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

[0001] The present application is a divisional application of the Chinese Invention Patent Application No. 202411884795.7, filed on December 20, 2024, with the title of "Use of a nutritional composition for assisting in improving memory capacity". TECHNICAL FIELD

[0002] The present application belongs to the field of food, and particularly relates to the use of a nutritional composition for assisting in improving memory capacity, and more particularly to the application of a nutritional composition for assisting in improving memory capacity of offspring through mother-to-child transmission. BACKGROUND

[0003] The development of human brain starts at 2-3 weeks of pregnancy, and the basic structure of the brain has been established, and the main compartments of the central and nerve terminal systems have been established at the end of the embryonic period (8 weeks of pregnancy). In the first 1000 days of life, brain tissue grows rapidly, and the growth rate during this period is the highest in the entire life cycle. The brain development during the pregnancy and infancy lays the foundation for cognitive, learning, memory, motor, and social-emotional skills during childhood and adulthood.

[0004] The nutritional environment in the early life can have a profound impact on brain development, and the nutrition during pregnancy plays a crucial role in the entire fetal development process. However, existing researches mainly focus on nutritional intervention from the infant stage, and there are few studies on nutritional intervention from the pregnancy stage to improve various aspects of brain development of offspring.

[0005] Folic acid is a B-vitamin that the human body cannot synthesize itself and must be obtained through additional intake. Folic acid is reduced to tetrahydrofolic acid with physiological activity by folic acid reductase, which acts as a coenzyme of the one-carbon unit transferase system in the body, plays a role in transferring one-carbon units, and further participates in important physiological activities such as nucleic acid synthesis, amino acid metabolism, hemoglobin synthesis, and synthesis of important methyl compounds. Folic acid deficiency can cause obstacles in deoxyribonucleic acid synthesis, and affect cell division and reproduction. Folic acid deficiency can also cause placental dysplasia in pregnant women, leading to spontaneous abortion, intrauterine growth retardation of the fetus, premature birth, and low birth weight of the newborn. In the process of folic acid utilization in the body, methylenetetrahydrofolate reductase (MTHFR) plays an important role, and mutations in the gene that determines the synthesis of the enzyme can lead to corresponding diseases. MTHFR C667T has three genotypes of CC, CT, and TT, with corresponding enzyme activities of 100%, 65%, and 30%, respectively. The TT genotype can greatly reduce the absorption and utilization rate of supplemented synthetic folic acid. 6S-5-methyltetrahydrofolate, also known as active folic acid, is the most active form of folic acid formed after folic acid enters the human body, and can be directly absorbed and utilized by the human body, and is not affected by the genotype of methylenetetrahydrofolate reductase in the body.

[0006] At present, there are studies on active folic acid substances in assisting to improve memory and other brain or neural development related aspects. For example, reference document 1 (CN109288005B) discloses a composition, the components of which include folic acid compounds, algal oil DHA powder, nervonic acid and N-acetylneuraminic acid, wherein the folic acid compounds are one or more of folic acid, formyltetrahydrofolic acid, 6S-5-methyltetrahydrofolic acid, L-methylfolic acid, pharmaceutically acceptable salts of folic acid, active metabolites of folic acid or pharmaceutically acceptable salts of folic acid, and substances that can be metabolized and / or generate folic acid in vivo. Studies have found that the composition has the function of assisting to improve memory.

[0007] Human milk oligosaccharides (HMOs) are a group of oligosaccharides that infants cannot digest, and are the third largest nutrients in breast milk after lactose and lipids. Human milk oligosaccharides have the effects of promoting the growth of beneficial bacteria in the intestine, reducing the adhesion of intestinal pathogenic bacteria, promoting the maturation of the small intestine and surface glycosylation, etc. According to whether there is a sialic acid residue modification, human milk oligosaccharides can be divided into two categories: neutral human milk oligosaccharides and acidic human milk oligosaccharides. Among them, neutral human milk oligosaccharides can be further divided into fucosylated human milk oligosaccharides and non-fucosylated human milk oligosaccharides according to whether there is a fucose residue in the structure. The content of neutral human milk oligosaccharides in breast milk accounts for more than 70%, and the content of fucosylated human milk oligosaccharides in breast milk is 35%-50%. The concentration of human milk oligosaccharides in breast milk shows dynamic changes during lactation, and fucosylated human milk oligosaccharides show different change patterns during lactation. 2'-fucosyllactose is the main fucosylated human milk oligosaccharide, and its concentration shows a gradual downward trend as the lactation period extends. The contents of other neutral human milk oligosaccharides (such as LNT, LNnT, LNFP I and LNFP V, etc.) show a downward trend as a whole although there is certain fluctuation in the whole lactation period. Similarly, the two main sialylated human milk oligosaccharides (6'-SL and 3'-SL) also show a downward trend as a whole during the lactation period.

[0008] Currently, there are studies on breast milk oligosaccharides in assisting the improvement of memory and other brain or neural development-related aspects. For example, reference document 2 (CN112841317B) discloses a nutritional composition comprising 20%-35% of sialylated oligosaccharides and 50%-60% of fucosylated neutral oligosaccharides by weight percentage, wherein 2'-fucosyllactose accounts for 25%-35%. The nutritional composition has the effect of assisting the improvement of the intestinal microecosystem and learning and memory ability of infants fed by elderly mothers, and can be used for preparing infant formula milk powder or probiotic products. Reference document 3 (Li N, Xu K, Li L, et al. Research progress on physiological functions and preparation methods of 2'-fucosyllactose [J]. Food and Fermentation Industries, 2021, 47(23): 265-271.) discloses that 2'-FL has a certain effect on brain development, neuron transmission and synapse formation, and can stimulate brain development and improve memory. Reference document 4 (Falsaperla R, Sortino V, Gambilonghi F, Vitaliti G, Striano P. Human Milk Oligosaccharides and Their Pivotal Role in Gut-Brain Axis Modulation and Neurologic Development: A Narrative Review to Decipher the Multifaceted Interplay. Nutrients. 2024 Sep 5;16(17):3009.) discloses that HMOs can enhance long-term potentiation (LTP) by acting as prebiotics in the gut and undergoing bacterial fermentation to produce metabolites that penetrate the blood-brain barrier. In the cellular environment, these metabolites (such as short-chain fatty acids) are either used as cellular metabolic fuels or stimulate protein expression, thereby amplifying synaptic strengthening and LTP, such as brain-derived neurotrophic factor and calcium / calmodulin-dependent protein kinase II.

