Application of nutritional composition for assisting in improving memory ability

Abstract

The invention belongs to the field of food, and particularly relates to application of a nutritional composition for assisting in improving memory ability. The invention provides application of a nutritional composition in preparation of food for assisting in improving memory ability of offspring. The nutritional composition comprises the following necessary components: active folic acid substances and fucosyllactose, moreover, 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 is ingested by a mother to play the role of assisting in improving the memory ability of the offspring, the mother is in a gestation period and / or a lactation period, and the maternal is in the gestation period and / or the lactation period. The filial generation comprises a fetal-stage filial generation and / or an infant-stage filial generation and an optional child-stage filial generation. A large number of studies find that when active folic acid substances and fucosyllactose which are combined according to a certain proportion are supplemented to a mother at the beginning of the gestation period, the memory ability of offspring can be remarkably improved in an auxiliary mode.

Description

Technical Field

[0001] The present invention belongs to the field of food, and specifically relates to the use of a nutritional composition for assisting in improving memory ability, and more specifically relates to the use of a nutritional composition for assisting in improving the memory ability of offspring through mother-to-infant transmission. Background Art

[0002] Human brain development begins at 2-3 weeks of gestation. By the end of the embryonic period (8 weeks of gestation), the basic structure of the brain has been established, and the main compartments of the central and peripheral nervous systems have also been established. In the first 1,000 days of life, brain tissue grows and develops rapidly, and the growth rate during this period is the highest in the entire life cycle. Brain development during pregnancy and infancy lays the foundation for cognitive, learning, memory, motor, and social-emotional skills in childhood and adulthood.

[0003] The nutritional environment in early life can profoundly affect brain development, and nutrition during pregnancy plays a vital role in the entire fetal development process. However, existing research mainly focuses on nutritional intervention from the infant stage, and there are few studies on nutritional intervention from pregnancy to improve the brain development of offspring.

[0004] Folic acid is a B vitamin that the human body cannot synthesize on its own and must be obtained through additional intake. Folic acid is reduced to physiologically active tetrahydrofolate by folate reductase, which plays a role as a coenzyme of the one-carbon unit transfer enzyme system in the body, plays the role of transferring one-carbon units, and further participates in important physiological activities such as nucleic acid synthesis, amino acid metabolism, hemoglobin and important methyl compound synthesis in the body. Folic acid deficiency can lead to disorders in the synthesis of deoxyribonucleic acid 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 newborns. In the process of folic acid being used in the body, methylenetetrahydrofolate reductase (MTHFR) plays an important role, and the gene mutation that determines the synthesis of this enzyme can lead to the occurrence of corresponding diseases. MTHFR C667T has three genotypes: CC, CT and TT, with corresponding enzyme activities of 100%, 65% and 30%. The TT genotype will 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 after it enters the human body. It can be directly absorbed and utilized by the human body and is not affected by the methylenetetrahydrofolate reductase genotype in the body.

[0005] At present, there have been studies on the role of active folic acid substances in assisting the improvement of memory and other aspects related to brain or nerve development. For example, reference 1 (CN109288005B) discloses a composition, the ingredients of which include folic acid compounds, algae oil DHA powder, neuraminic acid and N-acetylneuraminic acid, wherein the folic acid compound is one or more of folic acid, formyltetrahydrofolate, 6S-5-methyltetrahydrofolate, L-methylfolate, 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 the body. Studies have found that the composition has the function of assisting the improvement of memory.

[0006] Human milk oligosaccharides (HMOs) are a group of oligosaccharides that infants cannot digest. They are the third largest nutrient in breast milk after lactose and lipids. Human milk oligosaccharides have the functions of promoting the growth of beneficial intestinal bacteria, reducing the adhesion of intestinal pathogens, promoting small intestinal maturation and surface glycosylation. According to the presence or absence of 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 divided into fucosylated human milk oligosaccharides and non-fucosylated human milk oligosaccharides according to whether there are fucose residues 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%~50%. The concentration of human milk oligosaccharides in breast milk shows dynamic changes during lactation. 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 with the extension of lactation. Although the content of other neutral human milk oligosaccharides (such as LNT, LNnT, LNFP I and LNFP V, etc.) fluctuates to a certain extent throughout the lactation period, it shows an overall downward trend. Similarly, the two main sialylated human milk oligosaccharides (6'-SL and 3'-SL) also show an overall downward trend during the lactation period.

[0007] At present, there have been studies on the role of human milk oligosaccharides in assisting the improvement of memory and other aspects related to brain or neural development. For example, Reference 2 (CN112841317B) discloses a nutritional composition comprising 20%-35% by weight of sialylated oligosaccharides and 50%-60% of fucosylated neutral oligosaccharides, of which 2'-fucosyllactose accounts for 25%-35%. The nutritional composition has the function of assisting in improving the intestinal microecology and learning and memory ability of infants fed by older mothers, and can be used to prepare infant formula milk powder or probiotic products. Reference 3 (Li Na, Xu Kai, Li Li, et al. Research progress on the physiological effects and preparation methods of 2'-fucosyllactose [J]. Food and Fermentation Industries, 2021, 47(23): 265-271.) discloses that 2'-FL plays a certain role in brain development, neuronal transmission and synapse formation, and can stimulate brain development and improve memory. Reference 4 (Falsaperla R, Sortino V, Gambilonghi F, Vitaliti G, Striano P. Human Milk Oligosaccharides and Their Pivotal Role in Gut-BrainAxis Modulation and Neurologic Development: A Narrative Review to Decipherthe Multifaceted Interplay. Nutrients. 2024 Sep 5;16(17):3009.) discloses that HMO may enhance long-term potentiation (LTP) by acting as intestinal prebiotics 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 fuel or stimulate protein expression, thereby amplifying synaptic strengthening and LTP, such as brain-derived neurotrophic factor and phosphorylated calcium / calmodulin-dependent kinase II.

