Use of nutritional composition in assisting in improving memory

Abstract

The use of a nutritional composition in the preparation of a food product for assisting in improving the memory ability of offspring by means of ingestion by a mother. The nutritional composition comprises the following essential components: an active folate substance and N-acetylneuraminic acid. A mass ratio of the active folate substance to the N-acetylneuraminic acid is (0.0005-0.007):(1-5). The mother comprises a pregnant mother and / or a lactating mother, and the offspring comprises fetal offspring and / or infant offspring, and optionally childhood offspring.

Description

Use of a nutritional composition to assist in improving memory capacity TECHNICAL FIELD

[0001] The present invention belongs to the field of food, in particular to the use of a nutritional composition to assist in improving memory capacity, more particularly to the use of a nutritional composition comprising active folate species and N-acetylneuraminic acid by maternal intake to assist in improving memory capacity in offspring for non-therapeutic purposes. BACKGROUND

[0002] Neurodevelopment is a complex process, influenced by the interaction between genetic factors, environmental factors and experience acquisition. The fetal and infant periods are critical periods for brain formation and development, laying the foundation for cognitive, motor, socio-emotional skills from childhood to adulthood. At the same time, the fetal and infant periods are also critical periods for the formation and maturation of brain structure and function, which are very sensitive to environmental factors and require adequate nutrition, and abnormal changes may lead to long-term irreversible consequences.

[0003] Studies have shown that nutritional status in early life can affect brain development and have long-term effects on cognitive function, learning and memory capacity, leading to lasting changes. Nutrients such as protein, long-chain unsaturated fatty acids, choline, folate, etc. are essential for brain development by participating in specific biochemical pathways related to neuron and glial cell development and function, regulating processes such as neuron migration and proliferation, axon and dendrite growth, synapse formation, myelination, neural cell apoptosis, etc. Abnormal nutritional status during pregnancy can lead to neurodevelopmental disorders in offspring after birth, affecting not only the basic structure of brain tissue in offspring, but also increasing the risk of later neurological disorders through epigenetic mechanisms. Reasonable nutrition during pregnancy plays an important role in the later cognitive performance of offspring.

[0004] Folic acid is a B-vitamin that the human body cannot synthesize itself and must be obtained through additional intake. As an important co-factor of one-carbon unit metabolism, folic acid mediates the de novo synthesis of purines and thymidines in the body and regenerates homocysteine (Hcy) into methionine, thereby supporting a wide range of methylation reactions in the body, including DNA, protein, neurotransmitters, etc. Folic acid deficiency can lead to deoxyribonucleic acid synthesis disorders, affecting cell division and proliferation. Low folic acid levels during pregnancy are associated with a variety of defects in offspring, such as neonatal respiratory distress syndrome (NRDS), congenital heart defects, growth retardation, low birth weight, etc.

[0005] Methylene tetrahydrofolate reductase (MTHFR) plays an important role in the process of folate utilization in vivo, and mutations in the gene determining the synthesis of the enzyme can lead to corresponding diseases. MTHFR C667T has three genotypes of CC, CT and TT, corresponding enzyme activities are 100%, 65%, 30%, and TT genotype can greatly reduce the absorption and utilization of supplemented synthetic folate. 6S-5-methyltetrahydrofolate, also known as active folate, is the most active form of folate after it enters the human body and is metabolized. It can be directly absorbed and utilized by the human body, is not affected by the genotype of tetrahydrofolate reductase in the body, and will not mask the adverse reaction symptoms caused by vitamin B deficiency. It is a better form of folate supplementation.

[0006] In order to avoid adverse pregnancy, the existing technology has developed a pregnant woman nutritional supplement containing folate substances, for example,

[0007] Reference document 1 (CN105106217B) discloses a pregnant woman nutritional supplement containing L-methyl folate or L-methyl folate salt, arginine and vitamin B12; wherein, L-methyl folate avoids the problem of folate unable to be absorbed and converted due to genetic defects, and avoids the adverse reactions caused by the accumulation of folate in the body when pregnant women cannot absorb and convert folate; arginine can promote blood circulation and effectively meet the needs of pregnant women for more semi-essential amino acids during pregnancy; avoid the occurrence of common diseases of pregnant women such as pregnancy-induced hypertension and eclampsia, and pregnancy depression; at the same time, L-methyl folate and arginine have good fusion.

[0008] N-acetylneuraminic acid, also known as sialic acid, is an acetylated derivative of acidic sugar neuraminic acid. Studies have shown that N-acetylneuraminic acid in breast milk has important significance for promoting the development of the nervous system of infants and enhancing immunity. N-acetylneuraminic acid is involved in cell recognition, regulates neurogenesis, cell proliferation and migration, synapse formation, cell adhesion and axon guidance, and plays a key role in brain information transmission, nerve impulse and synapse formation. Sialic acid has a high content in the brain, milk, blood and neural tissue mucin of mammals, and has the highest content in the brain, and is an important component of gangliosides in structure and function. Studies have shown that because the content and structure of sialic acid in cow's milk are quite different from those in human milk, the overall score of cognitive development of breastfed infants is higher than that of infant formula fed infants.

[0009] Currently, there have been studies on N-acetylneuraminic acid in relation to brain and neural development, for example,

[0010] Reference document 2 (CN110169454A) discloses a child formula milk powder for protecting eyes and helping brain intelligence development, which comprises docosahexaenoic acid, arachidonic acid, lutein, N-acetylneuraminic acid, phosphatidylserine, (3R, 3”R)-dihydroxy-beta-carotene, phospholipid, vitamin, folic acid, taurine, choline chloride, ferrous sulfate, zinc sulfate; wherein, N-acetylneuraminic acid can promote synapse formation and promote neural development, improve memory, and have antiviral and resistance improving effects.

[0011] Reference document 3 (CN102946728B) discloses a method and composition for improving fetal and child health and development by using nutritional supplementation with, for example, sialic acid, which is provided to a woman pre-, during and / or post-pregnancy in the form of N-acetylneuraminic acid, which provides developmental benefits to the nervous system and / or brain of the fetus or child of the woman. SUMMARY

[0012] PROBLEMS TO BE SOLVED BY THE INVENTION

[0013] At present, the research focus of pregnant women's nutritional supplements is mainly concentrated on how to avoid adverse pregnancy and abnormal fetal development, and such research has been unable to meet the extensive needs in the market development process for providing benefits to the early brain development of human beings while ensuring the health of mothers and infants through nutritional supplementation.

