Use of human milk oligosaccharide for improving intestinal flora of mother and infant

Abstract

The use of a human milk oligosaccharide in the preparation of a food product which contributes to the regulation of the intestinal flora of a mother and her offspring via ingestion by the mother. The human milk oligosaccharide is 2'-fucosyllactose. The mother is in the period of pregnancy and / or nursing. The contribution to the regulation of the intestinal flora of the offspring comprises at least one of increasing the relative abundance of Lactobacillus HT002 in the intestinal tract of the offspring, increasing the relative abundance of Akkermansia in the intestinal tract of the offspring, increasing the relative abundance of Clostridia_UCG-014_unclassified in the intestinal tract of the offspring, and increasing the relative abundance of Bacteroides in the intestinal tract of the offspring.

Description

Uses of human milk oligosaccharides in improving maternal and infant gut microbiota Technical Field

[0001] This invention belongs to the field of nutritional research. This invention relates to the use of human milk oligosaccharides to improve the intestinal flora of mothers and infants, specifically the use of 2'-fucosylated lactose to improve the intestinal flora of mothers and infants. Background Technology

[0002] In recent years, the gut microbiota, often referred to as the body's second brain, has been extensively studied. Numerous studies have found a close relationship between the gut microbiota and human health, with studies confirming the existence of axes such as the gut-brain axis, liver-gut axis, gut-kidney axis, gut-skin axis, and gut-fat axis. As a barometer of human health, the gut microbiota directly affects the body's metabolic, immune, and nervous systems. The gut microbiota is influenced by various factors, including diet, age, lifestyle, medications, antibiotic use, and disease states; different populations and individuals have different gut microbiota. The human gut microbiota originates from the mother. Infants not only receive genetic material from their mothers but also from their mothers' blood. Furthermore, mothers pass on a type of bacteria called the "microbial community" directly to the fetus, which are beneficial bacteria passed directly from mother to newborn. Studies have also shown that some Lactobacillus and Bifidobacterium microorganisms can enter the bloodstream, migrate to the mammary glands, and be passed on to infants.

[0003] To regulate gut microbiota and promote human health, dietary supplements containing edible probiotics are often chosen. However, for some probiotics that cannot be consumed directly, their relative abundance in the gut cannot be increased directly through exogenous supplementation. Therefore, promoting the proliferation of these probiotics through exogenous intake of other substances is an alternative way to increase their abundance in the gut.

[0004] Probiotics that are not currently suitable for direct consumption include Akkermansia muciniphila, a Gram-negative anaerobic bacterium that primarily colonizes the mucus layer in the gastrointestinal tract, protecting the mucus layer and connective tissue (Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen.nov.,sp.nov.,a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004 Sep; 54(Pt5):1469-1476. doi:10.1099 / ijs.0.02873-0.). Akkermansia muciniphila, as a new generation of probiotics, is a biomarker of health (Zhang T, Li Q, Cheng L, Buch H, Zhang F. Akkermansia muciniphila is a promising probiotic. Microb Biotechnol. 2019 Nov; 12(6):1109-1125. doi:10.1111 / 1751-7915.13410.). Studies have shown that Akkermansia microorganisms play an important probiotic role in metabolic diseases (such as diabetes, obesity, etc.) and intestinal diseases (such as inflammatory bowel disease, ulcerative colitis, etc.).

[0005] Human milk oligosaccharides (HMOs) are a group of oligosaccharides that infants cannot digest, and are the third most abundant nutrient in breast milk after lactose and lipids. HMOs promote the growth of beneficial intestinal bacteria, reduce the adhesion of pathogenic bacteria, promote small intestinal maturation, and promote surface glycosylation. Based on the presence or absence of sialic acid residue modifications, HMOs can be divided into two main categories: neutral human milk oligosaccharides and acidic human milk oligosaccharides. Neutral human milk oligosaccharides can be further classified according to the presence or absence of fucose residues in their structure into fucosylated human milk oligosaccharides and non-fucosylated human milk oligosaccharides. Neutral human milk oligosaccharides account for more than 70% of the content in breast milk, while fucosylated neutral human milk oligosaccharides account for 35%–50%. Numerous studies have shown that the concentration of HMOs in breast milk exhibits dynamic changes during lactation. 2'-Fucosyllactose (2'-FL) is the most abundant human milk oligosaccharide in breast milk, and its concentration decreases with the extension of lactation time. The contents of other neutral HMOs (such as lactose-N-tetrasaccharide (LNT), lactose-N-neotetrasaccharide (LNnT), lactose-N-fucopentose I (LNFP I), and lactose-N-fucopentose V (LNFP V)) fluctuate to some extent throughout lactation, but also show an overall decreasing trend.

[0006] Studies have shown that HMOs in breast milk can regulate the gut microbiota of infants. For example, reference 1 (CN107847509B) discloses a nutritional composition containing at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, which can be used in infant formula to regulate the gut microbiota of infants and induce a gut microbiota similar to that of breastfed infants. Reference 2 (CN115836733A) discloses the application of oligosaccharides, such as 2'-fucosylvose or a combination of fructooligosaccharides, galactooligosaccharides and 2'-fucosylvose, in the preparation of products that regulate gut microbiota. The regulation of gut microbiota includes inhibiting the adhesion ability of pathogenic bacteria and / or improving the competitive adhesion antibacterial ability of Lactobacillus rhamnosus and / or improving the repulsive adhesion antibacterial ability of Lactobacillus rhamnosus. Reference 3 (CN116548624A) discloses a protein oligosaccharide composition for improving the gut health of infants and young children. The composition includes osteopontin and 2'-fucosylated lactose. The improvement of gut health in infants and young children also includes regulating the production of short-chain fatty acids, regulating the rate of gas production, reducing ammonia production, and / or improving the composition and diversity of gut microbiota. Summary of the Invention

[0007] The problem the invention aims to solve

[0008] Existing research has found that an infant's gut microbiota initially originates from the mother's gut microbiota. A healthy maternal gut microbiota can pass on a better microbiota to the offspring and influence the establishment of the offspring's microbiota, laying a good foundation for a healthy offspring microbiota. Therefore, this invention suggests that improving the microbiota from the source—that is, intervening during pregnancy to enhance the health of the mother during pregnancy and lactation, thereby regulating the offspring's microbiota and improving the offspring's health—is more beneficial than intervening after birth.

[0009] However, most existing research focuses on interventions during infancy, such as developing more nutritionally complete infant formula or providing more infant nutritional supplements. There is a lack of research on interventions starting from pregnancy to regulate the offspring's gut microbiota towards a beneficial direction. For example, there are no reports on studies that can further increase the abundance of beneficial bacteria and suppress the abundance of pathogenic bacteria in the offspring's gut by increasing the abundance of beneficial bacteria and suppressing the abundance of pathogenic bacteria in the mother's gut during pregnancy and lactation. There are also few reports on the exploration of substances that can regulate the gut microbiota of the mother during pregnancy and lactation and simultaneously regulate the gut microbiota of the offspring.

[0010] In response, this invention unexpectedly discovered through research that mothers who take 2'-fucosylated lactose during pregnancy can significantly improve their gut microbiota and simultaneously improve the gut microbiota of their offspring. 2'-fucosylated lactose can promote the increase of beneficial bacteria in the gut of pregnant and lactating mothers and reduce the relative content of pathogenic bacteria, while increasing the content of probiotics in the gut of their offspring and inhibiting the relative abundance of pathogenic bacteria in the gut of their offspring.

