. The low and high doses of active folic acid substances (6S-5-methyltetrahydrofolic acid calcium) were 5.3 and 10.1 (μg / d / each), and the low and high doses of 2'-fucosyllactose were 12.6 and 37.8 (mg / d / each). The specific doses of each group are shown in Table 1 below. After the end of intragastrical administration, the offspring rats were monitored for various indicators.

[0119] Table 1: Intragastrical administration dose of experimental animals

[0120] Instruments, consumables and reagents used in the examples

[0121] The main consumables, reagents and experimental instruments used in the experiment are shown in Tables 2 and 3.

[0122] Table 2: Main experimental consumables and reagents

[0123] Table 3: Main experimental instruments

[0124] Example 1: Nutritional substances improve the learning and memory ability of offspring rats

[0125] The Morries water maze experiment is mainly used to test the learning and memory ability of experimental animals to spatial position and orientation (spatial orientation), and is widely used in the fields of learning and memory, intelligence and aging research, and is widely recognized in the world. It is a classic experiment in behavioral science, especially in learning and memory research.

[0126] After the offspring rats were weaned and separated from the mother rats, the offspring rats were placed in a pool for free swimming for 2 min to familiarize them with the maze environment. Each time period was trained 4 times a day. At the beginning of the training, the platform was placed in the first quadrant, and the offspring rats were placed in the pool from any of the four starting points on the pool wall, facing the pool wall. The time for the offspring rats to find the platform (escape latency) and the swimming path were recorded. If the offspring rats found the platform or did not find the platform within 90 s, the experimenter would take them to the platform and rest for 15 s before the next experiment. The average value of the offspring rats' 4 training latencies per day was used as the learning score for the offspring rats on that day, and the positioning navigation experiment lasted for 4 days.

[0127] The platform was removed at the same time period on the 5th day, and the pups were fixed in the water in the fourth quadrant. The video recorded the residence time of the pups in the original platform quadrant within 60s and the number of times the pups passed through the original platform position. If the residence time of the animals in the original platform quadrant was longer and the number of times the animals passed through the original platform position was more, it indicated that the long-term memory of the animals for the platform position was better.

[0128] The stability of the water temperature and environmental conditions in the maze was maintained, the training was performed at a fixed time every day, the light around the maze and the reference signs were kept clear and unchanged, the surface water of the pups was wiped off at the end of the experiment every day, the bedding was replaced to keep the feeding environment dry, and the pups were fed freely in the barrier environment.

[0129] The Super Maze software was used to process the data of the video files of the pups in the water maze and record and analyze the swimming tracks of the pups in the water maze.

[0130] Table 4: Number of times the platform was crossed by the pups

[0131] The more times the animals passed through the original platform position, the better the long-term memory of the animals for the platform position was. The results in Table 4 showed that, compared with the control group, the number of times the platform was crossed by the pups in Examples 1, 2, 3, 4, 5, 6 and 7 increased to different extents, and the number of times the platform was crossed by the pups in Examples 3, 4, 5, 6 and 7 increased significantly. In addition, the number of times the platform was crossed by the pups in Examples 5, 6 and 7 was higher than that in Examples 1, 2 and 3.

[0132] The results showed that, compared with the blank control group, the number of times the platform was crossed by the pups in the different dose groups of the active folic acid substance and the different dose groups of 2'-fucosyllactose increased and showed a trend of increasing with the increase of the dose. It was unexpectedly found that the number of times the platform was crossed by the pups after the composition of the active folic acid substance and 2'-fucosyllactose was administered was higher than that after the active folic acid substance was administered alone, and the composition of the low-dose active folic acid substance and the low-dose 2'-fucosyllactose had a better effect on promoting the spatial memory of the pups.

[0133] Table 5: Platform residence time of the pups (s)

[0134] The longer the residence time of the animals in the platform quadrant, the better the long-term memory of the animals for the platform position was. The results in Table 5 showed that, compared with the control group, the residence time of the pups in the platform in Examples 1, 2, 3, 4, 5, 6 and 7 increased to different extents, and the residence time of the pups in the platform in Examples 1, 4, 5, 6 and 7 increased significantly. In addition, the residence time of the pups in the platform in Examples 5, 6 and 7 was higher than that in Examples 1, 2 and 3.

[0135] The results show that: compared with the blank control group, the platform stay time of the sub-mice in the active folic acid substance alone gavage different dose group and the 2'-fucosyllactose alone gavage different dose group is increased, among which the 2'-fucosyllactose alone gavage different dose group shows a trend of increasing effect with increasing dose; Unexpectedly, after gavage of the combination of low-dose and high-dose active folic acid substance and low-dose 2'-fucosyllactose, the platform stay time of the sub-mice is higher than that of the single gavage effect, and the combination of high-dose active folic acid substance and low-dose 2'-fucosyllactose has a better effect on promoting the spatial memory of sub-mice.