[0009] Currently, there are many studies on breast milk oligosaccharides in promoting the healthy development of infants and young children, but most of these studies start from the nutritional intervention of infants and young children, ignoring the important role of the environment during the entire pregnancy period on the future healthy development of infants and young children. There are few studies on nutritional supplementation during pregnancy to improve the brain development of offspring. SUMMARY

[0010] Problems to be solved by the invention

[0011] Currently, there are studies on nutrients that can assist in improving brain development-related aspects such as memory, but the nutritional intervention starting point of these studies is mostly in the infant stage. However, even if nutrients are considered to be directly given to infants to benefit development and health, it does not mean that they can promote the development and health of offspring via, for example, the maternal-fetal transmission pathway under the condition of maternal intake, and currently there are few studies on nutritional intervention starting from pregnancy.

[0012] Therefore, there is still room for development for nutrients and their combinations that can regulate the maternal nutritional environment via maternal intake, especially maternal intake starting from pregnancy, to promote brain development-related aspects of their offspring.

[0013] To this end, the purpose of the present application is to provide a use of a nutritional composition that can advance the nutritional intervention window, improve the nutritional environment during pregnancy, create better nutritional conditions for multiple aspects of brain development of offspring, assist in improving the memory ability of offspring, and further improve the brain development of offspring while avoiding adverse pregnancy and childbirth.

[0014] Solution for solving the problem

[0015] The present application provides a use of a nutritional composition in the preparation of a foodstuff that, via intake by a mother who is in a pregnancy and / or lactation period, exerts a beneficial effect on brain development of an offspring who is in a fetal and / or infant period.

[0016] Specifically, the present application provides the following technical solutions:

[0017] [1]. A use of a nutritional composition in the preparation of a foodstuff that assists in improving the memory ability of an offspring, wherein,

[0018] The nutritional composition comprises the following essential components: an active folic acid substance and a fucosyllactose; and, in the nutritional composition, the mass ratio of the active folic acid substance to the fucosyllactose is (0.0001-0.0015):(0.5-10);

[0019] The foodstuff exerts the effect of assisting in improving the memory ability of the offspring via intake by a mother who is in a pregnancy and / or lactation period, and the offspring includes an offspring in a fetal period and / or an offspring in an infant period and optionally an offspring in a childhood period.

[0020] [2]. The use according to [1], wherein,

[0021] The active folic acid substance includes at least one of 6S-5-methyltetrahydrofolate, 6S-5-methyltetrahydrofolate calcium, and 6S-5-methyltetrahydrofolate glucosamine.

[0022] [3]. The use according to [1] or [2], wherein,

[0023] The fucosyllactose comprises 2'-fucosyllactose.

[0024] [4]. The use according to any one of [1] to [3], wherein,

[0025] The foodstuff aids in improving memory capacity of an offspring via any one or more of promoting neural system development of the offspring, maintaining neural system health of the offspring, and modulating gut microbiota of the offspring after the foodstuff is ingested by a mother.

[0026] [5]. The use according to [4], wherein,

[0027] The promoting neural system development of the offspring comprises increasing the content of brain-derived neurotrophic factor in brain tissue of the offspring.

[0028] [6]. The use according to [4] or [5], wherein,

[0029] The maintaining neural system health of the offspring comprises reducing inflammatory response in brain tissue of the offspring.

[0030] [7]. The use according to [6], wherein,

[0031] The reducing inflammatory response in brain tissue of the offspring comprises reducing the content of IL-1β and / or TNF-α in brain tissue of the offspring.

[0032] [8]. The use according to any one of [4] to [7], wherein,

[0033] The modulating gut microbiota of the offspring comprises at least one of increasing relative abundance of Akkermansia in gut of the offspring, increasing relative abundance of Bacteroides in gut of the offspring, and reducing relative abundance of Escherichia-Shigella in gut of the offspring.

[0034] [9]. The use according to any one of [1] to [8], wherein,

[0035] The foodstuff is an infant foodstuff, a child foodstuff, an adolescent foodstuff, or an adult foodstuff; and the adult foodstuff is a pregnant woman foodstuff, a lying-in woman foodstuff, a pregnant and lying-in woman foodstuff, or an elderly foodstuff.

[0036]

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

[0037] The food contains any one or more of the following ingredients: a plant product ingredient, an animal milk product ingredient, an animal meat product ingredient, a functional additive ingredient, and any acceptable adjuvant.

[0038] Effects of the invention

[0039] Through implementation of the above technical solution, the present application has the following technical effects:

[0040] The present application has found through a large number of studies that starting to supplement active folic acid substances, fucosyllactose or a combination of active folic acid substances and fucosyllactose during the gestation period of a mother can promote the nervous system development of offspring, for example, increase the content of brain-derived neurotrophic factor in the brain tissue of offspring, through, for example, the maternal-fetal transmission pathway, and can maintain the nervous system health of offspring by reducing the inflammatory response in the brain tissue of offspring, for example, reducing the content of inflammatory factors IL-1β and / or TNF-α in the brain tissue of offspring, while also promoting the intestinal flora of offspring to develop in a beneficial direction to improve the gut-brain axis regulation of offspring, thereby producing an auxiliary improvement effect on the memory ability of offspring. In particular, when the mother starts to supplement active folic acid substances and fucosyllactose in a certain proportion during the gestation period, the above effects are more optimal, thereby further significantly assisting in improving the memory ability of offspring. BRIEF DESCRIPTION OF DRAWINGS

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

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

[0043] Figure 3: Statistical results of changes in Bacteroides in the feces of the offspring mice under the intervention of different substances; among them, 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, 3 weeks after the birth of the offspring mice. DETAILED DESCRIPTION

[0044] The embodiments of the present application will be described below, 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.