[0014] Although there are currently studies on nutritional substances that can promote brain development and other related aspects, most of the nutritional interventions in these studies start from the infant stage. However, research shows that even if a nutritional substance is considered to be directly given to infants to exert specific health benefits, it does not mean that it can exert the same effects in the development process of the offspring of the mother when it is ingested by the mother.

[0015] Although, for example, reference document 3 described above studies the developmental benefits to the nervous system and / or brain of the fetus or child of a woman after she is given sialic acid, it only studies this single substance, sialic acid, and does not study the effects on the brain and neural development of the fetus or child of a woman when she is given sialic acid and other possible nutritional substances.

[0016] Therefore, there is still room for development for a combination of nutritional substances that can be ingested by the mother, especially starting from the pregnancy period, to regulate the nutritional environment of the mother and promote the brain development of her offspring in relation to the aspects of brain development.

[0017] To this end, the present application aims to provide a non-therapeutic purpose use of a nutritional composition in assisting the improvement of memory ability of offspring, which can pre-position the nutritional intervention window, improve the maternal nutritional environment during pregnancy, and create better nutritional conditions for the brain development of offspring while avoiding adverse pregnancy and childbirth.

[0018] Solution for solving the problem

[0019] The present application provides a use of a nutritional composition in the preparation of a food for improving the memory ability of a fetus offspring and / or an infant offspring and optionally a child offspring via the intake of the mother during pregnancy and / or the mother during lactation.

[0020] Specifically, the present application provides the following technical solutions:

[0021] [1]. A use of a nutritional composition in the preparation of a food for improving the memory ability of offspring via the intake of a mother, wherein the nutritional composition comprises the following essential components: an active folic acid substance and N-acetylneuraminic acid; and in the nutritional composition, the mass ratio of the active folic acid substance to the N-acetylneuraminic acid is (0.0005-0.007):(1-5); the mother includes a mother during pregnancy and / or a mother during lactation, and the offspring includes a fetus offspring and / or an infant offspring and optionally a child offspring.

[0022] [2]. The use according to [1], wherein the active folic acid substance includes at least one of 6S-5-methyltetrahydrofolate, 6S-5-methyltetrahydrofolate calcium, 6S-5-methyltetrahydrofolate sodium and 6S-5-methyltetrahydrofolate glucosamine salt.

[0023] [3]. The use according to [1] or [2], wherein in the nutritional composition, the mass ratio of the active folic acid substance to the N-acetylneuraminic acid is (0.0005-0.007):1.

[0024] [4]. The use according to any one of [1]-[3], wherein the food, after being ingested by the mother, assists in improving the memory ability of the offspring by maintaining the nervous system health of the offspring and / or improving the intestinal flora of the offspring.

[0025] [5]. The use according to [4], wherein the maintenance of the nervous system health of the offspring includes any one or more of reducing the damage of nerve cells in the brain tissue of the offspring, reducing the proliferation of microglia cells in the brain tissue of the offspring, and reducing the inflammatory response in the brain tissue of the offspring.

[0026] [6]. The use according to [5], wherein the reducing inflammation in the brain tissue of the offspring comprises reducing the content of IL-6 in the brain tissue of the offspring.

[0027] [7]. The use according to any one of [4] to [6], wherein the improving gut microbiota of the offspring comprises any one or more of increasing the relative abundance of Akkermansia in the gut of the offspring, increasing the relative abundance of Lactobacillus HT002 in the gut of the offspring, and reducing the relative abundance of Escherichia-Shigella in the gut of the offspring.

[0028] [8]. The use according to any one of [1] to [7], wherein the food product is a confectionery, a beverage, a dairy product, a bakery product, a dietary supplement, or a food for special dietary use.

[0029] [9]. The use according to any one of [1] to [8], wherein the food product is a food product for infants, a food product for children, a food product for adolescents, or a food product for adults; and the food product for adults is a food product for pregnant women, a food product for postpartum women, or a food product for pregnant and postpartum women.

[0030]

[0010] . The use according to any one of [1] to [9], wherein the food product comprises any one or more of the following ingredients: a plant product ingredient, an animal dairy product ingredient, an animal meat product ingredient, a functional additive ingredient, and any acceptable adjuvant.

[0031] Effects of the invention

[0032] By implementing the above technical solutions, the present invention has the following technical effects:

[0033] It has been found through a large number of studies that the combination of active folic acid substances and N-acetylneuraminic acid supplemented by pregnant and / or lactating mothers can help maintain the nervous system health of their offspring (for example, can reduce the damage of nerve cells in the brain tissue of the offspring, reduce the proliferation of microglia cells in the brain tissue of the offspring, and reduce the inflammatory response in the brain tissue of the offspring, etc.) and / or improve the gut microbiota of their offspring (for example, develop the gut microbiota of their offspring in a beneficial direction), thereby having a positive effect on the memory ability of their offspring. In particular, when the pregnant and / or lactating mothers supplement the active folic acid substances and N-acetylneuraminic acid in a certain ratio, the above effects are more significant. BRIEF DESCRIPTION OF DRAWINGS

[0034] Figure 1: IBA-1 immunohistochemical detection results in the brain tissue of offspring mice; wherein CK is a blank control group, AL is Example 1, AH is Example 2, BL is Example 3, BH is Example 4, AH+BL is Example 5, and AH+BH is Example 6.

[0035] Figure 2: Statistical results of Escherichia-Shigella changes in the feces of the offspring mice under the intervention of different substances; wherein, C is the control group, AL is Example 1, AH is Example 2, BL is Example 3, BH is Example 4, AHBL is Example 5, AHBH is Example 6, 1w, 2w, 3w respectively represent 1 week, 2 weeks, 3 weeks after the birth of the offspring mice.

[0036] Figure 3: Statistical results of Lactobacillus HT002 changes in the feces of the offspring mice under the intervention of different substances; wherein, C is the control group, AL is Example 1, AH is Example 2, BL is Example 3, BH is Example 4, AHBL is Example 5, AHBH is Example 6, 1w, 2w, 3w respectively represent 1 week, 2 weeks, 3 weeks after the birth of the offspring mice.

[0037] Figure 4: Statistical results of Akkermansia changes in the feces of the offspring mice under the intervention of different substances; wherein, C is the control group, AL is Example 1, AH is Example 2, BL is Example 3, BH is Example 4, AHBL is Example 5, AHBH is Example 6, 1w, 2w, 3w respectively represent 1 week, 2 weeks, 3 weeks after the birth of the offspring mice. DETAILED DESCRIPTION

[0038] 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.