[0011] Therefore, the object of the present invention is to provide the use of human milk oligosaccharides, particularly 2'-fucosylated lactose, for non-therapeutic purposes in simultaneously regulating the gut microbiota of pregnant and / or lactating mothers and their offspring. Furthermore, the object of the present invention is to provide the use of human milk oligosaccharides, particularly 2'-fucosylated lactose, in the preparation of foods which, when ingested by the mother, help to regulate the gut microbiota of the mother and her offspring.

[0012] Solution for solving the problem

[0013] The present invention has found that the above-mentioned technical problems can be solved by the following solution:

[0014] [1]. Use of human milk oligosaccharides in the preparation of foods which, when ingested by the mother, help to regulate the gut microbiota of the mother and her offspring, wherein the human milk oligosaccharide is 2'-fucosylated lactose, and the mother is pregnant and / or lactating;

[0015] The gut microbiota regulation that helps to regulate offspring includes at least one of the following: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, and increasing the relative abundance of Bacteroides in the offspring gut.

[0016] [2]. According to the use described in [1], the method of helping to regulate the gut microbiota of pregnant mothers includes at least one of the following: increasing the relative abundance of Akkermansia in the gut of pregnant mothers, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of pregnant mothers, increasing the relative abundance of Ligilactobacillus in the gut of pregnant mothers, and decreasing the relative abundance of Escherichia-Shigella in the gut of pregnant mothers.

[0017] [3]. According to the use described in [1], the method of helping to regulate the gut microbiota of a lactating mother includes at least one of the following: increasing the relative abundance of Lactobacillus HT002 in the gut of a lactating mother, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of a lactating mother, increasing the relative abundance of Ligilactobacillus in the gut of a lactating mother, decreasing the relative abundance of Escherichia-Shigella in the gut of a lactating mother, and decreasing the relative abundance of Desulfovibrio in the gut of a lactating mother.

[0018] [4]. According to the use described in [1], wherein the method of helping to regulate the gut microbiota of offspring further includes at least one of reducing the relative abundance of Escherichia-Shigella in the offspring gut and reducing the relative abundance of Desulfovibrio in the offspring gut.

[0019] [5]. The use according to any one of [1] to [4], wherein the food is infant food, children's food, adolescent food or adult food; the adult food includes any one or more of pregnant women's food, postpartum food, pregnant and postpartum food and middle-aged and elderly food.

[0020] [6]. Use according to any one of [1] to [5], wherein the food is a confectionery, beverage, dairy product, baked food, food for special dietary use or dietary supplement.

[0021] [7]. According to the use described in [6], wherein the candy includes any one or more of hard candy, gel candy, shortbread candy, compressed candy and aerated candy; the beverage includes any one or more of carbonated beverages, tea beverages, coffee beverages, fruit and vegetable juice beverages and lactic acid bacteria beverages; the dairy product includes any one or more of fermented milk, cheese and milk powder; the baked food includes any one or more of bread, cake and biscuit; the special dietary food includes any one or more of infant formula, infant supplementary food and special medical purpose formula food; the dietary supplement includes any one or more of hard capsules, soft capsules, tablets, oral liquids, granules and powders.

[0022] [8]. The use according to any one of [1] to [7], wherein, at room temperature, the food is in liquid form, solid block form or solid powder form.

[0023] [9]. The use according to any one of [1] to [8], wherein the food contains any one or more of the following ingredients: plant product ingredients, animal dairy product ingredients, animal meat product ingredients, functional additives and any acceptable excipients in the food.

[0024]

[0010] . According to any one of [1] to [9], wherein, in the food, the mass content of 2'-fucosylated lactose is at least 0.1% relative to the total mass of the food.

[0025] The effects of the invention

[0026] Based on extensive research, this invention proposes that supplementing mothers with a certain amount of 2'-fucosylated lactose during pregnancy and / or lactation can significantly increase the abundance of beneficial bacteria and reduce the content of harmful bacteria in their intestines. At the same time, it can significantly increase the abundance of beneficial bacteria and reduce the content of harmful bacteria in the intestines of their offspring. In particular, it can regulate the abundance of some non-edible beneficial bacteria in the intestines of both mothers and offspring.

[0027] Experimental data showed that maternal supplementation with 2'-fucosylated lactose during pregnancy and lactation significantly increased the relative abundance of Akkermansia, Clostridia_UCG-014_unclassified, and Ligilactobacillus in the maternal gut during pregnancy, while decreasing the relative abundance of Escherichia-Shigella in the maternal gut during pregnancy; and increased the abundance of Lactobacillus HT002, Clostridia_UCG-014_unclassified, and Ligilactobacillus in the maternal gut during lactation. It reduced the relative abundance of *Escherichia-Shigella* and *Desulfovibrio* in the maternal gut during lactation; at the same time, it significantly increased the relative abundance of *Lactobacillus* HT002, *Akkermansia*, *Clostridia_UCG-014_unclassified*, and *Bacteroides* in the gut of breastfed offspring, and decreased the relative abundance of *Escherichia-Shigella* and *Desulfovibrio* in the gut of breastfed offspring. Attached Figure Description

[0028] Figure 1: Results of Akkermansia detection in the intestines of female mice.

[0029] Figure 2: Detection results of Clostridia_UCG-014_unclassified in the intestines of female mice.

[0030] Figure 3: Results of Ligilactobacillus detection in the intestines of female mice.

[0031] Figure 4: Detection results of Lactobacillus HT002 in the intestines of female mice.

[0032] Figure 5: Results of Bacteroides detection in the intestines of female mice.

[0033] Figure 6: Detection results of Bifidobacterium in the intestines of female mice.

[0034] Figure 7: Results of Escherichia-Shigella detection in the intestines of female mice.

[0035] Figure 8: Detection results of Desulfovibrio in the intestines of female mice.

[0036] Figure 9: Results of Akkermansia detection in the intestines of baby mice.

[0037] Figure 10: Detection results of Clostridia_UCG-014_unclassified in the intestines of baby mice.

[0038] Figure 11: Results of Ligilactobacillus detection in the intestines of baby mice.

[0039] Figure 12: Detection results of Lactobacillus HT002 in the intestines of baby mice.

[0040] Figure 13: Detection results of Bacteroides in the intestines of baby mice.

[0041] Figure 14: Detection results of Bifidobacterium in the intestines of baby mice.

[0042] Figure 15: Results of Escherichia-Shigella detection in the intestines of baby mice.

[0043] Figure 16: Detection results of Desulfovibrio in the intestines of baby mice. Detailed Implementation

[0044] The following describes embodiments of the present invention, but the present invention is not limited thereto. Various modifications can be made within the scope of protection claimed in the present invention, and 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.

[0045] In this invention, the terms "a", "an", or "the" may refer to "one", "one or more", "at least one", or "one or more".

[0046] In this invention, the range of values ​​represented by “value A to value B”, “value A to value B”, “value A and above”, “value A and below”, “at least value A” and “at most value A” refers to the range that includes the endpoint values ​​A and B.

[0047] In this invention, "optional" or "optionally" means that the event or situation described below may or may not occur, and the description includes both cases in which the event occurs and cases in which the event does not occur.