[0045] I. Definition of Terms

[0046] In the present application, the numerical range indicated by "numerical value A ~ 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 values A and B.

[0047] In the present application, the meaning indicated by "may" includes both the meaning of performing a certain process and the meaning of not performing a certain process.

[0048] 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.

[0049] 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".

[0050] In the present application, the term "comprise", "have", "include" or "contain" can mean inclusive or open-ended and does not exclude additional, unrecited elements or method steps. At the same time, "comprise", "have", "include" or "contain" can also mean closed, excluding additional, unrecited elements or method steps.

[0051] In the present application, the term "about" is used to define the numerical range and parameters of the present application as approximate numerical values, and the specific relevant numerical values have been presented as accurately as possible. Unless otherwise explicitly stated, it should be understood that all ranges, quantities, numerical values and percentages used in the present application are modified by "about". Here, "about" generally means that the actual numerical value is within ±5%, ±3%, ±1% or ±0.5% of a certain numerical value or range.

[0052] In the present application, "room temperature" means an indoor ambient temperature of 23 ± 2°C.

[0053] 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" should be interpreted broadly and encompasses both raw milk (i.e. the liquid obtained directly from the mammary glands) and standardized dairy products.

[0054] In the present application, "gestation period" and "pregnancy" are used interchangeably to designate the period from conception to delivery.

[0055] In the present application, "lactation period" designates the period starting from the beginning of breastfeeding after delivery to the cessation of breastfeeding.

[0056] In the present application, "exclusively breastfed" means that the vast majority (at least 90%, preferably at least 95%, more preferably at least 98%) of the nutrients and / or energy ingested by the offspring originates from breast milk.

[0057] 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.

[0058] In the present application, "infants" designates the human group under the age of 36 months.

[0059] In the present application, "infants" designates the human group under the age of 12 months.

[0060] In the present application, "young children" designates the human group between the age of 13 and 36 months.

[0061] In the present application, "children" designates the human group older than 3 years and younger than 12 years, in the growth and development period.

[0062] In the present application, "adolescents" designates the human group older than or equal to 12 years and younger than 18 years.

[0063] In the present application, "adults" designates the human group older than or equal to 18 years.

[0064] In the present application, "elderly" designates the human group older than 45 years.

[0065] 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.

[0066] II. Nutritional composition

[0067] The present application provides a nutritional composition comprising essential components: active folate and fucosyl lactose; and, in the nutritional composition, the mass ratio of the active folate to the fucosyl lactose is (0.0001-0.0015):(0.5-10). The active folate in the present application is selected from 6S-5-methyltetrahydrofolic acid and salts thereof.

[0068] In the research process of the present application, it is accidentally found that when the active folate and the fucosyl lactose are used in a certain ratio, there is a synergistic effect between them, and compared with the active folate or the fucosyl lactose alone, the combination can obtain a better effect of assisting in improving the memory ability of offspring through, for example, the maternal-infant transmission pathway by the intake of the mother in the gestation period and / or the lactation period.

[0069] In some embodiments, the main effective components in the nutritional composition are the active folate and the fucosyl lactose, that is, the nutritional composition mainly relies on the active folate and the fucosyl lactose contained therein to exert a specific physiological activity function, for example, a function of assisting in improving the memory ability of offspring through, for example, the maternal-infant transmission pathway by the intake of the mother in the gestation period and / or the lactation period.

[0070] In some embodiments, the active folate in the present application includes at least one of 6S-5-methyltetrahydrofolic acid, 6S-5-methyltetrahydrofolic acid calcium, and 6S-5-methyltetrahydrofolic acid glucosamine salt.

[0071] The present application does not make special limitations on the source of the active folate described above, and typically, it can be obtained by the ordinary chemical synthesis method in the art, for example, by using folic acid and the like as raw materials, through reduction, methylation, chiral resolution, and optional salification and the like steps.

[0072] In some specific embodiments, the active folate in the present application is any one of 6S-5-methyltetrahydrofolic acid, 6S-5-methyltetrahydrofolic acid calcium, and 6S-5-methyltetrahydrofolic acid glucosamine salt.

[0073] In some more specific embodiments, considering the convenience of obtaining raw materials and the universality of consumption, the active folate in the present application is 6S-5-methyltetrahydrofolic acid calcium.

[0074] In some embodiments, the fucosyl lactose in the present application includes 2'-fucosyl lactose.

[0075] The fucosylated lactose of the present application is not particularly limited in its source, and typically, it can be synthesized by common chemical synthesis methods in the art, such as by a glycosylation reaction between a lactose acceptor and a fucosyl donor, etc.; it can also be obtained by microbial fermentation, etc., such as by using exogenously added lactose as a substrate, 5'-diphosphoguanosine disodium salt formed by the metabolic pathway of the microorganism itself as a precursor, and synthesizing 2'-fucosyl lactose under the action of fucosyltransferase.

[0076] In some specific embodiments, the fucosylated lactose of the present application is 2'-fucosyl lactose.

[0077] In some specific embodiments, the nutritional composition of the present application consists of the active folic substance and the fucosylated lactose; and, in the nutritional composition, the mass ratio of the active folic substance to the fucosylated lactose is (0.0001-0.0015):(0.5-10).