[0039] I. Definition of Terms

[0040] In the present application, a numerical range indicated using "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.

[0041] In the present application, the meaning indicated using "may" includes both the meaning of performing a certain process and the meaning of not performing a certain process.

[0042] In the present application, "optional" or "optionally" means that the event or situation described next can occur or can not occur, and the description includes the case where the event occurs and the case where the event does not occur.

[0043] 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".

[0044] In the present application, the terms "comprising", "having", "including", or "containing" can mean "including" or "open-ended" and do not exclude additional, unrecited elements or method steps. At the same time, "comprising", "having", "including", or "containing" can also mean "closed" and exclude additional, unrecited elements or method steps.

[0045] In the present application, the term "about" is used to define the approximate values of the numerical ranges and parameters of the present application, which have been presented as precisely as possible. Unless explicitly stated otherwise, all ranges, quantities, numerical values and percentages used in the present application are to be understood as being modified by "about". Herein, "about" generally means within ±5%, ±3%, ±1%, or ±0.5% of a given value or range.

[0046] In the present application, "room temperature" means an indoor ambient temperature of 23 ± 2 °C.

[0047] In the present application, "animal milk" is used to designate a liquid obtained from the mammary glands of a mammal in the lactating period. The term "animal milk" is to be interpreted broadly and encompasses both raw milk (i.e. the liquid obtained directly from the mammary glands) and standardized dairy products.

[0048] In the present application, "gestation period" and "pregnancy" are used interchangeably to designate the period from fertilization to delivery.

[0049] In the present application, "lactation period" designates the period starting from the beginning of breastfeeding after delivery to the end of breastfeeding.

[0050] In the present application, "exclusively breastfed" means that the vast majority of the nutrients and / or energy ingested by the offspring originates from breast milk.

[0051] 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 originates from breast milk.

[0052] In the present application, "infants" designates the human population group under the age of 36 months.

[0053] In the present application, "infants" designates the human population group under the age of 12 months.

[0054] In the present application, "young children" designates the human population group between the age of 13 and 36 months.

[0055] In the present application, "children" designates the human population group having an age greater than 3 years and less than 12 years, in the growth and development period.

[0056] In the present application, "adolescents" designates the human population group having an age greater than or equal to 12 years and less than 18 years.

[0057] In the present application, "adult" means a human group with an age of 18 years or older.

[0058] 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.

[0059] II. Nutritional composition

[0060] The present application provides a nutritional composition comprising essential components: active folate and N-acetylneuraminic acid; and, in the nutritional composition, the mass ratio of the active folate to the N-acetylneuraminic acid is (0.0005-0.007):(1-5). The active folate in the present application refers to 6S-5-methyltetrahydrofolic acid and salts thereof.

[0061] The present application has found, through a large number of studies, that the combination of active folate and N-acetylneuraminic acid supplemented by the mother during the gestation period and / or the lactation period can help maintain the nervous system health of the offspring and / or improve the intestinal flora of the offspring, thereby assisting in improving the learning and memory ability of the offspring.

[0062] In some embodiments, the main effective components in the nutritional composition are active folate and N-acetylneuraminic acid, that is, the nutritional composition mainly relies on the active folate and N-acetylneuraminic acid contained therein to exert specific physiological activity functions, such as assisting in improving the memory ability of the offspring during the fetal period and / or the infant period and optionally the childhood of the offspring through the intake of the pregnant mother and / or the lactating mother.

[0063] In some embodiments, the "mother" and "offspring" in 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.

[0064] In some embodiments, the active folate in the present application includes at least one of 6S-5-methyltetrahydrofolic acid, 6S-5-methyltetrahydrofolic acid calcium, 6S-5-methyltetrahydrofolic acid sodium, and 6S-5-methyltetrahydrofolic acid glucosamine salt.

[0065] The present application does not make special limitations on the source of the above-mentioned active folate, and typically, it can be synthesized by the ordinary chemical synthesis method in the art, for example, using folic acid or the like as a raw material, through reduction, methylation, chiral resolution, and optional salification and the like steps.

[0066] In some specific embodiments, the active folate of the present application is any one of 6S-5-methyltetrahydrofolic acid, 6S-5-methyltetrahydrofolic acid calcium, 6S-5-methyltetrahydrofolic acid sodium and 6S-5-methyltetrahydrofolic acid glucosamine.

[0067] In some more specific embodiments, the active folate of the present application is 6S-5-methyltetrahydrofolic acid calcium, in view of the convenience of obtaining from raw materials and the universality of consumption.

[0068] The present application does not particularly limit the source of the specific N-acetylneuraminic acid, and typically, it can be extracted from natural resources containing sialic acid, such as bird's nest, egg, milk, etc.; or, it can be obtained by chemical and enzymatic synthesis, such as condensation of N-acetylglucosamine with potassium salt of di-tert-butyl oxalate, and decarboxylation under catalysis of alkali to generate N-acetylneuraminic acid, or production of N-acetylmannosamine with N-acetylneuraminic acid aldolase; or, it can be obtained by fermentation of suitable microorganisms such as Escherichia coli and Bacillus subtilis; or, it can be obtained by whole-cell synthesis.

[0069] In some embodiments, the nutritional composition of the present application consists of the active folate and the N-acetylneuraminic acid; and in the nutritional composition, the mass ratio of the active folate to the N-acetylneuraminic acid is (0.0005-0.007):(1-5).

[0070] In order to obtain a more optimal effect of improving the memory ability of the offspring via the intake of the pregnant mother and / or the lactating mother, in some preferred embodiments, the mass ratio of the active folate substance to N-acetylneuraminic acid in the nutritional composition provided by the present application is (0.0005-0.007): 1; for example, the mass ratio of the active folate substance to N-acetylneuraminic acid in the nutritional composition can be 0.0005: 1, 0.0007: 1, 0.0009: 1, 0.0011: 1, 0.0013: 1, 0.0015: 1, 0.0017: 1, 0.0019: 1, 0.0021: 1, 0.0023: 1, 0.0025: 1, 0.0027: 1, 0.0029: 1, 0.0031: 1, 0.0033: 1, 0.0035: 1, 0.0037: 1, 0.0039: 1, 0.0041: 1, 0.0043: 1, 0.0045: 1, 0.0047: 1, 0.0049: 1, 0.0051: 1, 0.0053: 1, 0.0055: 1, 0.0057: 1, 0.0059: 1, 0.0061: 1, 0.0063: 1, 0.0065: 1, 0.0067: 1, or 0.0069: 1, etc.; preferably, it can be (0.0005-0.006): 1; more preferably, it can be (0.0005-0.004): 1; even more preferably, it can be (0.0005-0.002): 1; further more preferably, it can be (0.001-0.002): 1.