[0048] In this invention, the word "may" has two meanings: to perform a certain process and not to perform a certain process.

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

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

[0051] In this invention, "normal temperature" refers to an indoor ambient temperature of 23±2℃.

[0052] In this invention, the term "animal milk" is used to refer to the fluid obtained from the mammary glands of a mammal in the process of lactation. The term "animal milk" should be interpreted broadly and encompasses both raw milk (i.e., the fluid obtained directly from the mammary glands) and standardized dairy products.

[0053] In this invention, "gestation period" and "pregnancy period" can be used interchangeably, referring to the period from fertilization to delivery.

[0054] In this invention, "breastfeeding period" refers to the period from when a mother begins breastfeeding after childbirth until she stops breastfeeding.

[0055] In this invention, "exclusively breastfed" means that the offspring consumes the vast majority (at least 90%, preferably at least 95%, more preferably at least 98%) of its nutrients and / or energy from breast milk.

[0056] In this invention, the term "primarily breastfed" means that the nutrients and / or energy ingested by the offspring are primarily (at least 50%, preferably at least 65%, more preferably at least 75%) derived from breast milk.

[0057] In this invention, "infants and toddlers" refers to the human group under 36 months of age.

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

[0059] In this invention, "infant" refers to the human group aged 13 to 36 months.

[0060] In this invention, "children" refers to the group of humans aged 3 years and younger than 12 years.

[0061] In this invention, "adolescent" refers to the group of humans aged 12 years or older and under 18 years old.

[0062] In this invention, "adult" refers to the group of humans aged 18 years or older.

[0063] In this invention, "middle-aged and elderly" refers to the human group aged 45 years and older.

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

[0065] 2'-Fucose-based lactose

[0066] The 2'-fucosyllactose (2'-FL) described in this invention is a neutral trisaccharide composed of L-fucose, D-galactose, and D-glucose units, wherein the monosaccharide L-fucose is linked to the disaccharide D-lactose via an α(1→2) bond. Its molecular formula is C2. 18 H 31 O 15 Its molecular weight is 488.439 g / mol.

[0067] The present invention does not particularly limit the source of the 2'-fucosylated lactose. For example, it can be from natural sources, synthetic sources, microbial fermentation sources, etc. Typically, it can be synthesized through steps such as glycosylation reaction between lactose acceptor and fucose donor. Alternatively, it can be synthesized using exogenously added lactose as a substrate and 5'-guanine diphosphate nucleoside-fucose disodium salt formed through the microbial metabolic pathway as a precursor, under the action of fucosyltransferase.

[0068] In some embodiments, the mass content of 2'-fucosylated lactose may be 60% or more, preferably 80% or more, more preferably 90% or more, or any other content, relative to the total mass of the products from all sources of 2'-fucosylated lactose.

[0069] Uses of 2'-fucosylated lactose

[0070] This invention unexpectedly discovered that supplementing mothers with a certain amount of 2'-fucosylated lactose during pregnancy and / or lactation can significantly increase the abundance of beneficial bacteria in their intestines and reduce the content of harmful bacteria. At the same time, it can significantly increase the abundance of beneficial bacteria and reduce the content of harmful bacteria in the intestines of offspring through mother-to-child transmission. In particular, it can regulate the abundance of some non-directly edible beneficial bacteria such as Akkermansia in the intestines of both mother and offspring.

[0071] Based on this, the present invention provides the use of 2'-fucosyl lactose in at least one of the following (i) to (iii): (i) preparing a food that helps regulate the gut microbiota of a pregnant mother when ingested by the mother during pregnancy; (ii) preparing a food that helps regulate the gut microbiota of a lactating mother when ingested by the mother during pregnancy and / or lactation; (iii) preparing a food that helps regulate the gut microbiota of offspring when ingested by the mother during pregnancy and / or lactation; exemplary, including the use of 2'-fucosyl lactose in the preparation of a food that helps regulate the gut microbiota of a pregnant mother when ingested by the mother during pregnancy. Uses in foods that regulate the gut microbiota of pregnant and lactating mothers, in the preparation of foods that help regulate the gut microbiota of pregnant and lactating mothers when ingested by pregnant and lactating mothers, in the preparation of foods that help regulate the gut microbiota of pregnant mothers and their offspring when ingested by pregnant mothers, in the preparation of foods that help regulate the gut microbiota of lactating mothers and their offspring when ingested by lactating mothers, and in the preparation of foods that help regulate the gut microbiota of pregnant and lactating mothers and their offspring when ingested by pregnant and lactating mothers, etc.

[0072] Furthermore, the present invention provides the use of 2'-fucosyllactose in the preparation of foods that, when ingested by a mother, help regulate the gut microbiota of the mother and her offspring, wherein the mother is pregnant and / or lactating. Specifically, the present invention provides the use of 2'-fucosyllactose in the preparation of foods that, when ingested by a pregnant mother, help regulate the gut microbiota of the pregnant mother and her offspring; the use of 2'-fucosyllactose in the preparation of foods that, when ingested by a pregnant mother, help regulate the gut microbiota of a lactating mother and her offspring; the use of 2'-fucosyllactose in the preparation of foods that, when ingested by a pregnant mother, help regulate the gut microbiota of both pregnant and lactating mothers and their offspring; and the use of 2'-fucosyllactose in the preparation of foods that, when ingested by a lactating mother, help regulate the gut microbiota of the pregnant mother and her offspring. Use of 2'-fucosylated lactose in foods that regulate the gut microbiota of pregnant and lactating mothers and their offspring, use of 2'-fucosylated lactose in the preparation of foods that, when ingested by pregnant and lactating mothers, help regulate the gut microbiota of pregnant and lactating mothers and their offspring, and / or use of 2'-fucosylated lactose in the preparation of foods that, when ingested by pregnant and lactating mothers, help regulate the gut microbiota of pregnant and lactating mothers and their offspring.

[0073] In some embodiments, the offspring of the present invention are in the fetal period and / or the breastfeeding period, and the offspring in the breastfeeding period can be exclusively breastfed or primarily breastfed; preferably, the offspring of the present invention are offspring in the breastfeeding period.

[0074] This invention reveals that although 2'-fucosylated lactose is ingested by the mother, its intestinal regulatory effects on mothers and offspring at different stages are not entirely the same. In some embodiments, maternal supplementation with 2'-fucosylated lactose during pregnancy and / or lactation can regulate different gut microbiota in pregnant mothers, lactating mothers, and their offspring, respectively.

[0075] In some embodiments, the method of assisting in regulating the gut microbiota of pregnant mothers includes at least one of the following: increasing the relative abundance of Akkermansia in the gut of pregnant mothers, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of pregnant mothers, increasing the relative abundance of Ligilactobacillus in the gut of pregnant mothers, and decreasing the relative abundance of Escherichia-Shigella in the gut of pregnant mothers.

[0076] In some specific implementations, the method of helping to regulate the gut microbiota of pregnant mothers includes: increasing the relative abundance of Akkermansia in the gut of pregnant mothers and increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of pregnant mothers.

[0077] In some specific implementations, the method of helping to regulate the gut microbiota of pregnant mothers includes: increasing the relative abundance of Akkermansia and the relative abundance of Ligilactobacillus in the gut of pregnant mothers.

[0078] In some specific implementations, the method of helping to regulate the gut microbiota of pregnant mothers includes: increasing the relative abundance of Akkermansia in the gut of pregnant mothers and decreasing the relative abundance of Escherichia-Shigella in the gut of pregnant mothers.