[0078] In order to obtain a more optimal effect of assisting in improving the memory ability of the offspring via the intake of the mother in the pregnancy and / or lactation period, in some preferred embodiments, in the nutritional composition provided by the present application, the mass ratio of the active folic substance to the fucosylated lactose is (0.0001-0.0015):1; for example, in the nutritional composition, the mass ratio of the active folic substance to the fucosylated lactose can be 0.0001:1, 0.0002:1, 0.0003:1, 0.0004:1, 0.0005:1, 0.0006:1, 0.0007:1, 0.0008:1, 0.0009:1, 0.0010:1, 0.0011:1, 0.0012:1, 0.0013:1, 0.0014:1, 0.0015:1, etc.; preferably (0.0003-0.0010):1; more preferably (0.0004-0.0010):1; even more preferably (0.0006-0.0010):1.

[0079] The composition of the present application is typically an artificially synthesized or compounded composition, i.e., not a natural composition such as breast milk, etc.

[0080] III. Use of the nutritional composition

[0081] The present application proposes that after the active folic acid substance and fucosyllactose are compounded, especially after being compounded in a specific ratio, the mother in the gestation period and / or lactation period can improve the memory ability of the offspring by intake, and the two substances have a synergistic effect, and the above-mentioned effect is better than that of the active folic acid substance or fucosyllactose alone. At the same time, the present application finds that the above-mentioned effect of assisting to improve the memory ability of the offspring not only exists in the fetus in the mother and the infant who eats breast milk, but also can be aimed at the infant who does not eat breast milk but is in full contact with the mother, and at the same time, this regulating effect can continue to the childhood of the offspring, and even has a lasting effect on the offspring.

[0082] Based on this, the present application provides the use of the above-mentioned nutritional composition in the preparation of food for assisting to improve the memory ability of the offspring, which plays the role of assisting to improve the memory ability of the offspring by the mother's intake, the mother is in the gestation period and / or lactation period, and the offspring includes the fetus period offspring and / or the infant period offspring and the optional childhood offspring.

[0083] In some embodiments, the present application provides the use of the above-mentioned nutritional composition in the preparation of food for assisting to improve the memory ability of the offspring, which plays the role of assisting to improve the memory ability of the offspring by the mother's intake, the mother is in the gestation period, and the offspring includes the fetus period offspring and the optional childhood offspring.

[0084] In some embodiments, the present application provides the use of the above-mentioned nutritional composition in the preparation of food for assisting to improve the memory ability of the offspring, which plays the role of assisting to improve the memory ability of the offspring by the mother's intake, the mother is in the gestation period, and the offspring includes the infant period offspring and the optional childhood offspring.

[0085] In some embodiments, the present application provides the use of the above-mentioned nutritional composition in the preparation of food for assisting to improve the memory ability of the offspring, which plays the role of assisting to improve the memory ability of the offspring by the mother's intake, the mother is in the gestation period, and the offspring includes the fetus period offspring and the infant period offspring and the optional childhood offspring.

[0086] In some embodiments, the present application provides the use of the above-mentioned nutritional composition in the preparation of food for assisting to improve the memory ability of the offspring, which plays the role of assisting to improve the memory ability of the offspring by the mother's intake, the mother is in the lactation period, and the offspring includes the infant period offspring and the optional childhood offspring.

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

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

[0089] In some embodiments, the present application provides use of the above-mentioned nutritional composition in the manufacture of a foodstuff for assisting in improving memory capacity of an offspring, said foodstuff exerting said assisting in improving memory capacity of an offspring via ingestion by a mother, said mother being in a gestation period and a lactation period, said offspring including a fetal offspring and optionally a childhood offspring.

[0090] In some embodiments, the "mother" and "offspring" of the present application include mammals, including but not limited to humans, monkeys, chimpanzees, cows, sheep, cats, dogs, horses, rabbits, mice, rats, guinea pigs, and the like.

[0091] In some embodiments, the childhood offspring of the present application can or can not be breastfed, preferably is breastfed. In some embodiments, the breastfeeding of the present application can be exclusive breastfeeding, predominant breastfeeding, or mixed breastfeeding with a small amount of breast milk and other food.

[0092] The assisting in improving memory capacity of an offspring (including promoting neural system development of an offspring, maintaining neural system health of an offspring, and modulating gut microbiota of an offspring) of the present application is not for the purpose of treating or preventing a disease.

[0093] In some embodiments, the foodstuff of the present application assists in improving memory capacity of an offspring via any one or more of promoting neural system development of an offspring, maintaining neural system health of an offspring, and modulating gut microbiota of an offspring after ingestion by a mother.

[0094] In some specific embodiments, the promoting neural system development of an offspring includes elevating the content of brain-derived neurotrophic factor in brain tissue of an offspring.

[0095] In some specific embodiments, the maintaining the neurological health of the offspring comprises reducing inflammation in the brain tissue of the offspring. In some more specific embodiments, the reducing inflammation in the brain tissue of the offspring comprises reducing the levels of IL-1 β and / or TNF-α in the brain tissue of the offspring.

[0096] In some specific embodiments, the modulating the gut microbiota of the offspring comprises at least one of increasing the relative abundance of Akkermansia in the gut of the offspring, increasing the relative abundance of Bacteroides in the gut of the offspring, and decreasing the relative abundance of Escherichia-Shigella in the gut of the offspring.

[0097] 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 neuropsychiatric diseases (such as Alzheimer's disease), and have the potential to be a therapeutic target for various neuropsychiatric diseases. At the same time, it has been found that Escherichia-Shigella is increased in the fecal samples of Alzheimer's disease patients compared to healthy people (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 decreases (Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, Soleimanpour S. A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders. Clin Microbiol Rev. 2022 Jan 19;35(1):e0033820. doi: 10.1128 / CMR.00338-20.).