[0008] Currently, there are many studies on the role of human milk oligosaccharides in promoting the healthy development of infants and young children. However, the starting point of nutritional intervention in these studies is mostly from the infant stage, while ignoring the important role of the entire pregnancy environment in the future healthy development of infants and young children. There are very few studies on nutritional supplementation during pregnancy to improve the brain development of offspring. Summary of the invention

[0009] Problem that the invention aims to solve

[0010] Currently, there are studies on nutrients that can help improve memory and other aspects of brain development, but the starting point of nutritional intervention in these studies is mostly in the infant stage. However, even if nutrients are considered to be directly given to infants and young children to benefit their development and health, it does not mean that they can promote the development and health of offspring through, for example, mother-to-child transmission when ingested by the mother, and there are currently few studies on nutritional interventions starting during pregnancy.

[0011] Therefore, there is still room for development of nutrients and their combinations that can be ingested by the mother, especially from the beginning of pregnancy, to regulate the maternal nutritional environment and promote aspects related to brain development of her offspring.

[0012] In this regard, the purpose of the present invention is to provide a use of a nutritional composition, which can advance the nutritional intervention window, improve the nutritional environment during pregnancy, create better nutritional conditions for multiple related aspects of the brain development of the offspring, play a role in assisting in improving the memory ability of the offspring, and further improve the brain development of the offspring while avoiding adverse pregnancy and delivery.

[0013] Solutions for solving problems

[0014] The present invention provides a use of a nutritional composition in preparing a food that is ingested by a mother during pregnancy and / or lactation to contribute to the brain development of an offspring during a fetal period and / or an infant period.

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

[0016] [1]. Use of a nutritional composition in the preparation of a food for assisting in improving the memory ability of offspring, wherein:

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

[0018] The food plays the role of assisting in improving the memory ability of offspring when ingested by the mother, the mother being in the pregnancy and / or lactation period, and the offspring including the offspring in the fetal period and / or the offspring in the infant period and optionally the offspring in the 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 includes 2'-fucosyllactose.

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

[0024] After being ingested by the mother, the food helps improve the memory ability of the offspring by promoting any one or more of the development of the offspring's nervous system, maintaining the health of the offspring's nervous system, and regulating the offspring's intestinal flora.

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

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

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

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

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

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

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

[0032] The regulating the intestinal flora of the offspring includes at least one of increasing the relative abundance of Akkermansia in the offspring's intestine, increasing the relative abundance of Bacteroides in the offspring's intestine, and decreasing the relative abundance of Escherichia-Shigella in the offspring's intestine.

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

[0034] The food is infant food, children's food, adolescent food or adult food; the adult food is pregnant woman food, parturient woman food, pregnant and postpartum woman food or middle-aged and elderly people food.

[0035]

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

[0036] The food contains any one or more of the following ingredients: plant product ingredients, animal dairy product ingredients, animal meat product ingredients, functional added ingredients and any acceptable auxiliary materials.

[0037] Effects of the Invention

[0038] Through the implementation of the above technical solution, the present invention achieves the following technical effects:

[0039] The present invention has found through a large number of studies that the mother's supplementation of active folic acid substances, fucosylated lactose or a combination of active folic acid substances and fucosylated lactose at the beginning of pregnancy can promote the development of the offspring's nervous system through, for example, mother-to-child transmission, such as increasing the content of brain-derived neurotrophic factor in the offspring's brain tissue, and can reduce the inflammatory response in the offspring's brain tissue, such as reducing the content of inflammatory factors IL-1β and / or TNF-α in the offspring's brain tissue, thereby maintaining the health of the offspring's nervous system. At the same time, it can also promote the development of the offspring's intestinal flora in a beneficial direction, thereby improving the offspring's gut-brain axis regulation, and then have an auxiliary improvement effect on the memory ability of its offspring. In particular, when the mother supplements with active folic acid substances and fucosylated lactose in a certain ratio at the beginning of pregnancy, the above effect is better, so that the memory ability of the offspring can be further significantly assisted. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 : Statistical results of changes in Escherichia-Shigella in offspring mouse feces 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, AHCH is Example 7, 1w, 2w, 3w respectively represent 1 week, 2 weeks, and 3 weeks after the offspring mouse is born.

[0041] Figure 2 : Statistical results of changes in Akkermansia in offspring mouse feces 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, AHCH is Example 7, 1w, 2w, 3w respectively represent 1 week, 2 weeks, and 3 weeks after the offspring mouse is born.

[0042] Figure 3: Statistical results of changes in Bacteroides in offspring mouse feces 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, AHCH is Example 7, 1w, 2w, 3w respectively represent 1 week, 2 weeks, and 3 weeks after the offspring mouse was born. DETAILED DESCRIPTION

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

[0044] I. Definition of Terms

[0045] In the present invention, a numerical range expressed using “value A to value B”, “value A - value B”, “value A or more” or “value A or less” means a range including the endpoints A and B.

[0046] In the present invention, the word "may" includes both performing a certain process and not performing a certain process.

[0047] In the present invention, "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and the description includes instances where the event occurs and instances where it does not occur.

[0048] In the present invention, the term “a” or “an” or “the” may mean “one”, and may also mean “one or more”, “at least one” and “one or more than one”.

[0049] In the present invention, the terms "comprising", "having", "including" or "containing" may mean inclusive or open-ended, and do not exclude additional, uncited elements or method steps. At the same time, "comprising", "having", "including" or "containing" may also mean closed, excluding additional, uncited elements or method steps.

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

[0051] In the present invention, "normal temperature" refers to an indoor ambient temperature of 23±2°C.