[0079] In some specific implementations, the method of helping to regulate the gut microbiota of pregnant mothers includes: increasing the relative abundance of the unclassified genus Clostridia (UCG-014) and the relative abundance of the genus Ligilactobacillus in the gut of pregnant mothers.

[0080] In some specific implementations, the method of helping to regulate the gut microbiota of pregnant mothers includes: increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of pregnant mothers and decreasing the relative abundance of Escherichia-Shigella in the gut of pregnant mothers.

[0081] In some specific implementations, the method of helping to regulate the gut microbiota of pregnant mothers includes: increasing the relative abundance of *Ligilactobacillus* in the gut of pregnant mothers and decreasing the relative abundance of *Escherichia-Shigella* in the gut of pregnant mothers.

[0082] In some specific implementations, the method of helping to regulate the gut microbiota of pregnant mothers includes: increasing the relative abundance of Akkermansia in the gut of pregnant mothers, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of pregnant mothers, and increasing the relative abundance of Ligilactobacillus in the gut of pregnant mothers.

[0083] In some specific implementations, the method of helping to regulate the gut microbiota of pregnant mothers includes: increasing the relative abundance of Akkermansia in the gut of pregnant mothers, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of pregnant mothers, and decreasing the relative abundance of Escherichia-Shigella in the gut of pregnant mothers.

[0084] In some specific implementations, the method of helping to regulate the gut microbiota of pregnant mothers includes: increasing the relative abundance of Akkermansia in the gut of pregnant mothers, increasing the relative abundance of Ligilactobacillus in the gut of pregnant mothers, and decreasing the relative abundance of Escherichia-Shigella in the gut of pregnant mothers.

[0085] In some specific implementations, the method of helping to regulate the gut microbiota of pregnant mothers includes: increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of pregnant mothers, increasing the relative abundance of Ligilactobacillus in the gut of pregnant mothers, and decreasing the relative abundance of Escherichia-Shigella in the gut of pregnant mothers.

[0086] In some specific implementations, the method of helping to regulate the gut microbiota of pregnant mothers includes: increasing the relative abundance of Akkermansia in the gut of pregnant mothers, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of pregnant mothers, increasing the relative abundance of Ligilactobacillus in the gut of pregnant mothers, and decreasing the relative abundance of Escherichia-Shigella in the gut of pregnant mothers.

[0087] In some embodiments, the method of assisting in regulating the gut microbiota of lactating mothers includes at least one of the following: increasing the relative abundance of Lactobacillus HT002 in the lactating mother's gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the lactating mother's gut, increasing the relative abundance of Ligilactobacillus in the lactating mother's gut, decreasing the relative abundance of Escherichia-Shigella in the lactating mother's gut, and decreasing the relative abundance of Desulfovibrio in the lactating mother's gut.

[0088] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Lactobacillus HT002 and the relative abundance of Clostridia_UCG-014_unclassified in the gut of lactating mothers.

[0089] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Lactobacillus HT002 and the relative abundance of Ligilactobacillus in the gut of lactating mothers.

[0090] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Lactobacillus HT002 in the gut of lactating mothers and decreasing the relative abundance of Escherichia-Shigella in the gut of lactating mothers.

[0091] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Lactobacillus HT002 in the gut of lactating mothers and decreasing the relative abundance of Desulfovibrio in the gut of lactating mothers.

[0092] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of the unclassified genus Clostridia (UCG-014) and the relative abundance of the genus Ligilactobacillus in the gut of lactating mothers.

[0093] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of lactating mothers and decreasing the relative abundance of Escherichia-Shigella in the gut of lactating mothers.

[0094] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of lactating mothers and decreasing the relative abundance of Desulfovibrio in the gut of lactating mothers.

[0095] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of *Ligilactobacillus* and decreasing the relative abundance of *Escherichia-Shigella* in the gut of lactating mothers.

[0096] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of *Ligilactobacillus* in the gut of lactating mothers and decreasing the relative abundance of *Desulfovibrio* in the gut of lactating mothers.

[0097] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: reducing the relative abundance of Escherichia-Shigella and the relative abundance of Desulfovibrio in the gut of lactating mothers.

[0098] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Lactobacillus HT002 in the gut of lactating mothers, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of lactating mothers, and increasing the relative abundance of Ligilactobacillus in the gut of lactating mothers.

[0099] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Lactobacillus HT002 in the gut of lactating mothers, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of lactating mothers, and decreasing the relative abundance of Escherichia-Shigella in the gut of lactating mothers.

[0100] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Lactobacillus HT002 in the gut of lactating mothers, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of lactating mothers, and decreasing the relative abundance of Desulfovibrio in the gut of lactating mothers.

[0101] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Lactobacillus HT002 in the gut of lactating mothers, increasing the relative abundance of Ligilactobacillus in the gut of lactating mothers, and decreasing the relative abundance of Escherichia-Shigella in the gut of lactating mothers.

[0102] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Lactobacillus HT002 in the gut of lactating mothers, increasing the relative abundance of Ligilactobacillus in the gut of lactating mothers, and decreasing the relative abundance of Desulfovibrio in the gut of lactating mothers.

[0103] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Lactobacillus HT002 in the gut of lactating mothers, decreasing the relative abundance of Escherichia-Shigella in the gut of lactating mothers, and decreasing the relative abundance of Desulfovibrio in the gut of lactating mothers.

[0104] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of lactating mothers, increasing the relative abundance of Ligilactobacillus in the gut of lactating mothers, and decreasing the relative abundance of Escherichia-Shigella in the gut of lactating mothers.

[0105] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of lactating mothers, increasing the relative abundance of Ligilactobacillus in the gut of lactating mothers, and decreasing the relative abundance of Desulfovibrio in the gut of lactating mothers.

[0106] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of *Ligilactobacillus* in the gut of lactating mothers, decreasing the relative abundance of *Escherichia-Shigella* in the gut of lactating mothers, and decreasing the relative abundance of *Desulfovibrio* in the gut of lactating mothers.

[0107] In some specific implementations, the method of helping to regulate the gut microbiota of lactating mothers includes: increasing the relative abundance of Lactobacillus HT002 in the gut of lactating mothers, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of lactating mothers, increasing the relative abundance of Ligilactobacillus in the gut of lactating mothers, decreasing the relative abundance of Escherichia-Shigella in the gut of lactating mothers, and decreasing the relative abundance of Desulfovibrio in the gut of lactating mothers.

[0108] In some embodiments, the method of helping to regulate the gut microbiota of offspring includes at least one of: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, and increasing the relative abundance of Bacteroides in the offspring gut.

[0109] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 and Akkermansia in the offspring gut.

[0110] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut and increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut.

[0111] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 and increasing the relative abundance of Bacteroides in the offspring gut.

[0112] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia in the offspring gut and increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut.

[0113] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia and Bacteroides in the offspring gut.

[0114] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut and increasing the relative abundance of Bacteroides in the offspring gut.

[0115] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, and increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut.

[0116] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, and increasing the relative abundance of Bacteroides in the offspring gut.

[0117] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, and increasing the relative abundance of Bacteroides in the offspring gut.

[0118] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, and increasing the relative abundance of Bacteroides in the offspring gut.