[0071] The composition described in the present application is generally an artificially synthesized or compounded composition, i.e., a composition that is not natural, such as breast milk.

[0072] III. Use for assisting in improving the memory ability of the offspring

[0073] The present application proposes that after the active folate substance and N-acetylneuraminic acid are compounded, especially after being compounded in a specific ratio, the intake of the pregnant mother and / or the lactating mother helps to maintain the nervous system health of the offspring and / or improve the intestinal flora of the offspring, thereby assisting in improving the memory ability of the offspring, and the active folate substance and N-acetylneuraminic acid have a synergistic effect between the two substances, and the above-mentioned effect is more optimal than the active folate substance or N-acetylneuraminic acid alone. At the same time, the present application believes that the effect of the nutritional composition for assisting in improving the memory ability of the offspring via the intake of the mother not only targets the fetus present in the mother and the infant consuming breast milk, but this effect can also continue to the childhood of the offspring and has a lasting impact on the offspring.

[0074] Further, the present application provides use of the above nutritional composition in the manufacture of a foodstuff for ingestion by a mother, including a pregnant mother and / or a lactating mother, to assist in improving memory capacity of an offspring, including a foetus and / or an infant and optionally a child.

[0075] In some embodiments, the present application provides use of the above nutritional composition in the manufacture of a foodstuff for ingestion by a pregnant mother to assist in improving memory capacity of an offspring, including a foetus and optionally a child.

[0076] In some embodiments, the present application provides use of the above nutritional composition in the manufacture of a foodstuff for ingestion by a pregnant mother to assist in improving memory capacity of an offspring, including an infant and optionally a child.

[0077] In some embodiments, the present application provides use of the above nutritional composition in the manufacture of a foodstuff for ingestion by a pregnant mother to assist in improving memory capacity of an offspring, including a foetus and an infant and optionally a child.

[0078] In some embodiments, the present application provides use of the above nutritional composition in the manufacture of a foodstuff for ingestion by a lactating mother to assist in improving memory capacity of an offspring, including an infant and optionally a child.

[0079] In some embodiments, the present application provides use of the above nutritional composition in the manufacture of a foodstuff for ingestion by a mother, including a pregnant mother and a lactating mother, to assist in improving memory capacity of an offspring, including a foetus and optionally a child.

[0080] In some embodiments, the present application provides use of the above nutritional composition in the manufacture of a foodstuff for ingestion by a mother, including a pregnant mother and a lactating mother, to assist in improving memory capacity of an offspring, including an infant and optionally a child.

[0081] In some embodiments, the present application provides use of the above nutritional composition in the manufacture of a foodstuff for ingestion by a mother, including a pregnant mother and a lactating mother, to assist in improving memory capacity of an offspring, including a foetus and an infant and optionally a child.

[0082] Also, the present application for assisting in improving memory capacity of an offspring, including maintaining the nervous system health of an offspring and improving the gut microbiota of an offspring, is not for the purpose of treating or preventing a disease.

[0083] In some embodiments, the infant offspring described herein can or can not be breastfed, preferably are breastfed. In some embodiments, the breastfeeding described herein can be exclusive breastfeeding, predominant breastfeeding, or mixed breastfeeding with small amounts of other foods. In some alternative embodiments, the offspring described herein include fetal offspring and / or breastfed offspring and optionally child offspring.

[0084] In some embodiments, the foodstuff aids in improving the offspring's memory capacity by maintaining the offspring's nervous system health and / or improving the offspring's gut microbiota upon maternal ingestion of the foodstuff. In some embodiments, the foodstuff aids in improving the offspring's memory capacity by simultaneously maintaining the offspring's nervous system health and improving the offspring's gut microbiota upon maternal ingestion of the foodstuff.

[0085] In some specific embodiments, the maintaining the offspring's nervous system health includes any one or more of reducing neural cell damage in the offspring's brain tissue, reducing microglial cell proliferation in the offspring's brain tissue, and reducing inflammatory response in the offspring's brain tissue. In some specific embodiments, the maintaining the offspring's nervous system health simultaneously includes reducing neural cell damage in the offspring's brain tissue, reducing microglial cell proliferation in the offspring's brain tissue, and reducing inflammatory response in the offspring's brain tissue.

[0086] In some specific embodiments, the reducing inflammatory response in the offspring's brain tissue includes reducing the amount of IL-6 in the offspring's brain tissue.

[0087] In some specific embodiments, the improving the offspring's gut microbiota includes any one or more of increasing the relative abundance of Akkermansia in the offspring's gut, increasing the relative abundance of Lactobacillus HT002 in the offspring's gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring's gut. In some specific embodiments, the improving the offspring's gut microbiota simultaneously includes increasing the relative abundance of Akkermansia in the offspring's gut, increasing the relative abundance of Lactobacillus HT002 in the offspring's gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring's gut.

[0088] It has been found that Akkermansia microorganisms can regulate the immune system and 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 neurological and mental diseases related to memory capacity (such as Alzheimer's disease), and have the potential to be a therapeutic target for various neurological and mental 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 (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.). In addition, it has been found that the relative abundance of Lactobacillus HT002 genus in the intestines of APP / PS1 double transgenic mice is less than that of wild-type mice (Hu F, Gao Q, Zheng C, Zhang W, Yang Z, Wang S, Zhang Y, Lu T. Encapsulated lactiplantibacillus plantarum improves Alzheimer's symptoms in APP / PS1 mice. J Nanobiotechnology. 2024 Sep 20; 22(1): 582. doi: 10.1186 / s12951-024-02862-1.)

[0089] The present application has found that the supplementation of the nutritional composition to the pregnant mother can increase the relative abundance of Akkermansia and Lactobacillus HT002 in the offspring's intestinal tract and reduce the relative abundance of Escherichia-Shigella in the offspring's intestinal tract. Therefore, the present application believes that the supplementation of the nutritional composition to the pregnant mother and / or the lactating mother can not only benefit the health of the offspring's intestinal flora, but also help to improve the offspring's memory ability through the gut-brain axis regulation.

[0090] The present application does not particularly limit the food containing or prepared by the nutritional composition.