[0052] In the present invention, "animal milk" is used to refer to the liquid obtained from the mammary gland of a mammal in the lactation period. The term "animal milk" should be interpreted broadly and covers both raw milk (ie, liquid obtained directly from the mammary gland) and standardized milk products.

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

[0054] In the present invention, the "breastfeeding period" refers to the period from the start of breastfeeding to the cessation of breastfeeding after a mother gives birth.

[0055] In the present invention, "exclusively breastfed" means that most (at least 90%, preferably at least 95%, more preferably at least 98%) of the nutrients and / or energy consumed by the offspring comes from breast milk.

[0056] In the present invention, the term "primarily fed with breast milk" means that the nutrients and / or energy intake of the offspring mainly (at least 50%, preferably at least 65%, more preferably at least 75%) comes from breast milk.

[0057] In the present invention, "infants" refers to a human group under 36 months of age.

[0058] In the present invention, "infant" refers to a human group under 12 months of age.

[0059] In the present invention, "infants" refers to a human group aged 13 to 36 months.

[0060] In the present invention, "children" refers to a human group that is older than 3 years old and younger than 12 years old and is in the growth and development stage.

[0061] In the present invention, "teenagers" refers to a human group aged 12 years or older and younger than 18 years old.

[0062] In the present invention, "adult" refers to a human group of people aged 18 years or older.

[0063] In the present invention, "middle-aged and elderly" refers to a human group over the age of 45.

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

[0065] II. Nutritional composition

[0066] The present invention provides a nutritional composition, which comprises the following essential components: active folic acid substances and fucosyllactose; and in the nutritional composition, the mass ratio of the active folic acid substances to the fucosyllactose is (0.0001-0.0015): (0.5-10). The active folic acid substances described in the present invention are selected from 6S-5-methyltetrahydrofolate and its salts.

[0067] The present invention unexpectedly discovered during the research process that when active folic acid substances and fucosyllactose are used in combination in a certain ratio, there is a synergistic effect between the two. Compared with active folic acid substances or fucosyllactose alone, it can obtain a better effect of assisting in improving the memory ability of offspring through, for example, mother-to-child transmission through ingestion by mothers during pregnancy and / or lactation.

[0068] In some embodiments, the main effective ingredients in the nutritional composition are active folic acid substances and fucosyllactose, that is, the nutritional composition mainly relies on the active folic acid substances and fucosyllactose contained therein to exert specific physiologically active functions, such as assisting in improving the memory ability of the offspring through, for example, mother-to-child transmission through ingestion by mothers during pregnancy and / or lactation.

[0069] In some embodiments, the active folate described in the present invention includes at least one of 6S-5-methyltetrahydrofolate, 6S-5-methyltetrahydrofolate calcium and 6S-5-methyltetrahydrofolate glucosamine salt.

[0070] The present invention does not particularly limit the source of the above-mentioned active folic acid substances. Typically, they can be synthesized by common chemical synthesis methods in the art, such as using folic acid as a raw material, through reduction, methylation, chiral resolution and optional salt formation steps.

[0071] In some specific embodiments, the active folic acid substance described in the present invention is any one of 6S-5-methyltetrahydrofolate, 6S-5-methyltetrahydrofolate calcium and 6S-5-methyltetrahydrofolate 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 described in the present invention is 6S-5-methyltetrahydrofolate calcium.

[0073] In some embodiments, the fucosyllactose described herein comprises 2'-fucosyllactose.

[0074] The present invention does not particularly limit the source of the specific fucosyllactose. Typically, it can be synthesized by common chemical synthesis methods in the art, such as by glycosylation reaction between a lactose acceptor and a fucosyl donor. It can also be obtained by microbial fermentation methods, such as using exogenously added lactose as a substrate and 5'-diphosphate guanosine-fucose disodium salt formed by the microorganism's own metabolic pathway as a precursor to synthesize 2'-fucosyllactose under the action of fucosyltransferase.

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

[0076] In some specific embodiments, the nutritional composition of the present invention 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 better effect of assisting in improving the memory ability of offspring through intake by mothers in pregnancy and / or lactation, in some preferred embodiments, in the nutritional composition provided by the present invention, the mass ratio of the active folic acid substance to the fucosyllactose is (0.0001-0.0015):1; illustratively, 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, 0.0016:1, 0.0017:1, 0.0018:1, 0.0019:1, 0.0020:1, 0.0021:1, 0.0022:1, 0.0023:1, 0.0024:1 .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 of the present invention is usually an artificially synthesized or compounded composition, that is, it is not a natural composition such as breast milk.

[0079] III. Uses of the nutritional composition

[0080] The present invention proposes that after active folic acid substances and fucosyllactose are compounded, especially after compounding in a specific ratio, they can be ingested by mothers in pregnancy and / or lactation to assist in improving the memory ability of their offspring, and there is a synergistic effect between the two substances, which is better than the active folic acid substances or fucosyllactose alone. At the same time, the present invention finds that the above-mentioned effect of assisting in improving the memory ability of offspring is not only for the fetus in the mother's body and infants who consume breast milk, but also for infants who do not consume breast milk but have full contact with their mothers. At the same time, this regulatory effect can also continue to the childhood of the offspring, and even have a lasting effect on the offspring.

[0081] Based on this, the present invention provides the use of the above-mentioned nutritional composition in the preparation of a food for assisting in improving the memory ability of offspring, wherein the food is ingested by the mother to exert the effect of assisting in improving the memory ability of the offspring, the mother is in pregnancy and / or lactation, and the offspring include fetal offspring and / or infant offspring and optionally childhood offspring.