[0119] In some embodiments, the method of helping to regulate the gut microbiota of offspring further includes at least one of reducing the relative abundance of Escherichia-Shigella and reducing the relative abundance of Desulfovibrio in the offspring gut.

[0120] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring gut.

[0121] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring gut.

[0122] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring gut.

[0123] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring gut.

[0124] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring gut.

[0125] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring gut.

[0126] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring gut.

[0127] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring gut.

[0128] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring gut.

[0129] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Escherichia-Shigella in the offspring gut.

[0130] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0131] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0132] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0133] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0134] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0135] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0136] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0137] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0138] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0139] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0140] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, decreasing the relative abundance of Escherichia-Shigella in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0141] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, decreasing the relative abundance of Escherichia-Shigella in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0142] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, decreasing the relative abundance of Escherichia-Shigella in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0143] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, decreasing the relative abundance of Escherichia-Shigella in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0144] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, decreasing the relative abundance of Escherichia-Shigella in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0145] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, decreasing the relative abundance of Escherichia-Shigella in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0146] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, decreasing the relative abundance of Escherichia-Shigella in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0147] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, decreasing the relative abundance of Escherichia-Shigella in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0148] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, decreasing the relative abundance of Escherichia-Shigella in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0149] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, decreasing the relative abundance of Escherichia-Shigella in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0150] In some specific implementations, the method of helping to regulate the gut microbiota of offspring includes: increasing the relative abundance of Lactobacillus HT002 in the offspring gut, increasing the relative abundance of Akkermansia in the offspring gut, increasing the relative abundance of Clostridia_UCG-014_unclassified in the offspring gut, increasing the relative abundance of Bacteroides in the offspring gut, decreasing the relative abundance of Escherichia-Shigella in the offspring gut, and decreasing the relative abundance of Desulfovibrio in the offspring gut.

[0151] Through extensive research, this invention has found that supplementing mothers with 2'-fucosylated lactose during pregnancy and / or lactation can simultaneously regulate some of the same gut microbiota in pregnant mothers, lactating mothers, and their offspring.

[0152] In some specific implementations, the method of helping to regulate the gut microbiota of mothers and their offspring includes simultaneously increasing the relative abundance of the unclassified genus Clostridia (UCG-014) in the gut of pregnant mothers, lactating mothers, and their offspring.

[0153] In some specific implementations, the method of helping to regulate the gut microbiota of mothers and their offspring includes simultaneously reducing the relative abundance of Escherichia-Shigella in the gut of pregnant mothers, lactating mothers, and their offspring.

[0154] In some specific implementations, the method of helping to regulate the gut microbiota of mothers and their offspring includes simultaneously increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of pregnant mothers, lactating mothers and their offspring, and simultaneously decreasing the relative abundance of Escherichia-Shigella in the gut of pregnant mothers, lactating mothers and their offspring.

[0155] Furthermore, this study found that supplementing the mother's diet with 2'-fucosylated lactose during pregnancy can simultaneously increase the relative abundance of Akkermansia in the intestines of both the mother and her offspring. Previous studies have found 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, thereby playing 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 plays an important role in a variety of neuropsychiatric disorders, such as depression and anxiety, autism spectrum disorders (ASDs), Alzheimer's disease, and cognitive impairment, and has the potential to serve as a therapeutic target for various neuropsychiatric disorders. Similarly, studies have shown that the number of Bacteroides in the feces of children with autism is reduced, while the level of Desulfovibrio is increased (Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, Soleimanpour SA 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.). The present invention found that when mothers supplement their diet with 2'-fucosylated lactose during pregnancy, it can increase the relative abundance of Bacteroides in the intestines of their offspring and decrease the relative abundance of Desulfovibrio in the intestines of their offspring.

[0156] Therefore, this invention suggests that supplementing mothers with 2'-fucosylated lactose during pregnancy and / or lactation is not only beneficial to the health of the gut microbiota of the mother and her offspring, but also beneficial to the gut-brain axis function of the mother and her offspring, thereby playing a certain beneficial role in the health of the nervous system of the mother and her offspring.

[0157] In some embodiments, the regulation of the gut microbiota of pregnant mothers, the regulation of the gut microbiota of lactating mothers, and the regulation of the gut microbiota of offspring described in this invention are not for the purpose of treating or preventing diseases.

[0158] This invention does not specifically limit the types of foods that, when ingested by pregnant and / or lactating mothers, help regulate the gut microbiota of pregnant and / or lactating mothers and their offspring.

[0159] In some embodiments, the food described in this invention can be infant food, children's food, adolescent food, or adult food; the adult food includes any one or more of the following: food for pregnant women, food for postpartum women, food for pregnant and postpartum women, and food for middle-aged and elderly people.

[0160] In some embodiments, the food products described in this invention are candies, beverages, dairy products, baked goods, or dietary supplements. For example, the candies include hard candies, gel candies, shortbread candies, compressed candies, and aerated candies; the beverages include carbonated beverages, tea beverages, coffee beverages, fruit and vegetable juice beverages, and lactic acid bacteria beverages; the dairy products include fermented milk, cheese, and milk powder; the baked goods include bread, cakes, and biscuits; and the dietary supplements include hard capsules, soft capsules, tablets, oral liquids, granules, and powders.

[0161] In some embodiments, the food described in this invention is a special dietary food; the special dietary food includes infant formula, infant complementary food, supplementary nutritional products, and special medical purpose formula food, etc.

[0162] In some embodiments, at room temperature, the food described in this invention is in liquid form, solid block form, or solid powder form. For example, the liquid form includes oral liquids, lactic acid bacteria beverages, and formulated liquid milk; the solid block form includes hard candies, biscuits, cheese, and dietary supplement tablets; and the solid powder form includes reconstituteable beverages.

[0163] In some specific implementations, the food described in this invention is a formula milk powder for pregnant and postpartum women or a dietary supplement for pregnant and postpartum women, such as oral liquid for pregnant and postpartum women.

[0164] In some embodiments, the food described in this invention is an artificially prepared food, that is, not a natural food such as animal milk.

[0165] This invention does not specifically limit the absolute content of 2'-fucosyllactose in food, as long as it meets the requirements of local food-related laws and regulations. In some embodiments, the mass content of 2'-fucosyllactose relative to the total mass of the food is at least 0.05%, preferably at least 0.1%, more preferably at least 1%, and even more preferably at most 12%.

[0166] In addition to 2'-fucosylated lactose, the food products described in this invention may also contain other ingredients, such as proteins / amino acids, carbohydrates, fats, vitamins, minerals, and other components commonly found in food.

[0167] Furthermore, depending on the type of food and the end needs of the target audience, in some embodiments, 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.

[0168] Examples of plant-based ingredients include fruits such as figs, pomegranates, kiwis, oranges, tangerines, pineapples, strawberries, apples, bananas, grapes, pears, cherries, blueberries, blackberries, blackcurrants, cranberries, raspberries, melons, amla, and bilberries, or their extracts; fruits and vegetables such as onions, cucumbers, tomatoes, cauliflower, carrots, spinach, kale, Brussels sprouts, garlic, basil, and oregano, or their extracts; grains such as rice (indica, japonica, glutinous rice), cereals (wheat, barley, oats, rye), corn, sorghum, millet, sorghum, yellow millet, buckwheat, soybeans, broad beans, peas, mung beans, red beans, and kidney beans, or their extracts; nuts such as walnuts, pistachios, cashews, hazelnuts, almonds, apricot kernels, pine nuts, peanuts, sunflower seeds, chestnuts, macadamia nuts, and ginkgo nuts, or their extracts; coffee or its extracts; and some medicinal and edible herbal medicines or their extracts.