[0091] In some embodiments, the food of the present application is in the form of liquid or solid at room temperature.

[0092] In some embodiments, the food of the present application is a confectionery, such as a hard candy, a gel candy, a crisp candy, a pressed candy, an aerated candy, etc. In some embodiments, the food of the present application is a beverage, such as a carbonated beverage, a tea beverage, a coffee beverage, a fruit and vegetable juice beverage, a lactic acid bacteria beverage, etc. In some embodiments, the food of the present application is a dairy product, such as milk powder, cheese, yogurt, liquid milk, etc. In some embodiments, the food of the present application is a baked food, such as bread, cake, and biscuit, etc. In some embodiments, the food of the present application is a dietary supplement, such as a hard capsule, a soft capsule, a tablet, an oral liquid, a pill, a granule, and a powder, etc. In some embodiments, the food of the present application is a special dietary food, such as an infant formula, an infant complementary food, a complementary nutritional supplement, and a special medical purpose formula, etc.

[0093] In some embodiments, the food of the present application is an infant food, a child food, an adolescent food, or an adult food.

[0094] 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, wherein the pregnant woman food is suitable for pregnant women, the postpartum woman food is suitable for postpartum women, especially lactating women; preferably, the food is a pregnant woman formula milk powder, a postpartum woman formula milk powder, or a pregnant and postpartum woman oral liquid.

[0095] In some embodiments, the food of the present application is a pregnant woman nutritional composition set or a postpartum woman nutritional composition set.

[0096] In some embodiments, the mass ratio of the active folic acid substance to N-acetylneuraminic acid in the food of the present application is (0.0005-0.007):(1-5).

[0097] The present application does not particularly limit the absolute content of the active folate substance and the N-acetylneuraminic acid in the food, and the requirements of the local food-related laws and regulations can be met.

[0098] Taking 6S-5-methyltetrahydrofolate calcium and N-acetylneuraminic acid as an example, in some embodiments, the addition of the nutritional composition makes the content of 6S-5-methyltetrahydrofolate calcium in the food be 0.0001% to 0.9%, preferably 0.0002% to 0.8%, more preferably 0.0004% to 0.75% by mass percentage; and the content of N-acetylneuraminic acid be 0.05% to 5%, preferably 0.08% to 3%, more preferably 0.1% to 1%.

[0099] When the mass content of the active folate substance and the N-acetylneuraminic acid in the food is within the above range, and is ingested by a mother (for example, a human (i.e., a pregnant woman) or an animal (i.e., a pregnant female)), the brain development of the offspring can be significantly, particularly synergistically, improved, and at the same time, (other) various nutrients required by the human or animal body (including the mother and the offspring) can also be balanced.

[0100] In addition to the above-described components in the nutritional composition, the food can also contain other ingredients, such as ingredients commonly contained in formulae, for example, ingredients commonly contained in formulae for pregnant and lying-in women, such as milk powder or beverages, candies, etc.

[0101] In addition, according to the type of food and the final needs of the target object, in some embodiments, the food 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.

[0102] For the plant product ingredient, examples 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, kohlrabi, Brussels sprouts, garlic, basil, Oregon grass, or extracts thereof; cereals such as rice (indica rice, japonica rice, waxy rice), wheat (wheat, barley, oat, rye), corn, sorghum, millet, foxtail millet, broomcorn millet, 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.

[0103] For the animal milk product ingredient, examples include fresh milk derived from cows, sheep, and the like, 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, and the like.

[0104] For the animal meat product ingredient, examples include meat product ingredients of pigs, cows, sheep, aquatic products, or birds.

[0105] For the functional additive ingredient, examples include vitamin supplements, mineral supplements, nucleotide supplements, dietary fibers, functional polyunsaturated fatty acid supplements, and the like.

[0106] 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, sweetening agents, food essences, food colorants, and the like.

[0107] Examples

[0108] The embodiments of the present application will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are for illustrative purposes only and should not be construed as limiting the scope of the present application. In the examples, unless otherwise specified, the procedures were carried out under conventional conditions or under conditions recommended by the manufacturer. Unless otherwise specified, the materials or instruments used were commercially available conventional products.

[0109] Experimental animals and grouping used in the experiments

[0110] Select 70 female rats of 8 weeks old and 70 male rats of 8 weeks old, which are purchased from Hangzhou Medical College, with the animal qualification certificate number 20240318Aazz0100000836 and the production license number SCXK(Zhejiang)2024-002. The feeding conditions are as follows: the animals are raised in a barrier environment, the indoor temperature is 25±1℃, the humidity is 45±5%, the animals are free to drink water, and they are raised in a 12h light-dark alternating environment every day. This experiment is reviewed by the animal ethics committee of Southeast University, with the ethics number 20240316003.

[0111] After 3 days of adaptive feeding, the female and male rats are caged together at a ratio of 1:1, and the female rats are given gavage intervention starting from the appearance of the vaginal plug. The gavage is continuously given to the female rats until the offspring rats are weaned. The experimental group is given the corresponding dose of sample water solution according to the animal grouping, and the control group is given the corresponding dose of normal saline. The gavage is performed once a day, and the gavage is continuously performed for 6 weeks. The maintenance feed is given to each dose group. The low and high doses of active folic acid substances are 5.3 and 10.1(μg / d / each), and the low and high doses of N-acetylneuraminic acid are 1.5 and 7.5(mg / d / each). The specific doses of each group are shown in Table 1. The brain development-related indicators of the offspring rats are detected during the gavage process.

[0112] Table 1 Gavage doses of experimental animals

[0113] Instruments, consumables and reagents used in the experiment

[0114] The consumables, reagents and experimental instruments used in the experiment are shown in Tables 2 and 3.

[0115] Table 2 Main experimental consumables and reagents

[0116] Table 3 Main experimental instruments

[0117] Experimental Example 1: Nutritional substances improve the learning and memory ability of offspring rats

[0118] The Morries water maze experiment is mainly used to test the learning and memory ability of experimental animals to space position and orientation (spatial orientation), which 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. The specific experimental method is as follows.

[0119] 1. Positioning navigation experiment

[0120] After weaning, the pups were placed in the pool for 2 min to familiarize them with the maze environment. The pups were trained 4 times per day at a fixed time each day. The platform was placed in the first quadrant at the beginning of training. The pups were placed in the pool facing the wall from any of the four starting points, and the time taken to find the platform (escape latency) and the swimming path were recorded. If the pups found the platform or failed to find it within 90 s, they were taken to the platform by the experimenter and rested on the platform for 15 s before the next experiment. The average of the 4 training latencies each day was used as the learning score of the pups on that day. The directional navigation experiment lasted for 4 days.