[0136] Experimental Example 2: Nutritional substances promote the development of the nervous system of sub-mice

[0137] After the brain tissue is thawed, it is rinsed in a 4°C pre-cooled physiological saline solution to remove blood, and then the residual physiological saline solution in the brain tissue is absorbed with filter paper. After accurate sampling and weighing, PBS solution is added at a ratio of 1:10 (0.1 g of tissue is added to 0.9 mL of PBS solution), and a 10% homogenate is prepared using a homogenizer. The homogenate is used to detect the content of nerve development proteins in the brain tissue.

[0138] The detection of brain-derived neurotrophic factor (BDNF) in the brain tissue of sub-mice is performed using a full-automatic enzyme marker, and the content of brain-derived neurotrophic factor in the brain tissue of sub-mice is detected according to the brain-derived neurotrophic factor enzyme-linked immunoassay (Elisa) method.

[0139] Table 6: Detection results of brain-derived neurotrophic factor in the brain tissue of sub-mice (ng / mg·prot)

[0140] Brain-derived neurotrophic factor is a protein molecule that has the functions of maintaining nerve cell survival, differentiation induction, promoting maturation, and regulating functions, and is expressed in nerve cells under physiological conditions and elevated by excitatory neurotransmission. According to the results in Table 6, the content of brain-derived neurotrophic factor in the brain tissue of sub-mice in Examples 1, 2, 3, 4, 5, 6, and 7 is increased to different degrees compared with the control group; in addition, the content of brain-derived neurotrophic factor in the brain tissue of sub-mice in Example 7 is higher than that in Examples 2 and 4, respectively.

[0141] The results show that: compared with the blank control group, the brain tissue brain-derived neurotrophic factor content of the offspring mice in the active folic acid substance alone gavage different dose group and the 2'-fucosyllactose alone gavage different dose group has different degrees of improvement, indicating that the single gavage has a certain degree of promoting effect on improving the content of brain tissue brain-derived neurotrophic factor; Unexpectedly, after gavage of the combination of active folic acid substance high dose and 2'-fucosyllactose high dose, the brain tissue brain-derived neurotrophic factor content of the offspring mice is higher than that of single gavage, indicating that the combination of 2'-fucosyllactose and active folic acid can obtain better effect of promoting the development of nervous system.

[0142] Experimental Example 3: Nutritional substances maintain the health of the nervous system of offspring mice

[0143] After the brain tissue is thawed, it is rinsed in a 4°C pre-cooled physiological saline solution to remove blood, and then the residual physiological saline solution in the brain tissue is absorbed with filter paper. After accurate sampling and weighing, PBS solution is added at a ratio of 1:10 (0.1 g of tissue is added to 0.9 mL of PBS solution), and a 10% homogenate is prepared using a homogenizer. The homogenate is used for inflammation factor detection.

[0144] (1) The brain tissue interleukin IL-1β (Interleukin-1β, IL-1β) detection of offspring mice is carried out using a full-automatic enzyme marker, and the IL-1β content of the brain tissue of offspring mice is detected according to the IL-1β enzyme-linked immunoassay Elisa method.

[0145] (2) The brain tissue tumor necrosis factor α (Tumor necrosis factor-α, TNF-α) detection of offspring mice is carried out using a full-automatic enzyme marker, and the TNF-α content of the brain tissue of offspring mice is detected according to the TNF-α enzyme-linked immunoassay Elisa method.

[0146] Table 7: Results of IL-1β detection in brain tissue of offspring mice (pg / mg·prot)

[0147] Studies have shown that IL-1 is produced by mononuclear, endothelial, fibroblastic or other cells in response to inflammatory reactions, plays an important role in immune response and tissue repair, and is involved in neuroprotection, tissue remodeling and repair. IL-1β is an effective pro-inflammatory cytokine, mainly secreted by lymphocytes, macrophages and monocytes. When there is viral infection or inflammation, the expression of pattern recognition receptors (PRRs) and Toll-like receptors (TLRs) increases, leading to increased expression of IL-1β. The results of IL-1β detection in the brain tissue of the sub-mice in Table 7 show that, compared with the control group, the IL-1β values in the brain tissue of the sub-mice in Examples 1, 2, 3, 4, 6, 7 are reduced to different degrees, among which the IL-1β values in the brain tissue of the sub-mice in Examples 1, 3, 4, 6 are significantly reduced; in addition, the degree of reduction of the IL-1β value in the brain tissue of the sub-mice in Example 6 is better than that in Examples 2 and 3.