[0169] Animal dairy product ingredients can include fresh milk from cows and sheep, as well as reprocessed dairy products such as whole milk powder, skim milk powder, whey protein concentrate, desalted whey powder, whey protein powder, hydrolyzed whey protein powder, and casein powder.

[0170] Examples of animal meat product ingredients include pork, beef, mutton, seafood, and poultry.

[0171] Examples of functional additives include vitamin supplements, mineral supplements, nucleotide supplements, dietary fiber, and functional polyunsaturated fatty acid supplements.

[0172] 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 pigments, etc.

[0173] Examples

[0174] The embodiments of the present invention will be described in detail below in combination with examples. However, those skilled in the art will understand that the following examples are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. For those not specified in the examples, the conventional conditions or the conditions recommended by the manufacturer are followed. Unless otherwise specified, the materials or instruments used are conventional products that can be obtained through commercial purchase.

[0175] 1. Detection materials

[0176] 1.1. Experimental animals and grouping

[0177] Forty 8-week-old sexually mature SPF-grade female rats and forty SPF-grade male rats were selected; they were purchased from Hangzhou Medical College, with the animal certificate number being 20240318Aazz0100000836 and the production license number: SCXK(Zhe)2024-002. Feeding conditions: The animals were raised in a barrier environment, with the indoor temperature at 25±1°C and the humidity at 45±5%. The animals had free access to drinking water in the facility and were raised in a 12h light-dark cycle environment daily. This experiment passed the animal experiment ethical review of Southeast University, with the ethics number: 20240316003.

[0178] After 3 days of adaptive feeding of the animals, the female and male rats were caged together at a ratio of 1:1. Taking the appearance of a vaginal plug in the female rat as the starting point for gavage intervention, continuous gavage was performed on the female rat until after the offspring rats were weaned; in the experimental group, the corresponding dose of the sample aqueous solution was given according to the animal grouping, and in the control group, the corresponding dose of normal saline was given. Gavage was performed once a day for 6 consecutive weeks, and a maintenance diet was given to each dose group. Among them, the low and high doses of 2'-fucosyllactose in the intervention group were 12.6 and 37.8 (mg / d / rat). The specific doses of each group are shown in Table 1 below. The feces of the female rats before gavage, after parturition, and after weaning, as well as the feces of the offspring rats at one week and three weeks (after weaning) were collected respectively for intestinal flora sequencing.

[0179] Table 1 Gavage doses of experimental animals

[0180] 1.2. Instruments, consumables and reagents

[0181] The consumables, reagents and experimental instruments used in the experiment are shown in Tables 2 and 3.

[0182] Table 2 Main experimental consumables and reagents

[0183] Table 3 Main Experimental Instruments

[0184] 2. Detection Method

[0185] 2.1. Collection of feces from mother and offspring

[0186] (1) Collection of feces from female mice: Fresh feces from each female mouse were collected in a clean environment before gavage, after parturition, and after weaning. The feces were numbered and stored at -80℃.

[0187] (2) Collection of feces from pups: Fresh feces from each litter of pups were collected at 1 week and 3 weeks after birth (after weaning), numbered, and then frozen at -80℃.

[0188] 2.2. Detection of fecal microbiota in female and offspring mice

[0189] High-throughput sequencing of microorganisms in fecal samples from mother and offspring mice was performed using 16S rDNA.

[0190] (1) Total microbiome DNA extraction: Total microbiome DNA was extracted from feces using a DNA extraction kit, and the quality of DNA extraction was detected by agarose gel electrophoresis. At the same time, the DNA was quantified using a UV spectrophotometer.

[0191] (2) PCR amplification: The V3-V4 region of bacterial 16S rDNA was selected for gene amplification and sequencing. Primer sequences are shown in Table 4 below:

[0192] Table 4 Primer sequences

[0193] The PCR reaction system is shown in Table 5 below:

[0194] Table 5 Reaction System

[0195] The PCR reaction conditions are shown in Table 6 below:

[0196] Table 6 Reaction conditions

[0197] (3) The PCR products were purified by AMPure XT beads (Beckman Coulter Genomice, MA, USA) and quantified by Qubit (Invitrogen, USA).

[0198] (4) The purified PCR products were evaluated using an Agilent 2100 bioanalyzer (Agilent, USA) and Illumina (Kapa Biosciences, Wobum, MA, USA) library quantification kit. Qualified libraries had a concentration above 2 nM. Each qualified sequencing library was serially diluted and mixed according to the required sequencing volume, then denatured into single strands using NaOH before sequencing. 2×250 bp paired-end sequencing was performed using a NovaSeq 6000 sequencer, with the corresponding reagent being the NovaSeq 6000SP Reagent Kit (500 cycles).

[0199] (5) For the paired-end data obtained from sequencing, the samples were first split according to the barcode information, and adapters and barcode sequences were removed. Then, the sequences were assembled to obtain optimized sequences. After removing chimeric sequences, OUT cluster analysis was performed, and taxonomic analysis was conducted on the representative OUT sequences. Based on the OUT cluster analysis results, various diversity index analyses and sequence depth detection were performed on the OUT sequences; based on taxonomic information, statistical analysis of colony structure was performed at each taxonomic level.

[0200] 3. Test Results

[0201] 3.1 Results of dominant gut microbiota in female mice

[0202] 3.1.1. Changes in Akkermansia in the intestines of female mice

[0203] Akkermansia is a genus of Gram-negative anaerobic bacteria in the gut, primarily colonizing the mucus layer of the gastrointestinal tract and protecting it and connective tissue. As a new generation of probiotics, it serves as a biomarker of health. Studies have shown that Akkermansia plays an important probiotic role in metabolic diseases (diabetes, obesity, etc.), intestinal diseases (inflammatory bowel disease, ulcerative colitis, etc.), and neuropsychiatric conditions.

[0204] As shown in Figure 1, compared with the control group, 2'-fucosyllactose can increase the relative abundance of Akkermansia in the gut during pregnancy, and the high-dose intervention group (Example 2) shows a significantly higher increase than the low-dose intervention group (Example 1). The abundance of Akkermansia in the gut of lactating mothers after weaning is lower than its relative abundance after delivery, and the relative abundance of 2'-fucosyllactose in different dose intervention groups is higher than that in the control group.

[0205] 3.1.2. Changes in the Clostridia genus (UCG-014_unclassified) in the intestines of female mice

[0206] *Clostridia* (UCG-014 unclassified) is an unnamed genus within the class Clostridium. It comprises a group of Gram-positive anaerobic or microaerophilic bacteria, with a large number of butyric acid-producing bacteria belonging to this genus. Studies have found that the relative abundance of *Clostridia* (UCG-014 unclassified) in the gut of patients with thyroiditis is decreased compared to healthy individuals. Some studies have also found a negative correlation between the relative abundance of *Clostridia* (UCG-014 unclassified) in the gut during pregnancy and dyslipidemia during pregnancy.