[0098] The present application has found that the supplementation of the nutritional composition to the mother during the pregnancy can increase the relative abundance of Akkermansia and Bacteroides in the gut of the offspring and decrease the relative abundance of Escherichia-Shigella in the gut of the offspring. Therefore, the present application believes that the supplementation of the nutritional composition or the food containing the nutritional composition to the mother during the pregnancy and / or lactation can not only benefit the gut microbiota of the offspring, but also benefit the brain development of the offspring through the gut-brain axis regulation, and thus improve the memory ability of the offspring.

[0099] The present application does not particularly limit the food containing the nutritional composition or prepared by the nutritional composition.

[0100] In some embodiments, the food of the present application is a candy, a beverage, a dairy product, a baked food or a dietary supplement. Exemplarily, the candy includes a hard candy, a gel candy, a crisp candy, a pressed candy and an aerated candy, etc.; the beverage includes a carbonated beverage, a tea beverage, a coffee beverage, a fruit and vegetable juice beverage and a lactic acid bacteria beverage, etc.; the dairy product includes fermented milk, cheese and milk powder, etc.; the baked food includes bread, cake and biscuit, etc.; the dietary supplement includes a hard capsule, a soft capsule, a tablet, an oral liquid, a granule and a powder, etc.

[0101] In some embodiments, the food of the present application is a special dietary food; the special dietary food includes an infant formula, an infant complementary food, a complementary nutritional supplement and a special medical purpose formula, etc.

[0102] In some embodiments, the food of the present application is an infant food, a child food, an adolescent food or an adult food.

[0103] In some preferred embodiments, the food of the present application is a pregnant woman food, a postpartum woman food or a pregnant and postpartum woman food; the pregnant woman food is suitable for the pregnant women to eat, and the postpartum woman food is suitable for the postpartum women, especially the lactating women, to eat; preferably, the food is a pregnant woman formula milk powder, a postpartum woman formula milk powder or a pregnant and postpartum woman oral liquid.

[0104] In some embodiments, in the food of the present application, the mass ratio of the active folic acid substance to the fucosyl lactose is (0.0001-0.0015):(0.5-10), preferably (0.0001-0.0015):1.

[0105] The present application does not particularly limit the absolute content of the active folic acid substance and the fucosyl lactose in the food, which can meet the requirements of the local food-related laws and regulations.

[0106] In some embodiments, the addition of the nutritional composition results in the food having 6S-5-methyltetrahydrofolate in an amount of 0.0005% to 0.10%, preferably 0.0008% to 0.8%, more preferably 0.0010% to 0.75%, and 2'-fucosyllactose in an amount of 0.5% to 10%, preferably 1% to 8%, more preferably 2% to 6.5%, by mass percentage, based on the calcium 6S-5-methyltetrahydrofolate and 2'-fucosyllactose, respectively.

[0107] When the active folate and fucosyllactose are present in the food in the above ranges, and are ingested by a parent (e.g., a human (i.e., a pregnant woman) or an animal (i.e., a pregnant female)), the active folate and fucosyllactose can significantly, and particularly synergistically, assist in improving the offspring's memory, and at the same time, can also balance (other) aspects of nutrition required by the human or animal body (including the parent and the offspring).

[0108] In addition to the above-described components in the nutritional composition, the food can also contain other ingredients, such as ingredients often contained in formulae, such as formulae for pregnant and postpartum women, e.g., milk powder, such as proteins / amino acids, carbohydrates, fats, vitamins, minerals, etc.

[0109] In addition, depending on the type of food and the final needs of the target subject, 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.

[0110] For the plant product ingredients, examples can include fruits such as figs, pomegranates, kiwis, oranges, tangerines, pineapples, strawberries, apples, bananas, grapes, pears, cherries, blueberries, blackberries, blackcurrants, cranberries, raspberries, melons, emblics, and mulberries, or extracts thereof; fruit and vegetable materials such as onions, cucumbers, tomatoes, cauliflowers, red beetroots, spinach, 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, japonica, buckwheat, soybeans, fava beans, peas, mung beans, adzuki beans, kidney beans, or extracts thereof; nut materials such as walnuts, pistachios, cashews, hazelnuts, almonds, apricot kernels, pine nuts, peanuts, melon seeds, chestnuts, macadamia nuts, ginkgo nuts, or extracts thereof; coffee or extracts thereof; and some medicinal and edible plant materials or extracts thereof.

[0111] For animal milk product ingredients, examples include fresh milk derived from cows, sheep, etc., and reprocessed milk products such as whole milk powder, skim milk powder, concentrated whey protein powder, desalted whey powder, whey protein powder, hydrolyzed whey protein powder, casein powder, etc.

[0112] For animal meat product ingredients, examples include meat product ingredients of pigs, cows, sheep, aquatic species, or birds.

[0113] For functional additive ingredients, examples include vitamin supplements, mineral supplements, nucleotide supplements, dietary fibers, functional polyunsaturated fatty acid supplements, etc.

[0114] For any acceptable adjuvants, examples include solvents, antioxidants, antibacterial agents, thickening agents, diluents, co-solvents, stabilizers, emulsifiers, fillers, disintegrants, lubricants, coating materials, anti-caking agents, flavoring agents, sweeteners, food essences, food colorants, etc.

[0115] Examples

[0116] The embodiments of the present application will be described in detail below with reference to examples, but those skilled in the art will understand that the following examples are only for illustration of the present application and should not be considered as limiting the scope of the present application. If the specific conditions are not specified in the examples, the conventional conditions or the conditions recommended by the manufacturer are used. Unless otherwise specified, the materials or instruments used are commercially available conventional products that can be used.

[0117] Experimental animals and grouping used in the examples

[0118] Select 100 SPF female rats of 12 weeks of age and 100 SPF male rats of 12 weeks of age, weighing 350-410 g; purchased from Hangzhou Medical College, animal qualification certificate number 20240318Aazz0100000597, production license number: SCXK (Zhejiang) 2024-002. Raising conditions: animals were raised in a barrier environment, indoor temperature 24±2℃, humidity 45±5%, animals were free to drink water, 12h light and dark alternating environment feeding per day. This experiment was approved by the animal ethics committee of Southeast University, ethics number: 20240316003.