[0082] In some embodiments, the present invention provides the use of the above-mentioned nutritional composition in the preparation of a food for assisting in improving the memory ability of offspring, wherein the food is ingested by a mother and exerts the effect of assisting in improving the memory ability of the offspring, wherein the mother is in pregnancy, and the offspring include fetal offspring and optionally childhood offspring.

[0083] In some embodiments, the present invention provides the use of the above-mentioned nutritional composition in the preparation of a food for assisting in improving the memory ability of offspring, wherein the food is ingested by a mother to exert the effect of assisting in improving the memory ability of the offspring, the mother is in pregnancy, and the offspring include infants and children and optionally children.

[0084] In some embodiments, the present invention provides the use of the above-mentioned nutritional composition in the preparation of a food for assisting in improving the memory ability of offspring, wherein the food is ingested by a mother to exert the effect of assisting in improving the memory ability of the offspring, wherein the mother is in pregnancy, and the offspring include fetal offspring, infant offspring, and optional childhood offspring.

[0085] In some embodiments, the present invention provides the use of the above-mentioned nutritional composition in the preparation of a food for assisting in improving the memory ability of offspring, wherein the food is ingested by a mother to exert the effect of assisting in improving the memory ability of the offspring, the mother is in a lactation period, and the offspring include infants and children and optionally children.

[0086] In some embodiments, the present invention provides the use of the above-mentioned nutritional composition in the preparation of a food for assisting in improving the memory ability of offspring, wherein the food is ingested by the mother to exert the effect of assisting in improving the memory ability of the offspring, the mother is in the pregnancy and lactation period, and the offspring include fetal offspring and optionally childhood offspring.

[0087] In some embodiments, the present invention provides the use of the above-mentioned nutritional composition in the preparation of a food for assisting in improving the memory ability of offspring, wherein the food is ingested by a mother to exert the effect of assisting in improving the memory ability of the offspring, wherein the mother is in a pregnancy and lactation period, and the offspring include infants and children and optionally children.

[0088] In some embodiments, the present invention provides the use of the above-mentioned nutritional composition in the preparation of a food for assisting in improving the memory ability of offspring, wherein the food is ingested by a mother to exert the effect of assisting in improving the memory ability of the offspring, wherein the mother is in a pregnancy or lactation period, and the offspring include fetal offspring, infant offspring, and optionally childhood offspring.

[0089] In some embodiments, the "mother" and "offspring" described in the present invention include mammals, including but not limited to humans, monkeys, gorillas, cows, sheep, cats, dogs, horses, rabbits, mice, rats or guinea pigs, etc.

[0090] In some embodiments, the infant offspring of the present invention may be fed with breast milk or not, preferably with breast milk. In some embodiments, the breastfeeding of the present invention may be completely fed with breast milk, may be mainly fed with breast milk, or may be mixed feeding with a small amount of breast milk and other foods.

[0091] The assistance in improving the memory ability of offspring (including promoting the development of the offspring's nervous system, maintaining the health of the offspring's nervous system and regulating the offspring's intestinal flora) described in the present invention is not intended to treat or prevent diseases.

[0092] In some embodiments, the food of the present invention, after being ingested by the mother, helps improve the memory ability of the offspring by promoting any one or more of the development of the offspring's nervous system, maintaining the health of the offspring's nervous system, and regulating the offspring's intestinal flora.

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

[0094] In some specific embodiments, the maintaining of the nervous system health of the offspring comprises 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 comprises reducing the content of IL-1β and / or TNF-α in the brain tissue of the offspring.

[0095] In some specific embodiments, said regulating the intestinal flora of the offspring comprises at least one of increasing the relative abundance of Akkermansia in the offspring's intestine, increasing the relative abundance of Bacteroides in the offspring's intestine, and decreasing the relative abundance of Escherichia-Shigella in the offspring's intestine.

[0096] Studies have shown that Akkermansia microorganisms can regulate the immune and metabolic systems 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 a variety of neuropsychiatric diseases (such as Alzheimer's disease) and have the potential to serve as therapeutic targets for various neuropsychiatric diseases. At the same time, studies have found that Escherichia-Shigella is increased in fecal samples of Alzheimer's patients compared with those in 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.). Studies have shown that the number of Bacteroides in the feces of children with autism is reduced (Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, Soleimanpour S. A Comprehensive Review on the Role of the Gut Microbiome in Human NeurologicalDisorders. Clin Microbiol Rev. 2022 Jan 19;35(1):e0033820. doi: 10.1128 / CMR.00338-20.).

[0097] The present invention has found that supplementing the above nutritional composition with the mother during pregnancy can increase the relative abundance of Akkermansia and Bacteroides in the intestines of her offspring and reduce the relative abundance of Escherichia-Shigella in the intestines of her offspring. Therefore, the present invention believes that by allowing the mother to supplement the above nutritional composition or food containing the above nutritional composition during pregnancy and / or lactation, it is not only beneficial to the health of the intestinal flora of her offspring, but also beneficial to the brain development of the offspring through the regulation of the gut-brain axis, and assists in improving the memory ability of the offspring.

[0098] The present invention does not particularly limit the specific food containing the above nutritional composition or the food that can be prepared with the above nutritional composition.

[0099] In some embodiments, the food of the present invention is candy, beverage, dairy product, baked food or dietary supplement. Exemplarily, the candy includes hard candy, jelly candy, crisp candy, tablet 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 baked food includes bread, cake and biscuits, etc.; the dietary supplement includes hard capsule, soft capsule, tablet, oral liquid, granule and powder, etc.

[0100] In some embodiments, the food described in the present invention is a special dietary food; the special dietary food includes infant formula, infant complementary food, complementary nutritional supplement and special medical purpose formula food, etc.

[0101] In some embodiments, the food of the present invention is infant food, children's food, adolescent food or adult food.