[0121] 2. Spatial exploration experiment

[0122] On the fifth day, the platform was removed at the same time period, and the pups were placed in the water at a fixed point in the fourth quadrant. The video recorded the time spent in the quadrant where the original platform was located and the number of times the pups passed through the original platform location within 60 s. If the animals spent more time in the quadrant where the original platform was located and passed through the original platform location more times, it indicated that they had better long-term memory of the platform location.

[0123] 3. Other requirements during the experiment

[0124] The water temperature and environmental conditions in the maze were kept stable, and the training was performed at a fixed time each day. The light and reference signs around the maze were clear and unchanged. At the end of each day's experiment, the water on the surface of the pups was wiped off, the bedding was changed to keep the feeding environment dry, and the pups were allowed to drink and eat freely in the barrier environment.

[0125] 4. Data analysis of the water maze experiment

[0126] The Super Maze software was used to process the video files of the pups in the water maze and record and analyze the swimming trajectories of the pups in the water maze.

[0127] 5. Experimental results

[0128] Table 4. Number of times the pups crossed the platform area

[0129] The more times the animals passed through the original platform location, the better their spatial memory of the platform location. The results in Table 4 showed that, compared with the control group, the number of times the pups in Examples 1, 2, 3, 4, 5, and 6 crossed the platform area increased to varying degrees; among them, the number of times the pups in Examples 5 and 6 crossed the platform area increased to varying degrees compared with Examples 2, 3, and 4.

[0130] Results show that: compared with the blank control group, the platform crossing times of the sub-mice in the different dose groups of active folic acid alone and the different dose groups of N-acetylneuraminic acid alone are increased and show a trend of increasing with the increase of the dose; it is unexpectedly found that the platform crossing times of the sub-mice after the composition of active folic acid and N-acetylneuraminic acid are higher than the effect of single gavage, and the effect of the composition of high dose of active folic acid and high dose of N-acetylneuraminic acid in promoting the spatial memory of sub-mice is better.

[0131] Table 5 Platform latency of sub-mice (s)

[0132] The shorter the platform latency of the animal, the better its long-term memory of the platform position is. The results in Table 5 show that the platform latency of the sub-mice in Examples 1, 2, 3, 4, 5, and 6 is shortened to different degrees compared with the control group; among them, the platform latency of the sub-mice in Examples 5 and 6 is shortened to different degrees compared with Examples 2, 3, and 4, and the platform latency of the sub-mice in Example 6 is shorter than that in Example 5.

[0133] Results show that: compared with the blank control group, the platform crossing times of the sub-mice in the different dose groups of active folic acid alone and the different dose groups of N-acetylneuraminic acid alone are increased and show a trend of increasing with the increase of the dose; it is unexpectedly found that the platform crossing times of the sub-mice after the composition of active folic acid and N-acetylneuraminic acid are higher than the effect of single gavage, and the effect of the composition of high dose of active folic acid and high dose of N-acetylneuraminic acid in promoting the spatial memory of sub-mice is better.

[0134] Table 6 Platform area residence time of sub-mice (s)

[0135] The longer the platform area residence time of the animal, the better its long-term memory of the platform position is. The results in Table 6 show that the platform area residence time of the sub-mice in Examples 1, 2, 3, 4, 5, and 6 is increased to different degrees compared with the control group; among them, the platform area residence time of the sub-mice in Example 6 is increased to different degrees compared with Examples 2 and 4.

[0136] Results show that: compared with the blank control group, the platform crossing times of the sub-mice in the different dose groups of active folic acid alone and the different dose groups of N-acetylneuraminic acid alone are increased and show a trend of increasing with the increase of the dose; it is unexpectedly found that the platform crossing times of the sub-mice after the composition of active folic acid and N-acetylneuraminic acid are higher than the effect of single gavage, and the effect of the composition of high dose of active folic acid and high dose of N-acetylneuraminic acid in promoting the spatial memory of sub-mice is better.

[0137] Experimental Example 2: Nutrients maintain the nervous system health of offspring mice

[0138] After the brain tissue was thawed, it was rinsed in a physiological saline solution at 4°C to remove blood, and then the residual physiological saline solution in the brain tissue was absorbed with filter paper. The brain tissue was accurately weighed, and PBS solution was added at a ratio of 1:10 (0.1 g of tissue was added to 0.9 mL of PBS solution). A homogenizer was used to prepare a 10% homogenate, and the homogenate was used to detect the content of neural development-related proteins and inflammatory factors in the brain tissue.

[0139] 1. Detection of neuron-specific enolase (NSE) in the brain tissue of offspring mice: The content of NSE in the brain tissue of offspring mice was detected by an automatic enzyme marker according to an NSE enzyme-linked immunosorbent assay (Elisa) method.

[0140] 2. Detection of ionized calcium binding adaptor molecule-1 (IBA-1) in the brain tissue of offspring mice: The content of IBA-1 in the brain tissue of offspring mice was detected by an automatic enzyme marker according to an IBA-1 enzyme-linked immunosorbent assay (Elisa) method.

[0141] 3. IBA-1 immunohistochemical detection in the brain tissue of offspring mice:

[0142] Table 7. Antibody information and repair conditions

[0143] a. Paraffin section deparaffinization to water: sequentially place the section in an environmentally friendly deparaffinization solution I for 10 min, an environmentally friendly deparaffinization solution II for 10 min, an environmentally friendly deparaffinization solution III for 10 min, anhydrous ethanol I for 5 min, anhydrous ethanol II for 5 min, anhydrous ethanol III for 5 min, and distilled water.

[0144] b. Antigen repair: the repair conditions are shown in Table 7 above. During the repair process, the buffer should be prevented from excessive evaporation, and the section should not be dried. After the repair is completed, the section is naturally cooled. Place the slide in PBS (pH 7.4) and shake for 3 times for 5 min each time on a decolorization shaker.

[0145] c. Circle serum blocking: after the section is slightly shaken dry, use a histological pen to draw a circle around the tissue, and drop BSA (10% donkey serum is used for blocking when the primary antibody is goat-derived, and 3% BSA is used for blocking when the primary antibody is derived from other sources), and block for 30 min.

[0146] d. Add primary antibody: drop the prepared primary antibody, and place the section flat in a wet box for overnight incubation at 4°C.