[0119] After 3 days of adaptive feeding, female and male rats were caged together in a 1:1 ratio, and the female rats were given intragastrical intervention starting from the appearance of vaginal plugs, and the female rats were continuously given intragastrical intervention until the offspring rats were weaned after 3 weeks. The experimental group was given the corresponding dose of sample aqueous solution according to the animal grouping, and the control group was given the corresponding dose of normal saline. Intragastrical administration was performed once a day, and the experiment lasted for 6 weeks. Each dose was given a maintenance feed. The low and high doses of active folic acid substances (6S-5-methyltetrahydrofolic acid calcium) were 5.3 and 10.1 (μg / d / each), and the low and high doses of 2'-fucosyllactose were 12.6 and 37.8 (mg / d / each). The specific doses of each group are shown in Table 1 below. After the end of intragastrical administration, the indicators of the offspring rats were monitored.

[0120] Table 1: Intragastrical dose of experimental animals

[0121]

[0122] Instruments, consumables and reagents used in the examples

[0123] The main consumables, reagents and experimental instruments used in the experiment are shown in Tables 2 and 3.

[0124] Table 2: Main experimental consumables and reagents

[0125]

[0126] Table 3: Main experimental instruments

[0127]

[0128] Example 1: Nutritional substances improve the learning and memory ability of offspring rats

[0129] The Morries water maze experiment is mainly used to test the learning and memory ability of experimental animals to spatial position and orientation (spatial orientation), and is widely used in scientific research fields such as learning and memory, intelligence and aging, and is widely recognized in the world. It is a classic experiment of behavior science, especially learning and memory research.

[0130] After the offspring rats were weaned and separated from the mother rats, the offspring rats were placed in the pool for free swimming for 2 min to familiarize them with the maze environment. A fixed time period was set each day, and 4 times of training were performed in each time period. At the beginning of training, the platform was placed in the first quadrant. The offspring rats were placed in the pool from any of the four starting points on the pool wall, facing the pool wall, and the time for the offspring rats to find the platform (escape latency) and swimming path were recorded. If the offspring rats found the platform or failed to find the platform within 90 s, the experimenter would take them to the platform and rest on the platform for 15 s before the next experiment. The average value of the 4 training latencies of the offspring rats each day was taken as the learning score of the offspring rats on that day, and the positioning navigation experiment lasted for 4 days.

[0131] The platform was removed at the same time period on day 5, and the pups were fixed in the fourth quadrant to enter the water, and the video recorded the residence time of the pups in the original platform quadrant within 60s and the number of times passing through the original platform position. If the residence time of the animals in the original platform quadrant is longer and the number of times passing through the original platform position is more, it indicates that the long-term memory of the animals to the platform position is better.

[0132] The stability of water temperature and environmental conditions in the maze was maintained, the training was performed at a fixed time every day, the light around the maze and the reference signs were kept clear and unchanged, at the end of each experiment, the surface water of the pups was wiped dry, the bedding was replaced to keep the feeding environment dry, and the pups were fed freely in the barrier environment.

[0133] The Super Maze software was used to process the video files of the pups in the water maze, and the swimming tracks of the pups in the water maze were recorded and analyzed.

[0134] Table 4: Number of times of platform crossing of pups

[0135]

[0136] The more times the animals pass through the original platform position, the better the long-term memory of the animals to the platform position. The results in Table 4 show that, compared with the control group, the number of times of platform crossing of the pups in examples 1, 2, 3, 4, 5, 6 and 7 is increased to different degrees, and the number of times of platform crossing of the pups in examples 3, 4, 5, 6 and 7 is significantly increased; in addition, the number of times of platform crossing of the pups in examples 5, 6 and 7 is increased to different degrees compared with examples 1, 2, 3 and 4.

[0137] The results show that, compared with the blank control group, the number of times of platform crossing of the pups in the different dose groups of active folic acid alone and the different dose groups of 2'-fucosyllactose alone is increased and shows a trend of increasing with the increase of the dose; it is unexpectedly found that the number of times of platform crossing of the pups after gavage of the combination of active folic acid and 2'-fucosyllactose is higher than that of the single gavage, and the combination of the low-dose group of active folic acid and the low-dose group of 2'-fucosyllactose has a better effect on promoting the spatial memory of the pups.

[0138] Table 5: Platform residence time of pups (s)

[0139]

[0140] The longer the animal stays in the quadrant where the platform is located, the better the long-term memory of the animal to the platform location. As shown in Table 5, relative to the control group, the platform stay time of the sub-mice of Examples 1, 2, 3, 4, 5, 6, and 7 all increased to different degrees, among which the platform stay time of the sub-mice of Examples 1, 4, 5, 6, and 7 increased significantly; in addition, the platform stay time of the sub-mice of Examples 5, 6, and 7 was higher than that of Examples 1, 2, and 3.

[0141] The results show that, compared with the blank control group, the platform stay time of the sub-mice of the different dose groups of the active folic acid substance and the different dose groups of 2'-fucosyllactose alone increased, among which the different dose groups of 2'-fucosyllactose showed a trend of increasing effect with increasing dose; it was unexpectedly found that the platform stay time of the sub-mice after being administered with the combination of the low dose and the high dose of the active folic acid substance and the low dose of 2'-fucosyllactose was higher than that of the single administration effect, and the combination of the high dose of the active folic acid substance and the low dose of 2'-fucosyllactose had a better effect on promoting the spatial memory of the sub-mice.

[0142] Experimental Example 2: Nutritional substances promote the development of the nervous system of sub-mice

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

[0144] The detection of brain-derived neurotrophic factor (BDNF) in the brain tissue of sub-mice was performed using a full-automatic enzyme marker, and the content of brain-derived neurotrophic factor in the brain tissue of sub-mice was detected according to the brain-derived neurotrophic factor enzyme-linked immunoassay (Elisa) method.