[0207] As shown in Figure 2, compared with the control group, 2'-fucosylated lactose can increase the relative abundance of Clostridia_UCG-014_unclassified in the gut during pregnancy, and the increase in the high-dose intervention group (Example 2) is significantly higher than that in the low-dose intervention group (Example 1). The abundance of Clostridia_UCG-014_unclassified in the gut of lactating mothers after weaning is lower than that after delivery, and the relative abundance in the high-dose intervention group (Example 2) of 2'-fucosylated lactose is higher than that in other dose groups.

[0208] 3.1.3. Changes in *Ligilactobacillus* spp. in the intestines of female mice

[0209] *Ligilactobacillus* is a genus of Gram-positive bacteria widely found in nature, primarily in the animal digestive system, oral cavity, intestines, and vagina. *Ligilactobacillus* can digest and utilize proteins and carbohydrates, synthesize B vitamins and vitamin K in the intestines, break down and metabolize bile salts, and enhance the body's innate and acquired immunity. Furthermore, strains of *Ligilactobacillus* can ferment to produce short-chain fatty acids (SCFAs), which inhibit the proliferation of harmful bacteria in the intestines and promote the growth of beneficial bacteria.

[0210] As shown in Figure 3, compared with the control group, the different intervention doses of 2'-fucosylated lactose in Examples 1 and 2 could increase the relative abundance of Ligilactobacillus in the intestines of pregnant mice; after weaning, the relative abundance of Ligilactobacillus in the intestines of pregnant mice in Examples 1 and 2 with different intervention doses of 2'-fucosylated lactose was significantly higher than that in the control group.

[0211] 3.1.4. Changes in Lactobacillus HT002 in the intestines of female mice

[0212] Lactobacillus HT002 is a genus within the family Lactobacillusceae. It is a Gram-positive facultative anaerobic bacterium that ferments carbohydrates to produce lactic acid and other short-chain fatty acids, making it a type of probiotic. Studies have shown that Lactobacillus HT002 in the gut is closely related to lipid metabolism in the body.

[0213] As shown in Figure 4, compared with the control group, from the beginning of pregnancy to after parturition, the relative abundance of Lactobacillus HT002 in the intestines of female mice in Examples 1 and 2 was significantly lower than that in the control group, and there was no significant difference among different intervention dose groups; after weaning, the relative abundance of Lactobacillus HT002 in the intestines of female mice in Examples 1 and 2 in different intervention dose groups of 2'-fucosylated lactose was significantly higher than that in the control group.

[0214] 3.1.5. Changes in Bacteroides in the gut of female mice

[0215] Bacteroides are primarily found in the intestines, oral cavity, upper respiratory tract, and reproductive tract of humans and animals, with the intestines being the most abundant. They are Gram-negative, non-spore-forming obligate anaerobic bacteria. Bacteroides can break down and metabolize various carbohydrates and digest various dietary fibers, producing short-chain fatty acids to maintain the balance of the intestinal flora. Furthermore, Bacteroides can regulate the body's immune system through their capsular polysaccharides. Studies have found a negative correlation between the abundance of Bacteroides in the gut during pregnancy and dyslipidemia during pregnancy.

[0216] As shown in Figure 5, compared with the control group, the relative abundance of Bacteroides in the intestines of pregnant mice in different intervention dose groups of 2'-fucosylated lactose in Examples 1 and 2 showed a decreasing trend, and the relative abundance was lower than that in the control group; indicating that different intervention doses of 2'-fucosylated lactose had no proliferative effect on Bacteroides in the intestines of pregnant mice.

[0217] 3.1.6. Changes in Bifidobacterium in the gut of female mice

[0218] Bifidobacterium is a Gram-positive, non-acid-resistant, non-motile obligate anaerobic bacterium isolated from the feces of breastfed infants. It is widely distributed in the intestines of humans and animals, as well as the rumen of ruminants. Small amounts of Bifidobacterium are also found in the vagina, oral cavity, and breast milk in humans. Bifidobacterium is currently recognized as a probiotic with various beneficial functions, such as improving intestinal diseases caused by immune system disorders, such as inflammatory bowel disease and ulcerative colitis; improving diseases caused by dysbiosis, such as constipation and diarrhea; breaking down lactose to alleviate lactose intolerance; inhibiting the growth and reproduction of putrefactive bacteria; and enhancing the body's immunity.

[0219] As shown in Figure 6, compared with the control group, there was no significant change in the relative abundance of Bifidobacterium in the intestines of female mice in Examples 1 and 2 with different intervention doses of 2'-fucosylated lactose from the beginning of pregnancy to delivery and after weaning.

[0220] 3.1.7. Changes in Escherichia-Shigella in the gut of female mice

[0221] Escherichia-Shigella is a genus of Enterobacteriaceae. It is a common pathogenic bacterium in the intestines, a Gram-negative facultative anaerobic bacterium. It has low nutritional requirements for growth and can produce enterotoxins that are highly pathogenic. Its proliferation can cause intestinal flora imbalance and lead to bacterial dysentery.

[0222] As shown in Figure 7, compared with the control group, the relative abundance of Escherichia-Shigella in the intestines of female mice in Examples 1 and 2 after parturition and weaning in different doses of 2'-fucosylated lactose intervention groups was lower than that in the control group, indicating that different intervention groups of 2'-fucosylated lactose can inhibit the proliferation of pathogenic bacteria in the intestine to a certain extent.

[0223] 3.1.8. Changes in Desulfovibrio in the intestines of female mice

[0224] Desulfovibrio, also known as sulfate-reducing bacteria, is a Gram-negative, non-fermenting anaerobic bacterium that produces hydrogen sulfide through metabolism and is a common pathogen. It is widely found in soil, water, sewage, and the digestive tracts of animals and humans. Excessive proliferation in the intestines can be toxic to the intestinal epithelium, leading to gastrointestinal diseases.

[0225] As shown in Figure 8, compared with the control group, there was no significant difference in the relative abundance of Desulfovibrio in the intestines of mother mice in different doses of 2'-fucosylated lactose in Examples 1 and 2 after parturition; however, after weaning, the relative abundance of Desulfovibrio in the intestines of mother mice in different doses of 2'-fucosylated lactose in Examples 1 and 2 was significantly lower than that in the control group.

[0226] 3.2. Results of dominant gut microbiota in offspring mice

[0227] 3.2.1. Changes in Akkermansia in the intestines of offspring mice

[0228] As shown in Figure 9, there was no significant difference in the relative abundance of Akkermansia in the intestines of offspring mice in different dosage groups one week after birth. However, with continued breastfeeding, the relative abundance of Akkermansia in the intestines of offspring mice in Examples 1 and 2, which involved different doses of 2'-fucosylated lactose, was significantly higher than that in the control group. This indicates that administering 2'-fucosylated lactose to the mother from the start of pregnancy until the end of breastfeeding can significantly increase the relative abundance of Akkermansia in the offspring intestines.

[0229] 3.2.2. Changes in the Clostridia genus (UCG-014_unclassified) in the intestines of offspring mice

[0230] As shown in Figure 10, there was no significant difference in the relative abundance of Clostridia_UCG-014_unclassified in the intestines of offspring mice in different dose groups one week after birth. With the continuation of breastfeeding, the relative abundance of Clostridia_UCG-014_unclassified in the intestines of offspring mice in the low-dose intervention group (Example 1) was higher than that in the control group, while there was no significant difference between the high-dose intervention group (Example 2) and the control group.