[0102] In some preferred embodiments, the food of the present invention is food for pregnant women, food for postpartum women or food for pregnant and postpartum women. The food for pregnant women is suitable for consumption by pregnant women, and the food for postpartum women is suitable for consumption by postpartum women, especially lactating women; preferably, the food is formula milk powder for pregnant women, formula milk powder for postpartum women or oral liquid for pregnant and postpartum women.

[0103] In some embodiments, in the food described in the present invention, the mass ratio of the active folic acid substance to the fucosyllactose is (0.0001~0.0015):(0.5~10), preferably (0.0001~0.0015):1.

[0104] The present invention does not particularly limit the specific absolute content of the active folic acid substance and the fucosyllactose in the food, as long as the requirements of local food-related laws and regulations are met.

[0105] Taking 6S-5-methyltetrahydrofolate calcium and 2'-fucosyllactose as examples, in some embodiments, the addition of the nutritional composition makes the content of 6S-5-methyltetrahydrofolate calcium in the food, by mass percentage, be 0.0005%~0.10%, preferably 0.0008%~0.8%, more preferably 0.0010%~0.75%; the content of 2'-fucosyllactose is 0.5%~10%, preferably 1%~8%, more preferably 2%~6.5%.

[0106] When the mass content of active folic acid substances and fucosyllactose in the food is within the above range and is consumed by the mother (e.g., a human (i.e., a pregnant woman) or an animal (i.e., a pregnant female)), it can significantly and especially synergistically assist in improving the memory ability of the offspring, and at the same time can also balance various (other) nutritional requirements of the human body or animal body (including the mother and the offspring).

[0107] In addition to the components described above for the nutritional composition, the food may also contain other ingredients, such as proteins / amino acids, carbohydrates, fats, vitamins, minerals, etc., which are often contained in formula foods, such as maternal formula foods such as milk powder.

[0108] In addition, depending on the type of food and the final needs of the applicable objects, in some embodiments, the food also contains any one or more of the following ingredients: plant product ingredients, animal dairy product ingredients, animal meat product ingredients, functional added ingredients and any acceptable excipients.

[0109] As for the ingredients of plant products, examples include fruits such as figs, pomegranates, kiwis, tangerines, oranges, pineapples, strawberries, apples, bananas, grapes, pears, cherries, blueberries, blackberries, black currants, cranberries, raspberries, melons, emblica chinensis and bilberry or their extracts; fruit and vegetable substances such as onions, cucumbers, tomatoes, cauliflower, carrots, spinach, kale, Brussels sprouts, garlic, basil, oregano or their extracts; grains such as rice (indica rice, japonica rice, glutinous rice), wheat (wheat, barley, oats, rye), corn, sorghum, millet, sorghum, yellow rice, buckwheat, soybeans, broad beans, peas, mung beans, red beans, kidney beans or their extracts; nuts such as walnuts, pistachios, cashews, hazelnuts, almonds, apricots, pine nuts, peanuts, melon seeds, chestnuts, macadamia nuts, ginkgo nuts or their extracts; coffee or its extracts; and some botanical Chinese medicinal materials or their extracts that are both medicinal and edible.

[0110] As for animal dairy ingredients, examples include fresh milk from cows, sheep, etc., as well as reprocessed dairy products such as whole milk powder, skim milk powder, concentrated whey protein powder, desalted whey powder, whey protein powder, hydrolyzed whey protein powder, and casein powder.

[0111] Examples of animal meat ingredients include meat ingredients from pigs, cattle, sheep, aquatic animals or poultry.

[0112] Functional added ingredients include vitamin supplements, mineral supplements, nucleotide supplements, dietary fiber, functional polyunsaturated fatty acid supplements, and the like.

[0113] As for any acceptable excipients, examples include solvents, antioxidants, antibacterial agents, thickeners, diluents, cosolvents, stabilizers, emulsifiers, fillers, disintegrants, lubricants, coating materials, anti-caking agents, flavoring agents, sweeteners, edible flavors, edible colorings, etc.

[0114] Example

[0115] The embodiments of the present invention will be described in detail below in conjunction with examples, but those skilled in the art will appreciate that the following examples are only used to illustrate the present invention and should not be considered to limit the scope of the present invention. If no specific conditions are specified in the examples, they are carried out under conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, the materials or instruments used are all conventional products that can be obtained commercially.

[0116] Experimental animals and groups used in the examples

[0117] 100 12-week-old sexually mature SPF female rats and 100 SPF male rats weighing 350-410 g were selected; purchased from Hangzhou Medical College, animal certificate number 20240318Aazz0100000597, production license number: SCXK (Zhejiang) 2024-002. Rearing conditions: Animals were raised in a barrier environment, with an indoor temperature of 24±2℃, humidity of 45±5%, free access to drinking water, and 12h light-dark alternation every day. This experiment passed the animal experiment ethics review of Southeast University, ethics number: 20240316003.

[0118] After 3 days of adaptive feeding, female and male rats were placed in the same cage at a ratio of 1:1. The intervention started when the mother rat showed vaginal plugs, and the mother rats were continuously gavaged until the offspring rats were weaned at 3 weeks old. The experimental group was divided into groups and given the corresponding dose of sample aqueous solution, and the control group was given the corresponding dose of normal saline, gavaged once a day for 6 weeks, and maintenance feed was given for each dose. The low and high doses of active folic acid substances (6S-5-methyltetrahydrofolate calcium) were 5.3 and 10.1 (μg / d / rat), and the low and high doses of 2'-fucosyllactose were 12.6 and 37.8 (mg / d / rat). The specific doses of each group are shown in Table 1 below. After the gavage, various indicators of the offspring were monitored.

[0119] Table 1 Oral dose of experimental animals

[0120]

[0121] Instruments, consumables and reagents used in the examples

[0122] The main consumables, reagents and experimental instruments used in the experiment are shown in Tables 2 and 3.