[0148] The results show that, compared with the blank control group, the IL-1β values in the brain tissue of the sub-mice in the different dose groups of active folic acid alone and the different dose groups of 2'-fucosyllactose alone are reduced to different degrees, among which the different dose groups of 2'-fucosyllactose alone show a trend of increasing effect with increasing dose, indicating that the single administration of both has a certain degree of effect on reducing inflammatory factors; it is unexpectedly found that the IL-1β values in the brain tissue of the sub-mice after administration of the combination of high-dose active folic acid and low-dose 2'-fucosyllactose are all better than the single administration effect, indicating that the combination of 2'-fucosyllactose and active folic acid can achieve a better effect of reducing inflammatory response.

[0149] Table 8 TNF-α detection results in the brain tissue of sub-mice (pg / mg·prot)

[0150] TNF-α is produced by microglial cells and acts as an important cytokine, especially in the central nervous system, which is involved in the regulation of growth, development and various physiological activities of the nervous system. The results of TNF-α detection in the brain tissue of sub-mice are shown in Table 8. Compared with the control group, the TNF-α values in the brain tissue of sub-mice in Examples 1, 2, 3, 4, 6, 7 are reduced to different degrees, among which the TNF-α value in the brain tissue of sub-mice in Example 6 is significantly reduced; in addition, the TNF-α values in the brain tissue of sub-mice in Examples 6 and 7 are lower than those in Examples 2, 3 and 4.

[0151] Results showed that: compared with the blank control group, the TNF-a values of the offspring mice brain tissue in the active folic acid substance alone gavage different dose group and the 2'-fucosyllactose alone gavage different dose group were reduced to different degrees, among which the 2'-fucosyllactose gavage different dose group showed a trend of increasing effect with increasing dose, indicating that the single gavage had a certain degree of effect on reducing inflammatory factors; it was unexpectedly found that after gavage of the combination of high-dose active folic acid substance and low-dose 2'-fucosyllactose, the TNF-a values of the offspring mice brain tissue were reduced, and the reduction was better than that of the single gavage, indicating that the combination of 2'-fucosyllactose and active folic acid substance can obtain better effect of reducing inflammatory response.

[0152] Experimental Example 4: Nutritional substances regulate the intestinal flora of offspring mice

[0153] High-throughput sequencing of bacteria in the fecal samples of the mother mice and offspring mice was performed by 16S rDNA:

[0154] 1) Microbiome total DNA extraction: The total microbiome total DNA in the feces was extracted by the cetyltrimethylammonium bromide method (CTAB method), and the DNA extraction quality was detected by agarose gel electrophoresis, and the DNA was quantified by ultraviolet spectrophotometer.

[0155] 2) PCR amplification: The V3-V4 region of bacterial 16s rDNA was selected for gene amplification and sequencing, the primer sequence was shown in Table 9, the PCR reaction system was shown in Table 10, and the PCR reaction conditions were shown in Table 11.

[0156] Table 9 Primer sequence

[0157] Table 10 Reaction system

[0158] Table 11 Reaction conditions

[0159] 3) The PCR product was purified by AMPure XT beads (Beckman Coulter Genomice, MA, USA), and quantified by Qubit (Invitrogen, USA).

[0160] 4) The purified PCR product was evaluated using an Agilent 2100 Bioanalyzer (Agilent, USA) and a library quantification kit from Illumina (Kapa Biosciences, Wobum, MA, USA). The qualified library concentration was above 2 nM. The qualified sequencing library was gradient diluted, mixed according to the required sequencing amount, and denatured into single-stranded by NaOH for sequencing. The NovaSeq 6000 sequencer was used for 2x250bp double-end sequencing, and the corresponding reagent was NovaSeq 6000 SP Reagent Kit (500 cycles).

[0161] 5) The double-end data obtained by sequencing was first split according to the Barcode information, and the adapter and Barcode sequences were removed, and then the sequence was spliced to obtain the optimized sequence. After removing the chimeric sequence, OUT clustering analysis was performed, and OUT representative sequences were analyzed taxonomically. Based on the OUT clustering analysis results, OUT was analyzed by various diversity indices and sequence depth detection; based on the taxonomic information, statistical analysis of the colony structure was performed at each taxonomic level.