[0231] 3.2.3. Changes in *Ligilactobacillus* spp. in the intestines of offspring mice

[0232] As shown in Figure 11, one week after birth, the relative abundance of *Ligilactobacillus* in the intestines of mice in different intervention dose groups of 2'-fucosylated lactose (Examples 1 and 2) was higher than that in the control group. Furthermore, the relative abundance of *Ligilactobacillus* in the intestines of mice in the high-dose intervention group (Example 2) was significantly higher than that in the control group. With continued breastfeeding, the relative abundance of *Ligilactobacillus* in the intestines of mice in different intervention dose groups of 2'-fucosylated lactose did not differ significantly from that at one week after birth, and was lower than that in the control group.

[0233] 3.2.4. Changes in Lactobacillus HT002 in the intestines of offspring mice

[0234] As shown in Figure 12, compared with the control group, there was no significant increase in the relative abundance of *Lactobacillus HT002* in the intestines of offspring mice one week after birth. With prolonged breastfeeding until weaning, the relative abundance of *Lactobacillus HT002* in the intestines of offspring mice in different doses of 2'-fucosylated lactose intervention groups (Examples 1 and 2) was significantly higher than that in the control group. Furthermore, the relative abundance of *Lactobacillus HT002* in the intestines of offspring mice in the high-dose group (Example 2) was higher than that in the low-dose group (Example 1). This indicates that administering 2'-fucosylated lactose to the mother from the start of pregnancy until the end of breastfeeding can significantly increase the relative abundance of *Lactobacillus HT002* in the offspring intestines.

[0235] 3.2.5. Changes in Bacteroides in the intestines of offspring mice

[0236] As shown in Figure 13, compared with the control group, there was no significant change in the relative abundance of Bacteroides in the intestines of offspring mice in different intervention dose groups of 2'-fucosylated lactose one week after birth; as breastfeeding continued until weaning, the relative abundance of Bacteroides in the intestines of offspring mice in the low-dose intervention group of Example 1 was significantly higher than that in the control group.

[0237] 3.2.6. Changes in Bifidobacterium in the intestines of offspring mice

[0238] As shown in Figure 14, compared with the control group, there was no significant change in the relative abundance of Bifidobacterium in the intestines of mice in different intervention dose groups of fucosylated lactose from 1 week after birth to 2'-2 weeks after weaning.

[0239] 3.2.7. Changes in Escherichia-Shigella in the intestines of offspring mice

[0240] As shown in Figure 15, compared with the control group, from one week after birth to after weaning, the relative abundance of *Escherichia-Shigella* in the intestines of offspring mice in different doses of 2'-fucosylated lactose intervention groups (Examples 1 and 2) was lower than that in the control group, and the relative abundance in the high-dose intervention group (Example 2) was lower than that in the low-dose intervention group (Example 1). This indicates that administering 2'-fucosylated lactose to the mother from the beginning of pregnancy until the end of breastfeeding can significantly inhibit the relative abundance of harmful *Escherichia-Shigella* in the offspring intestines.

[0241] 3.2.8. Changes in Desulfovibrio in the intestines of offspring mice

[0242] As shown in Figure 16, compared with the control group, the relative abundance of *Desulfovibrio* in the intestines of offspring mice in the different doses of 2'-fucosylated lactose intervention groups (Examples 1 and 2) was lower one week after birth, and the content of *Desulfovibrio* in the different dose groups did not differ significantly. With the continuation of breastfeeding, the relative abundance of *Desulfovibrio* in the intestines of offspring mice in the different doses of 2'-fucosylated lactose intervention groups (Examples 1 and 2) was significantly lower than that in the control group after weaning. This indicates that administering 2'-fucosylated lactose to the mother from the beginning of pregnancy until the end of breastfeeding can significantly inhibit the proliferation of harmful bacteria *Desulfovibrio* in the offspring intestines and reduce its relative abundance in the intestines.

Claims

1. Use of human milk oligosaccharide in the preparation of food that helps regulate the gut microbiota of mother and offspring when ingested by the mother, wherein the human milk oligosaccharide is 2'-fucosylated lactose, and the mother is pregnant and / or lactating; The gut microbiota that helps regulate offspring includes: Increase the relative abundance of Lactobacillus HT002 in the progeny gut, increase the relative abundance of Akkermansia in the progeny gut, increase the relative abundance of Clostridia_UCG-014_unclassified in the progeny gut, and increase the relative abundance of Bacteroides in the progeny gut.

2. The use according to claim 1, characterized in that, The methods for regulating the gut microbiota of pregnant mothers include at least one of the following: increasing the relative abundance of Akkermansia in the gut of pregnant mothers, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of pregnant mothers, increasing the relative abundance of Ligilactobacillus in the gut of pregnant mothers, and decreasing the relative abundance of Escherichia-Shigella in the gut of pregnant mothers.

3. The use according to claim 1, characterized in that, The methods for regulating the gut microbiota of lactating mothers include: increasing the relative abundance of Lactobacillus HT002 in the gut of lactating mothers, increasing the relative abundance of Clostridia_UCG-014_unclassified in the gut of lactating mothers, increasing the relative abundance of Ligilactobacillus in the gut of lactating mothers, decreasing the relative abundance of Escherichia-Shigella in the gut of lactating mothers, and decreasing the relative abundance of Desulfovibrio in the gut of lactating mothers.

4. The use according to claim 1, characterized in that, The gut microbiota that helps regulate offspring also includes at least one of reducing the relative abundance of Escherichia-Shigella and reducing the relative abundance of Desulfovibrio in the offspring gut.

5. The use according to any one of claims 1 to 4, characterized in that, The food is infant food, children's food, adolescent food, or adult food; the adult food includes any one or more of the following: food for pregnant women, food for postpartum women, food for pregnant and postpartum women, and food for middle-aged and elderly people.

6. The use according to any one of claims 1 to 5, characterized in that, The food products mentioned are candies, beverages, dairy products, baked goods, special dietary foods, or dietary supplements.

7. The use according to claim 6, characterized in that, The candy includes any one or more of hard candy, gel candy, shortbread candy, compressed candy, and aerated candy; the beverage includes any one or more of carbonated beverages, tea beverages, coffee beverages, fruit and vegetable juice beverages, and lactic acid bacteria beverages; the dairy products include any one or more of fermented milk, cheese, and milk powder; the baked goods include any one or more of bread, cakes, and biscuits; the special dietary foods include any one or more of infant formula, infant complementary foods, and special medical purpose formula foods; the dietary supplements include any one or more of hard capsules, soft capsules, tablets, oral liquids, granules, and powders.

8. The use according to any one of claims 1 to 7, characterized in that, At room temperature, the food is in liquid form, solid block form, or solid powder form.

9. 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-based ingredients, animal dairy ingredients, animal meat ingredients, functional additives, and any acceptable excipients in the food.

10. The use according to any one of claims 1 to 9, characterized in that, The 2'-fucosylated lactose is present in the food at a mass content of at least 0.1%.

11. Use of human milk oligosaccharides in the preparation of foods that, when ingested by the mother, contribute to improving the neurological health of the mother and her offspring; wherein, The human milk oligosaccharide is 2'-fucosylated lactose; the mother is pregnant and / or lactating; the food helps improve the nervous system health of the mother and her offspring by regulating the gut microbiota of the mother and her offspring.

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