[0123] Table 2 Main experimental consumables and reagents

[0124]

[0125] Table 3 Main experimental instruments

[0126]

[0127] Experimental Example 1: Nutrients improve the learning and memory abilities of offspring mice

[0128] The Morries water maze experiment is mainly used to test the learning and memory ability of experimental animals regarding spatial position and orientation (spatial positioning). It is widely used in scientific research fields such as learning and memory, intelligence and aging. It is widely recognized in the world and is a classic experiment in behavioral science, especially in learning and memory research.

[0129] After the offspring were separated from the mother and weaned, they were placed in a pool and allowed to swim freely for 2 minutes to familiarize themselves with the maze environment. The training was conducted 4 times in a fixed time period every day. At the beginning of the training, the platform was placed in the first quadrant. The offspring was placed in the pool facing the pool wall from any of the four starting points on the pool wall. The time it took for the offspring to find the platform (escape latency) and the swimming path were recorded. After the offspring found the platform or failed to find the platform within 90 seconds, the experimenter took it to the platform and rested on the platform for 15 seconds before the next experiment. The average value of the offspring's 4 training latencies was used as the offspring's learning performance for the day. The positioning navigation experiment lasted for 4 days.

[0130] On the fifth day, the platform was removed at the same time, and the offspring was placed in the water at a fixed point in the fourth quadrant. The video recorded the time the offspring stayed in the quadrant where the original platform was located and the number of times it passed the original platform position within 60 seconds. If the animal stayed in the quadrant where the original platform was located for a longer time and passed the original platform position more times, it means that it has a good long-term memory of the platform position.

[0131] Keep the water temperature and environmental conditions in the maze stable, conduct training at a fixed time every day, keep the light and reference signs around the maze clear and unchanged, and at the end of each day's experiment, wipe off the moisture on the surface of the mice, replace the bedding to keep the breeding environment dry. At the same time, the mice are free to wade in water and eat, and are raised in a barrier environment.

[0132] Super Maze software was used to process the video files of the water maze test and to record and analyze the swimming trajectories of the water maze test mice.

[0133] Table 4 Number of times the rats crossed the platform area (times)

[0134]

[0135] The more times the animal passes through the original platform position, the better its long-term memory of the platform position. The results in Table 4 show that, compared with the control group, the number of platform crossings by the offspring mice in Examples 1, 2, 3, 4, 5, 6, and 7 increased to varying degrees, among which the number of platform crossings by the offspring mice in Examples 3, 4, 5, 6, and 7 increased significantly; in addition, the number of platform crossings by the offspring mice in Examples 5, 6, and 7 increased to varying degrees compared with Examples 1, 2, 3, and 4.

[0136] The results showed that compared with the blank control group, the number of platform crossings of offspring mice in the groups with different doses of active folic acid substances and different doses of 2'-fucosyllactose given intragastric administration increased, and showed an increasing trend with increasing doses; it was unexpectedly found that the number of platform crossings of offspring mice after intragastric administration of the combination of active folic acid substances and 2'-fucosyllactose was higher than that of the single intragastric administration, and the combination of the low-dose active folic acid group and the low-dose 2'-fucosyllactose group was more effective in promoting the spatial memory of offspring mice.

[0137] Table 5 The time that the rats stayed on the platform (s)

[0138]

[0139] The longer the animal stays in the quadrant where the platform is located, the better its long-term memory of the platform location is. The results in Table 5 show that, compared with the control group, the time that the offspring of Examples 1, 2, 3, 4, 5, 6, and 7 stay on the platform increases to varying degrees, among which the time that the offspring of Examples 1, 4, 5, 6, and 7 stay on the platform increases significantly; in addition, the time that the offspring of Examples 5, 6, and 7 stay on the platform is higher than that of Examples 1, 2, and 3.

[0140] The results showed that compared with the blank control group, the time that the offspring mice stayed on the platform in the groups with different doses of active folic acid substances and 2'-fucosyllactose was increased after oral gavage, among which the groups with different doses of 2'-fucosyllactose showed a trend of increasing effect with increasing dose. It was unexpectedly found that after oral gavage of the combination of low-dose and high-dose active folic acid substances plus low-dose 2'-fucosyllactose, the time that the offspring mice stayed on the platform was higher than that of the single gavage effect, and the combination of high-dose active folic acid substances and low-dose 2'-fucosyllactose was more effective in promoting the spatial memory of offspring mice.

[0141] Experimental Example 2: Nutrients Promote the Development of the Nervous System of Offspring Mice

[0142] After the brain tissue was thawed, it was rinsed in 4°C precooled saline solution to remove blood. After the residual saline solution in the brain tissue was absorbed with filter paper, a sample 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 10% homogenate was prepared using a homogenizer, and the homogenate was used to detect the content of neurodevelopmental protein in the brain tissue.

[0143] The brain-derived neurotrophic factor (BDNF) content in the brain tissue of the offspring mice was detected using a fully automatic microplate reader, and the brain-derived neurotrophic factor enzyme-linked immunosorbent Elisa method was used to detect the content of brain-derived neurotrophic factor in the brain tissue of the offspring mice.

[0144] Table 6 Detection results of brain-derived neurotrophic factor in offspring brain tissue (ng / mg·prot)

[0145]

[0146] Brain-derived neurotrophic factor is a protein molecule that has the functions of maintaining the survival of nerve cells, inducing differentiation, promoting maturation and regulating functions. It is expressed in nerve cells under physiological conditions and increases through excitatory neurotransmission. The results in Table 6 show that the content of brain-derived neurotrophic factor in the brain tissue of the offspring mice of Examples 1, 2, 3, 4, 5, 6, and 7 is increased to varying degrees compared with the control group; in addition, the content of brain-derived neurotrophic factor in the brain tissue of the offspring mice of Example 7 is higher than that of Examples 2 and 4, respectively.