[0162] The mother mouse fecal intestinal flora genus level was analyzed. The relative content of Akkermansia and Lactobacillus in the control group did not change significantly before and after intervention, but the relative content of Akkermansia and Lactobacillus decreased. After the intervention of active folic acid substances and 2'-fucosyllactose, the intestinal flora of the mother mouse changed greatly, specifically, the relative content of Lactobacillus decreased in most intervention groups; in the active folic acid substance intervention group and the active folic acid substance high dose + 2'-fucosyllactose low dose group, the relative abundance of Akkermansia increased, and the relative content was higher than that of the control group; after delivery, the relative content of Lactobacillus in the active folic acid substance low dose group, 2'-fucosyllactose low dose group and active folic acid substance high dose + 2'-fucosyllactose high dose group increased, and the relative content was higher than that of the control group. At the end of the experiment, the relative abundance of Akkermansia in the control group was significantly reduced, and the relative abundance of Akkermansia in the mother mouse intestinal tract of Examples 1, 2, 3, 6 and 7 increased and was higher than that of the control group. The results showed that the intake of a certain dose of active folic acid substances and 2'-fucosyllactose during pregnancy can promote the increase of the relative content of beneficial bacteria in the mother mouse intestinal tract.

[0163] The Escherichia-Shigella content in the intestinal tract of the offspring mice is shown in Figure 1. The Escherichia-Shigella content in the intestinal tract of the mice in each group was high and was the dominant flora when the offspring mice were 7 days old. After 3 weeks of continuous breastfeeding, the relative abundance of Escherichia-Shigella in each group except Example 1 was lower than that in the control group.

[0164] The Akkermansia content in the intestinal tract of the offspring mice is shown in Figure 2. The relative abundance of Akkermansia in the intestinal tract of the offspring mice in each group was small when the offspring mice were 7 days old. After 3 weeks of continuous breastfeeding, the relative abundance of Akkermansia in the intestinal tract of the offspring mice in Example 1, 2, 3, 4, 5, and 6 was increased to different degrees compared with the control group.

[0165] The Bacteroides content in the intestinal tract of the offspring mice is shown in Figure 3. The relative abundance of Bacteroides in the intestinal tract of the offspring mice in each group was low and there was no significant difference between the groups when the offspring mice were 7 days old. After 3 weeks of continuous breastfeeding, the relative abundance of Bacteroides in the intestinal tract of the offspring mice in Example 2, 3, 6, and 7 was significantly increased compared with the control group.

[0166] In summary, the results show that the intake of active folate substances and 2'-fucosyllactose during pregnancy promotes the content of beneficial flora in the intestinal tract of the offspring mice, and the combination of high-dose active folate substances and low-dose 2'-fucosyllactose has better effects.

Claims

1. Use of a nutritional composition in the manufacture of a food for assisting in improving memory ability of an offspring, wherein the nutritional composition comprises essential components of an active folate substance and a fucosyl lactose; and, in the nutritional composition, the mass ratio of the active folate substance to the fucosyl lactose is (0.0001-0.0015):(0.5-10); and the food exerts the effect of assisting in improving memory ability of the offspring via ingestion by a mother who is in a gestation period and / or a lactation period, and the offspring includes a fetus period offspring and / or an infant period offspring and optionally a child period offspring.

2. The use according to claim 1, wherein the active folate substance includes at least one of 6S-5-methyltetrahydrofolate, 6S-5-methyltetrahydrofolate calcium and 6S-5-methyltetrahydrofolate glucosamine salt.

3. The use according to claim 1 or 2, wherein the fucosyl lactose includes 2'-fucosyllactose.

4. The use according to any one of claims 1-3, wherein the food assists in improving memory ability of the offspring via any one or more of promoting nervous system development of the offspring, maintaining nervous system health of the offspring and regulating intestinal flora of the offspring after ingestion by the mother.

5. The use according to claim 4, wherein the promoting nervous system development of the offspring includes increasing the content of brain-derived neurotrophic factor in brain tissue of the offspring.

6. The use according to claim 4 or 5, wherein the maintaining nervous system health of the offspring includes reducing inflammatory response in brain tissue of the offspring.

7. The use according to claim 6, wherein the reducing inflammatory response in brain tissue of the offspring includes reducing the content of IL-1β and / or TNF-α in brain tissue of the offspring.

8. The use according to any one of claims 4-7, wherein the regulating intestinal flora of the offspring includes at least one of increasing the relative abundance of Akkermansia in the intestinal tract of the offspring, increasing the relative abundance of Bacteroides in the intestinal tract of the offspring and reducing the relative abundance of Escherichia-Shigella in the intestinal tract of the offspring.

9. The use according to any one of claims 1-8, wherein the food is an infant food, a child food, an adolescent food or an adult food; and the adult food is a pregnant woman food, a lying-in woman food, a pregnant and lying-in woman food or an elderly food.

10. The use according to any one of claims 1-9, wherein the food contains any one or more of the following ingredients: a plant product ingredient, an animal milk product ingredient, an animal meat product ingredient, a functional additive ingredient and any acceptable adjuvant. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​

Citation Information

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