[0145] Table 6: Detection results of brain-derived neurotrophic factor in the brain tissue of sub-mice (ng / mg·prot)

[0146]

[0147] Brain-derived neurotrophic factor is a protein molecule that has the functions of maintaining nerve cell survival, differentiation induction, promoting maturation, and regulation, is expressed in nerve cells under physiological conditions, and is elevated through excitatory neurotransmission. As shown in Table 6, relative to the control group, the content of brain-derived neurotrophic factor in the brain tissue of the sub-mice of Examples 1, 2, 3, 4, 5, 6, and 7 all increased to different degrees; in addition, the content of brain-derived neurotrophic factor in the brain tissue of the sub-mice of Example 7 was higher than that of Examples 2 and 4, respectively.

[0148] The results show that compared with the blank control group, the brain tissue-derived neurotrophic factor content of the offspring mice in the active folic acid substance alone gavage different dose group and the 2'-fucosyllactose alone gavage different dose group is improved to different degrees, indicating that the single gavage has a certain degree of promoting effect on the promotion of brain tissue-derived neurotrophic factor content; it is accidentally found that the brain tissue-derived neurotrophic factor content of the offspring mice in the combination of active folic acid substance high dose and 2'-fucosyllactose high dose group is higher than that of single gavage, indicating that the combination of 2'-fucosyllactose and active folic acid substance can obtain better effect of promoting the development of nervous system.

[0149] Experimental Example 3: Nutritional substances maintain the health of the nervous system of offspring mice

[0150] After the brain tissue is thawed, it is rinsed in a 4°C pre-cooled physiological saline solution to remove blood, and after the residual physiological saline solution in the brain tissue is absorbed with filter paper, it is accurately sampled and weighed, 1:10 PBS solution (0.1 g of tissue is added to 0.9 mL of PBS solution) is added, and a 10% homogenate is prepared using a homogenizer. The homogenate is used to detect inflammatory factors.

[0151] (1) The detection of interleukin IL-1β (Interleukin-1β, IL-1β) in the brain tissue of offspring mice is carried out using a full-automatic enzyme marker, and the IL-1β content in the brain tissue of offspring mice is detected according to the IL-1β enzyme-linked immunoassay Elisa method.

[0152] (2) The detection of tumor necrosis factor α (Tumor necrosis factor-α, TNF-α) in the brain tissue of offspring mice is carried out using a full-automatic enzyme marker, and the TNF-α content in the brain tissue of offspring mice is detected according to the TNF-α enzyme-linked immunoassay Elisa method.

[0153] Table 7: Results of IL-1β detection in the brain tissue of offspring mice (pg / mg·prot)

[0154]

[0155] Studies have shown that IL-1 is produced by mononuclear, endothelial, fibroblastic or other cells in response to inflammatory reactions, plays an important role in immune response and tissue repair, and is involved in neuroprotection, tissue remodeling and repair. IL-1β is an effective pro-inflammatory cytokine mainly secreted by lymphocytes, macrophages and monocytes. When there is viral infection or inflammation, the expression of pattern recognition receptors (PRRs) and Toll-like receptors (TLRs) increases, leading to increased expression of IL-1β. The results of IL-1β detection in the brain tissue of the sub-mice in Table 7 show that, compared with the control group, the IL-1β values in the brain tissue of the sub-mice in Examples 1, 2, 3, 4, 6, 7 are reduced to different degrees, among which the IL-1β values in the brain tissue of the sub-mice in Examples 1, 3, 4, 6 are significantly reduced; in addition, the degree of reduction of the IL-1β value in the brain tissue of the sub-mice in Example 6 is better than that in Examples 2 and 3.

[0156] The results show that, compared with the blank control group, the IL-1β values in the brain tissue of the sub-mice in the different dose groups of active folic acid alone and the different dose groups of 2'-fucosyllactose alone are reduced to different degrees, among which the different dose groups of 2'-fucosyllactose alone show a trend of increasing effect with increasing dose, indicating that the single administration of both has a certain degree of effect on reducing inflammatory factors; it is unexpectedly found that the IL-1β values in the brain tissue of the sub-mice after administration of the combination of high-dose active folic acid and low-dose 2'-fucosyllactose are all better than the single administration effect, indicating that the combination of 2'-fucosyllactose and active folic acid can achieve a better effect of reducing inflammatory response.

[0157] Table 8 Detection results of TNF-α in the brain tissue of sub-mice (pg / mg·prot)

[0158]

[0159] TNF-α is produced by microglial cells and acts as an important cytokine, especially in the central nervous system, which is involved in the regulation of growth, development and various physiological activities of the nervous system. The detection results of TNF-α in the brain tissue of sub-mice are shown in Table 8. Compared with the control group, the TNF-α values in the brain tissue of sub-mice in Examples 1, 2, 3, 4, 6, 7 are reduced to different degrees, among which the TNF-α value in the brain tissue of sub-mice in Example 6 is significantly reduced; in addition, the TNF-α values in the brain tissue of sub-mice in Examples 6 and 7 are lower than those in Examples 2, 3 and 4.

[0160] Results showed that: compared with the blank control group, the TNF-α values of the brain tissues of the offspring mice in the active folic acid substance alone and 2'-fucosyllactose alone groups were reduced to different degrees, and the effect of the 2'-fucosyllactose group showed a trend of increasing with the increase of the dose, indicating that the single administration of the two had a certain degree of effect on reducing inflammatory factors; it was unexpectedly found that the TNF-α values of the brain tissues of the offspring mice in the active folic acid substance high dose plus 2'-fucosyllactose low dose group were reduced to a higher level than that of the single administration, indicating that the combination of 2'-fucosyllactose and active folic acid substance could obtain a better effect of reducing inflammatory response.