[0147] The results showed that compared with the blank control group, the content of brain-derived neurotrophic factor in the brain tissue of offspring mice in the groups that were gavaged with different doses of active folic acid substances alone and different doses of 2'-fucosyllactose alone increased to varying degrees, indicating that gavage alone could promote the increase of brain-derived neurotrophic factor content in brain tissue to a certain extent; it was unexpectedly found that after gavage of the combination of high-dose active folic acid substances and high-dose 2'-fucosyllactose, the content of brain-derived neurotrophic factor in the brain tissue of offspring mice was higher than that of the single gavage effect, indicating that the combination of 2'-fucosyllactose and active folic acid substances can obtain a better effect in promoting the development of the nervous system.

[0148] Experimental Example 3: Nutrients maintain the health of the nervous system of offspring mice

[0149] After the brain tissue was thawed, it was rinsed in 4°C precooled saline solution to remove blood. After the residual saline solution in the brain tissue was absorbed with filter paper, a sample 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 10% homogenate was prepared using a homogenizer, and the homogenate was used for inflammatory factor detection.

[0150] (1) The interleukin-1β (IL-1β) content in the brain tissue of offspring mice was detected using a fully automatic microplate reader, and the IL-1β enzyme-linked immunosorbent assay (ELISA) method was used to detect the IL-1β content in the brain tissue of offspring mice.

[0151] (2) The detection of tumor necrosis factor-α (TNF-α) in the brain tissue of offspring mice was performed using a fully automatic microplate reader, and the TNF-α enzyme-linked immunosorbent assay (ELISA) method was used to detect the TNF-α content in the brain tissue of offspring mice.

[0152] Table 7 IL-1β detection results in brain tissue of offspring mice (pg / mg·prot)

[0153]

[0154] Studies have shown that IL-1 is produced by monocytes, endothelial cells, fibroblasts or other cells in response to inflammation, plays an important role in immune response and tissue repair, and participates in neuroprotection, tissue remodeling and repair. IL-1β is an effective proinflammatory cytokine, mainly secreted by lymphocytes, macrophages and monocytes. When there is a viral infection or inflammation, the increased expression of pattern recognition receptors (PRR) and Toll-like receptors (TLR) leads to enhanced expression of IL-1β. The results of IL-1β detection in the brain tissue of sub-mouse in Table 7 show that compared with the control group, the IL-1β values ​​of the brain tissue of sub-mouse in Examples 1, 2, 3, 4, 6, and 7 were reduced to varying degrees, among which the IL-1β values ​​of the brain tissue of sub-mouse in Examples 1, 3, 4, and 6 were significantly reduced; in addition, the degree of reduction of the IL-1β value in the brain tissue of sub-mouse in Example 6 was better than that in Examples 2 and 3.

[0155] The results showed that compared with the blank control group, the IL-1β values ​​in the brain tissue of offspring mice in the groups gavage with different doses of active folic acid substances alone and the groups gavage with different doses of 2'-fucosyllactose alone were reduced to varying degrees, among which the groups gavage with different doses of 2'-fucosyllactose showed a trend of increasing effect with increasing doses, indicating that gavage alone had the effect of reducing inflammatory factors to a certain extent; it was unexpectedly found that after gavage with the combination of high-dose active folic acid substances and low-dose 2'-fucosyllactose, the level of reduction in IL-1β values ​​in the brain tissue of offspring mice was better than that of the single gavage effect, indicating that the combination of 2'-fucosyllactose and active folic acid substances can obtain a better effect of reducing inflammatory response.

[0156] Table 8 TNF-α detection results in brain tissue of offspring mice (pg / mg·prot)

[0157]

[0158] TNF-α is produced by microglia, and as an important cytokine, its role in the central nervous system is particularly prominent, and it participates in the growth, development and regulation of various physiological activities of the nervous system. The results of the TNF-α detection in the brain tissue of offspring mice are shown in Table 8. Compared with the control group, the TNF-α values ​​in the brain tissue of offspring mice in Examples 1, 2, 3, 4, 6, and 7 were all reduced to varying degrees, among which the TNF-α value in the brain tissue of offspring mice in Example 6 was significantly reduced; in addition, the TNF-α values ​​in the brain tissue of offspring mice in Examples 6 and 7 were lower than those in Examples 2, 3, and 4.

[0159] The results showed that compared with the blank control group, the TNF-α values ​​in the brain tissue of offspring mice in the groups gavage with different doses of active folic acid substances alone and the groups gavage with different doses of 2'-fucosyllactose alone were reduced to varying degrees, among which the groups gavage with different doses of 2'-fucosyllactose showed a trend of increasing effect with increasing doses, indicating that gavage alone had the effect of reducing inflammatory factors to a certain extent; it was unexpectedly found that after gavage with the combination of high doses of active folic acid substances and low doses of 2'-fucosyllactose, the level of reduction in TNF-α values ​​in the brain tissue of offspring mice was better than that of the single gavage effect, indicating that the combination of 2'-fucosyllactose and active folic acid substances can obtain a better effect of reducing inflammatory response.

[0160] Experimental Example 4: Nutrients regulate the intestinal flora of mice

[0161] High-throughput sequencing of bacteria in fecal samples of mother mice and offspring using 16S rDNA:

[0162] 1) Extraction of total DNA of the microbiome: The total DNA of the microbiome in feces was extracted by the cetyltrimethylammonium bromide method (CTAB method), and the quality of DNA extraction was tested by agarose gel electrophoresis. The DNA was quantified by ultraviolet spectrophotometer.