[0147] e. Add secondary antibody: place the slide in PBS (pH 7.4) and shake for 3 times for 5 min each time on a decolorization shaker. Add the corresponding secondary antibody, and incubate at room temperature for 50 min in the dark.

[0148] f. DAPI counterstaining of cell nuclei: Place the slide in PBS (pH 7.4) and wash three times on a destaining shaker for 5 min each time. Add DAPI staining solution and incubate at room temperature in the dark for 10 min.

[0149] g. Quenching tissue autofluorescence: Wash the slide three times in PBS (pH 7.4) on a decolorizing shaker for 5 min each time. Add autofluorescence quencher solution B for 5 min, then rinse with running water for 10 min. (If observation of tissue autofluorescence is required, this step can be omitted.)

[0150] h. Mounting: Mount the slide with anti-fluorescence quenching mounting medium.

[0151] i. Image acquisition: DAPI excitation wavelength 330-380nm, emission wavelength 420nm; 488 excitation wavelength 465-495nm, emission wavelength 515-555nm; CY3 excitation wavelength 510-560nm, emission wavelength 590nm; CY5 excitation wavelength 608-648nm, emission wavelength 672-712nm.

[0152] j. Adopt The software automatically identifies and locates the cell nuclei of DAPI blue fluorescent cells and expands the cytoplasmic range; it reverses the color of the monochrome channel fluorescence image (positive signal is black, background is white), reads the black positive signal, and calculates the number of positive cells and different parameters such as area, integrated optical density (IOD), and tissue area.

[0153] 4. Interleukin-6 (IL-6) detection in the brain tissue of offspring mice: The IL-6 content in the brain tissue of offspring mice was detected using an automated microplate reader with reference to the IL-6 enzyme-linked immunosorbent assay (ELISA) method.

[0154] 5. Experimental Results

[0155] Table 8. NSE detection results in mouse brain tissue (pg / mg·prot)

[0156] NSE is an enzyme specific to neurons and neuroendocrine cells, and is a sensitive indicator for evaluating the degree of nerve cell damage and predicting prognosis. The results in Table 8 show that, compared to the control group, the NSE values ​​of the brain tissues of the offspring mice in Examples 2, 3, 5, and 6 were all reduced to varying degrees; the NSE value of the brain tissue of the offspring mice in Example 6 was reduced to varying degrees compared to Examples 2 and 4, and the NSE value of the brain tissue of the offspring mice in Example 5 was reduced to varying degrees compared to Examples 2 and 3.

[0157] Results show that: compared with the blank control group, the NSE value of the brain tissue of the offspring mice in the active folic acid substance different dose group and the N-acetylneuraminic acid different dose group gavaged alone has no significant difference, but it is unexpectedly found that the NSE value of the brain tissue of the offspring mice after gavaging the combination of active folic acid substance and N-acetylneuraminic acid is lower than that of gavaging alone, indicating that the combination of N-acetylneuraminic acid and active folic acid substance can obtain a better effect of reducing nerve cell damage.

[0158] Table 9 IBA-1 detection results of the brain tissue of the offspring mice (pg / mg·prot)

[0159] IBA-1 is specifically expressed in central nervous system microglial cells, and reducing microglial cell proliferation can reduce related neuroinflammation and synaptic damage. It is shown from the results in Table 9 that the IBA-1 value of the brain tissue of the offspring mice of examples 2, 3, 4, 5 and 6 has different degrees of reduction compared with the control group; among them, the IBA-1 value of the brain tissue of the offspring mice of example 6 has different degrees of reduction compared with examples 2 and 4.

[0160] Results show that: compared with the blank control group, the IBA-1 value of the brain tissue of the offspring mice in the high dose group of active folic acid substance and the different dose group of N-acetylneuraminic acid gavaged alone has different degrees of reduction; but it is unexpectedly found that the IBA-1 value of the brain tissue of the offspring mice after gavaging the combination of high dose of active folic acid substance and high dose of N-acetylneuraminic acid is lower than that of gavaging alone, indicating that the combination of high dose of active folic acid substance and high dose of N-acetylneuraminic acid can obtain a better effect of reducing microglial cell proliferation.

[0161] The IBA-1 immunohistochemical detection results of the brain tissue of the offspring mice show that: compared with the control group, the number and area of IBA-1 labeled microglial cell staining of the brain tissue of the offspring mice in examples 2, 3 and 6 are all lower, among them, the number and area of IBA-1 labeled microglial cell staining of the brain tissue of the offspring mice after intervention of the composition of example 6 are lower than those of examples 2 and 3, indicating that gavaging the mother mice with a certain dose of active folic acid substance and N-acetylneuraminic acid can reduce the activation of microglial cells in the brain tissue of the offspring mice. Therefore, it is unexpectedly found that the number and area of IBA-1 labeled microglial cell staining of the brain tissue of the offspring mice after gavaging the combination of high dose of active folic acid substance and high dose of N-acetylneuraminic acid are lower than those of gavaging alone, indicating that the combination of high dose of active folic acid substance and high dose of N-acetylneuraminic acid can obtain a better effect of reducing microglial cell proliferation.

[0162] Table 10 IL-6 detection results of the brain tissue of the offspring mice (pg / mg·prot)

[0163] IL-6 is synthesized by neurons and glial cells, and has a dual role of neuroprotection and neurotoxicity during brain injury, protecting or promoting nerve repair at normal physiological concentration or low content, but causing neuronal damage at high expression. As shown by the results in Table 10, the IL-6 values of the brain tissues of the offspring mice of Examples 1, 2, 4, 5, and 6 were reduced to different degrees compared with the control group; among them, the IL-6 value of the brain tissue of the offspring mice of Example 6 was reduced to a certain extent compared with Examples 2 and 4.

[0164] The results show that, compared with the blank control group, the IL-6 values of the brain tissues of the offspring mice in the different dose groups of active folic acid substances and the high dose group of N-acetylneuraminic acid alone have different degrees of reduction; but it is unexpectedly found that the IL-6 value of the brain tissue of the offspring mice after gavage with the combination of high-dose active folic acid substances and high-dose N-acetylneuraminic acid is significantly lower than that of gavage alone, indicating that the combination of high-dose active folic acid substances and high-dose N-acetylneuraminic acid can obtain a better effect of reducing inflammation in brain tissue.