[0161] Experimental Example 4: Nutritional substances regulate the intestinal flora of offspring mice

[0162] High-throughput sequencing of bacteria in the fecal samples of the mother mice and offspring mice was performed by 16S rDNA:

[0163] 1) Microbiome total DNA extraction: The total microbiome total DNA in the feces was extracted by 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.

[0164] 2) PCR amplification: The V3~V4 region of bacterial 16s rDNA was selected for gene amplification and sequencing, the primer sequence was shown in Table 9, the PCR reaction system was shown in Table 10, and the PCR reaction conditions were shown in Table 11.

[0165] Table 9 Primer sequence

[0166]

[0167] Table 10 Reaction system

[0168]

[0169] Table 11 Reaction conditions

[0170]

[0171] 3) The PCR product was purified by AMPure XT beads (Beckman Coulter Genomice, MA, USA), and quantified by Qubit (Invitrogen, USA).

[0172] 4) The purified PCR products were evaluated using an Agilent 2100 Bioanalyzer (Agilent, USA) and Illumina (Kapa Biosciences, Wobum, MA, USA) library quantification kit. The qualified library concentration was above 2 nM. The qualified sequencing library was gradient diluted, mixed according to the required sequencing amount, and denatured into single-stranded by NaOH for sequencing. The NovaSeq 6000 sequencer was used for 2x250 bp double-end sequencing, and the corresponding reagent was NovaSeq 6000 SP Reagent Kit (500 cycles).

[0173] 5) The double-end data obtained by sequencing was first split according to the Barcode information, and the adapter and Barcode sequences were removed, then the sequence was spliced to obtain the optimized sequence. After removing the chimeric sequence, OUT clustering analysis was performed, and the OUT representative sequence was analyzed taxonomically. Based on the OUT clustering analysis results, various diversity index analysis and sequence depth detection were performed on the OUT; based on the taxonomic information, statistical analysis of the colony structure was performed at each taxonomic level.

[0174] The mother mouse fecal intestinal flora genus level was analyzed. The relative content of Akkermansia and Lactobacillus in the control group did not change significantly before and after intervention, but the relative content of Akkermansia and Lactobacillus decreased. After the intervention of active folic acid and 2'-fucosyllactose, the intestinal flora of the mother mouse changed greatly, specifically, the relative content of Lactobacillus in most intervention groups showed a decreasing trend; in the active folic acid intervention group and the active folic acid high dose + 2'-fucosyllactose low dose group, the relative abundance of Akkermansia increased, and the relative content was higher than that of the control group; after delivery, the relative content of Lactobacillus in the active folic acid low dose group, 2'-fucosyllactose low dose group and active folic acid high dose + 2'-fucosyllactose high dose group 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 mother mouse intestinal tract of Examples 1, 2, 3, 6 and 7 increased and was higher than that of the control group. The results showed that the intake of a certain dose of active folic acid and 2'-fucosyllactose during pregnancy can promote the increase of the relative content of beneficial bacteria in the mother mouse intestinal tract.

[0175] The levels of Escherichia-Shigella in the intestines of baby mice were as follows: Figure 1 As shown, 7 days after birth, the intestinal flora of mice in all groups showed a high content of Escherichia-Shigella, which was the dominant flora. After 3 weeks of continuous breastfeeding, except for Example 1, the relative abundance of Escherichia-Shigella in all other groups was lower than that in the control group.

[0176] Akkermansia levels in the intestines of baby mice as follows Figure 2 As shown, 7 days after birth, the relative abundance of Akkermansia in the intestinal flora of mice in each group was relatively similar; after 3 weeks of continuous breastfeeding, compared with the control group, the relative abundance of Akkermansia in the intestines of mice in groups 1, 2, 3, 4, 5 and 6 of Examples all increased to varying degrees.

[0177] The level of Bacteroides in the intestines of offspring mice is as follows Figure 3 As shown, 7 days after birth, the relative abundance of Bacteroides in the gut microbiota of the offspring mice in each group was low, with no significant difference between the groups; after 3 weeks of continuous breastfeeding, compared with the control group, the relative abundance of Bacteroides in the gut microbiota of offspring mice in groups 2, 3, 6 and 7 of Examples was significantly increased.

[0178] In summary, the results show that intake of active folic acid and 2'-fucosylated lactose during pregnancy promotes the content of beneficial bacteria in the intestines of offspring mice, and the combination of high dose of active folic acid and low dose of 2'-fucosylated lactose has the better effect.

Claims

1. The use of a nutritional composition in the preparation of a food that promotes the development of the nervous system in offspring and helps improve the nervous system health of offspring, characterized in that, The nutritional composition comprises the following essential components: active folic acid and fucoidan; and in the nutritional composition, the mass ratio of the active folic acid to the fucoidan is (0.0001~0.0015):

1. The active folic acid substance includes at least one of 6S-5-methyltetrahydrofolate, calcium 6S-5-methyltetrahydrofolate, and glucosamine 6S-5-methyltetrahydrofolate; the fucoidyl lactose includes 2'-fucosylation lactose. The food exerts its effect of assisting in improving the neurological health of offspring through maternal ingestion, wherein the mother is continuously pregnant and lactating, and the offspring include fetal offspring and / or infant offspring and optionally childhood offspring. The promotion of offspring's nervous system development includes increasing the levels of brain-derived neurotrophic factor in offspring brain tissue, and the improvement of offspring's nervous system health includes reducing inflammatory responses in offspring brain tissue.

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

3. The use according to claim 1 or 2, characterized in that, The food products are infant food, children's food, adolescent food, or adult food; the adult food products are food for pregnant women, postpartum women, pregnant and postpartum women, or middle-aged and elderly people.

4. The use according to claim 1 or 2, characterized in that, The food contains any one or more of the following ingredients: plant-based ingredients, animal dairy ingredients, animal meat ingredients, functional additives, and any acceptable excipients.

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