[0163] 2) PCR amplification: The V3~V4 region of bacterial 16s rDNA was selected for gene amplification and sequencing. The primer sequences are shown in Table 9 below, the PCR reaction system is shown in Table 10 below, and the PCR reaction conditions are shown in Table 11 below.

[0164] Table 9 Primer sequences

[0165]

[0166] Table 10 Reaction system

[0167]

[0168] Table 11 Reaction conditions

[0169]

[0170] 3) PCR products were purified by AMPure XT beads (Beckman Coulter Genomice, MA, USA) and quantified by Qubit (Invitrogen, USA).

[0171] 4) The purified PCR products were evaluated using the Agilent 2100 bioanalyzer (Agilent, USA) and the Illumina (Kapa Biosciences, Wobum, MA, USA) library quantification kit. The qualified library concentration was above 2 nM. The qualified libraries for sequencing were gradient diluted, mixed according to the required sequencing amount, and denatured to single strands by NaOH for sequencing. The NovaSeq 6000 sequencer was used for 2×250 bp double-end sequencing, and the corresponding reagent was the NovaSeq 6000 SP Reagent Kit (500 cycles).

[0172] 5) For the paired-end data obtained by sequencing, the sample data is first split according to the Barcode information, and the adapter and Barcode sequence are removed, and then the sequence is spliced ​​to obtain the optimized sequence. After removing the chimera sequence, OUT cluster analysis is performed, and taxonomic analysis is performed on the representative sequence of OUT. Based on the results of OUT cluster analysis, multiple diversity index analyses and sequence depth detection are performed on OUT; based on taxonomic information, colony structure statistical analysis is performed at each taxonomic level.

[0173] The levels of intestinal flora in the feces of the maternal mice were analyzed. There was no significant change in the genera Ligilactobacillus and HT002 in the maternal mice of the control group before and after intervention, but the relative contents of Akkermansia and Lactobacillus were reduced. After intervention with active folic acid and 2'-fucosyllactose, the intestinal flora of maternal mice changed significantly, specifically, the relative content of Ligilactobacillus showed a decreasing trend in most intervention groups; in the active folic acid intervention group and the high-dose active folic acid + low- and high-dose 2'-fucosyllactose groups, 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 low-dose active folic acid group, the low- and high-dose 2'-fucosyllactose group, and the high-dose active folic acid + high-dose 2'-fucosyllactose group all showed an increasing trend, 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 intestinal tract of maternal mice in 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 and 2'-fucosyllactose during pregnancy can promote the increase in the relative content of beneficial bacteria in the intestines of maternal mice.

[0174] The levels of Escherichia-Shigella in the intestines of offspring mice were as follows Figure 1 As shown, 7 days after the birth of the offspring, the content of Escherichia-Shigella in the intestinal flora of each group of mice was high, belonging to the dominant flora. After continuous breastfeeding for 3 weeks, except for Example 1, the relative abundance of Escherichia-Shigella in other groups was lower than that in the control group.

[0175] The level of Akkermansia in the intestine of offspring mice Figure 2 As shown, 7 days after the birth of the offspring, the relative abundance of Akkermansia in the intestinal flora of each group of offspring was slightly different; after continuous breastfeeding for 3 weeks, compared with the control group, the relative abundance of Akkermansia in the intestinal tract of the offspring of Examples 1, 2, 3, 4, 5, and 6 increased to varying degrees.

[0176] The level of Bacteroides in the intestine of offspring mice Figure 3 As shown, 7 days after the birth of the offspring, the relative abundance of Bacteroides in the intestinal flora of each group of offspring was low, and there was no significant difference between the groups; after 3 weeks of continuous breastfeeding, compared with the control group, the relative abundance of Bacteroides in the intestinal tract of the offspring of Examples 2, 3, 6, and 7 was significantly increased.

[0177] The above results show that the intake of active folic acid and 2'-fucosyllactose during pregnancy can promote the content of beneficial bacteria in the intestines of offspring mice, and the combination of high-dose active folic acid and low-dose 2'-fucosyllactose has a better effect.

Claims

1. Use of a nutritional composition in preparing a food for assisting in improving the memory ability of offspring, characterized in that: The nutritional composition comprises the following essential components: active folic acid substances and fucosyllactose; and, in the nutritional composition, the mass ratio of the active folic acid substances to the fucosyllactose is (0.0001-0.0015): (0.5-10); The food plays the role of assisting in improving the memory ability of offspring when ingested by the mother, the mother being in the pregnancy and / or lactation period, and the offspring including the offspring in the fetal period and / or the offspring in the infant period and optionally the offspring in the childhood period.

2. The use according to claim 1, characterized in that The active folic acid 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, characterized in that The fucosyllactose includes 2'-fucosyllactose.

4. The use according to claim 1, characterized in that After being ingested by the mother, the food helps improve the memory ability of the offspring by promoting any one or more of the development of the offspring's nervous system, maintaining the health of the offspring's nervous system, and regulating the offspring's intestinal flora.

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

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

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

8. The use according to claim 4, characterized in that The regulating the intestinal flora of the offspring includes at least one of increasing the relative abundance of Akkermansia in the offspring's intestine, increasing the relative abundance of Bacteroides in the offspring's intestine, and decreasing the relative abundance of Escherichia-Shigella in the offspring's intestine.

9. The use according to any one of claims 1 to 8, characterized in that The food is infant food, children's food, adolescent food or adult food; the adult food is pregnant woman food, parturient woman food, pregnant and postpartum woman food or middle-aged and elderly people food.

10. The use according to any one of claims 1 to 8, characterized in that The food contains any one or more of the following ingredients: plant product ingredients, animal dairy product ingredients, animal meat product ingredients, functional added ingredients and any acceptable auxiliary materials.

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