[0165] Experimental Example 3: Nutritional substances improve the intestinal flora of offspring mice

[0166] High-throughput sequencing of bacteria in the fecal samples of the mother mice and the offspring mice was performed using 16S rDNA:

[0167] 1) Microbiome total DNA extraction: The total microbiome total DNA in the feces was extracted using the cetyltrimethylammonium bromide method (CTAB method), and the quality of DNA extraction was detected by agarose gel electrophoresis, and the DNA was quantified by ultraviolet spectrophotometer.

[0168] 2) PCR amplification: The V3-V4 region of bacterial 16s rDNA was selected for gene amplification and sequencing, the primer sequence is shown in Table 11 below, the PCR reaction system is shown in Table 12 below, and the PCR reaction conditions are shown in Table 13 below.

[0169] Table 11 Primer sequence

[0170] Table 12 Reaction system

[0171] Table 13 Reaction conditions

[0172] 3) The PCR product was purified by AMPure XT beads (Beckman Coulter Genomice, MA, USA), and quantified by Qubit (Invitrogen, USA).

[0173] 4) The purified PCR products were evaluated using an Agilent 2100 Bioanalyzer (Agilent, USA) and library quantification kit of Illumina (Kapa Biosciences, Wobum, MA, USA), and the qualified library concentration was above 2nM. 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 6000SP Reagent Kit (500 cycles).

[0174] 5) The double-end data obtained by sequencing was first split according to the Barcode information, and the adapter and Barcode sequence were removed, then the sequence was spliced to obtain the optimized sequence. After removing the chimeric sequence, OUT cluster analysis was performed, and the OUT representative sequence was taxonomic analysis. Based on the OUT cluster analysis results, OUT was analyzed by various diversity index and sequence depth detection; based on the taxonomic information, the colony structure statistical analysis was performed at each taxonomic level.

[0175] The genus level of the mother mouse fecal intestinal flora was analyzed. The relative content of Akkermansia in the control group did not change significantly before and after intervention, but the relative content of Akkermansia decreased. After the intervention of active folic acid and N-acetylneuraminic acid, the intestinal flora of the mother mouse changed greatly, specifically, the relative content of Lactobacillus in most intervention groups showed a decreasing trend; the relative abundance of Akkermansia in most intervention groups increased, and the relative content was higher than that of the control group, among which the high and low dose groups of active folic acid and N-acetylneuraminic acid showed a significant increasing trend. 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 flora of Examples 1, 2, 3, 4 and 5 increased and was higher than that of the control group. The results showed that the intake of a certain dose of active folic acid and N-acetylneuraminic acid during pregnancy can promote the increase of the relative content of beneficial bacteria in the intestinal flora of the mother mouse.

[0176] The Escherichia-Shigella level in the intestinal tract of the offspring mice is shown in Figure 2. The Escherichia-Shigella content in the intestinal flora 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.

[0177] The Lactobacillus HT002 level in the intestinal tract of the offspring mice is shown in Figure 3. The relative abundance of Lactobacillus HT002 in the intestinal flora of the offspring mice in each group was different when the offspring mice were 7 days old. The relative abundance of Lactobacillus HT002 in each group except Example 1 was lower than that in the control group. After 3 weeks of continuous breastfeeding, the relative abundance of Lactobacillus HT002 in each group increased, and the relative abundance of Lactobacillus HT002 in the offspring mice in Examples 2, 3 and 6 was higher than that in the control group.

[0178] The Akkermansia level in the intestinal tract of the offspring mice is shown in Figure 4. The relative abundance of Akkermansia in the intestinal flora 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 Examples 1, 2, 3, 4, 5 and 6 increased to different degrees compared with the control group.

[0179] The above results show that the intake of active folic acid substances and N-acetylneuraminic acid by the mother mice from the gestation period promotes the content of beneficial flora in the intestinal tract of the offspring mice, and thus has an improvement benefit on the memory ability of the offspring mice through the gut-brain axis regulation.

Claims

1. Use of a nutritional composition in the manufacture of a foodstuff for improving memory capacity in an offspring via maternal ingestion, characterized in that, The nutritional composition comprises essential components: an active folate substance and N-acetylneuraminic acid; and, in the nutritional composition, the mass ratio of the active folate substance to the N-acetylneuraminic acid is (0.0005-0.007):(1-5); the mother includes a pregnant mother and / or a lactating mother, and the offspring includes a fetal offspring and / or an infantile offspring and optionally a childhood offspring.

2. Use according to claim 1, characterized in that, The active folate substance includes at least one of 6S-5-methyltetrahydrofolate, 6S-5-methyltetrahydrofolate calcium, 6S-5-methyltetrahydrofolate sodium, and 6S-5-methyltetrahydrofolate glucosamine.

3. Use according to claim 1 or 2, characterized in that, In the nutritional composition, the mass ratio of the active folate substance to the N-acetylneuraminic acid is (0.0005-0.007):

1.

4. Use according to any one of claims 1 to 3, characterized in that, The foodstuff, after being ingested by a mother, helps to improve the memory ability of an offspring by maintaining the nervous system health of the offspring and / or improving the intestinal flora of the offspring.

5. Use according to claim 4, characterized in that, The maintenance of the nervous system health of the offspring includes any one or more of reducing neural cell damage in brain tissue of the offspring, reducing microglia cell proliferation in brain tissue of the offspring, and reducing inflammatory response in brain tissue of the offspring.

6. Use according to claim 5, characterized in that, The reduction of the inflammatory response in brain tissue of the offspring includes reducing the content of IL-6 in brain tissue of the offspring.

7. Use according to any one of claims 4 to 6, characterized in that, The improvement of the intestinal flora of the offspring includes any one or more of increasing the relative abundance of Akkermansia in the intestine of the offspring, increasing the relative abundance of Lactobacillus HT002 in the intestine of the offspring, and reducing the relative abundance of Escherichia-Shigella in the intestine of the offspring.

8. Use according to any one of claims 1 to 7, characterized in that, The foodstuff is a confectionery, a beverage, a dairy product, a bakery product, a dietary supplement, or a food for special medical purposes.

9. Use according to any one of claims 1 to 8, characterized in that, The foodstuff is an infant food, a children food, an adolescent food, or an adult food; the adult food is a pregnant woman food, a lying-in woman food, or a pregnant and lying-in woman food.

10. Use according to any one of claims 1 to 9, characterized in that, The foodstuff contains any one or more of the following ingredients: a plant product ingredient, an animal dairy product ingredient, an animal meat product ingredient, a functional additive ingredient, and any acceptable excipient.

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