Nutritional composition and nutritional supplement for maintaining stability of intestinal flora diversity during pregnancy and improving newborn birth outcome

Abstract

The invention discloses a nutritional composition. The nutritional composition comprises animal protein, vegetable protein and prebiotics, in the nutritional composition, the mass ratio of the animal protein to the vegetable protein to the prebiotics is 1: (3-6): (0.4-0.8). The invention also discloses application of the nutritional composition in maintaining stable diversity of intestinal flora during pregnancy and improving the birth outcome of newborns. According to the nutritional composition provided by the invention, by optimizing the ratio of the resistant dextrin to the protein and reasonably adjusting the ratio of the plant protein to the animal protein, the alpha diversity stability of intestinal flora in each stage (including early pregnancy, middle pregnancy and late pregnancy) of pregnancy can be effectively maintained; moreover, the growth retardation of the newborns can be reduced, the premature birth rate and the low birth weight incidence rate are reduced, and the birth outcome of the newborns is remarkably improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of nutritional medicine and microbiome, and in particular to a nutritional composition for maintaining the stability of intestinal flora diversity during pregnancy and improving the birth outcomes of newborns and a nutritional supplement comprising the same. BACKGROUND

[0002] Studies have shown that the dynamic changes of intestinal flora during pregnancy are closely related to maternal and infant health and birth outcomes. Flora imbalance can lead to inflammatory reactions, metabolic abnormalities, and affect fetal development (such as Nutrition during pregnancy: Influence on the gut microbiome and fetal development, American J Rep Immunol, 2023, Barrientos, et al.), resulting in birth outcomes such as premature birth, low birth weight, and developmental delay. In the early stages of pregnancy, stable intestinal flora can protect the reproductive tract, regulate intestinal immunity, and reduce the risk of miscarriage and pregnancy complications; in the second trimester, stable intestinal flora can promote fetal immune development and maintain maternal metabolic homeostasis; in the third trimester, stable intestinal flora lays the foundation for childbirth and neonatal flora colonization, and regulates maternal mood. Overall, through the mechanism of "anti-infection-regulating metabolism-shaping immunity", it reduces premature birth, low birth weight, and neonatal infection, optimizes fetal growth and delivery mode, and also reduces the long-term health risks of offspring such as allergies and obesity through vertical transmission. Based on this, it is recommended to maintain the health of the flora through dietary adjustments, avoid the misuse of antibiotics, and lay a solid foundation for the short-term safety of mother and child and the long-term health of offspring.

[0003] In the prior art, a special nutritional pack for pregnant and lying-in women is a nutritional supplement product designed for pregnant women and lactating mothers, aiming to provide comprehensive nutrition for the mother and fetus, helping women maintain health during pregnancy, childbirth, and lactation. This type of nutritional pack usually contains vitamins, minerals, folic acid, iron, calcium, DHA, and other ingredients to help make up for nutritional deficiencies in daily diet, support fetal development, enhance maternal immunity, supplement blood, and prevent anemia and other problems. However, this type of special nutritional pack for pregnant and lying-in women lacks comprehensive design for flora diversity and cannot meet the needs of improving maternal and infant health by regulating intestinal flora. SUMMARY

[0004] The technical problem to be solved by the present application is to provide a nutritional composition for pregnant and lying-in women, which can maintain the stability of intestinal flora diversity during pregnancy and significantly improve the birth outcomes of newborns.

[0005] To solve the above technical problems, the present application provides the following technical solutions: The present application provides a nutritional composition comprising animal protein, plant protein and prebiotics; wherein the mass ratio of the animal protein, the plant protein and the prebiotics in the nutritional composition is 1:(3-6):(0.5-0.8).

[0006] Further, the animal protein can be derived from meat, aquatic products, eggs, dairy products and the like, preferably whey protein. The plant protein can be derived from legumes, nuts, cereals and the like, preferably soy protein.

[0007] Further, the prebiotics are selected from any one or combination of resistant dextrin, fructooligosaccharide, galactooligosaccharide, inulin, polydextrose, xylooligosaccharide and resistant starch, preferably resistant dextrin. Resistant dextrin is a water-soluble dietary fiber that can be fermented by the intestinal flora to provide energy substrates for beneficial bacteria (such as Bifidobacterium, Faecalibacterium, Roseburia, etc.) and promote their proliferation.

[0008] In the present application, the inventors found that the nutritional composition formed by the combination of animal protein, plant protein and prebiotics in a certain ratio can achieve the technical effect of maintaining the stability of the intestinal flora during pregnancy. Although the biological value (BV=104) of animal protein whey protein is higher than that of plant protein (soy protein BV=74), plant protein has the characteristic of slow digestion, so by optimizing the ratio of animal protein and plant protein, the release of amino acids can be prolonged. During the third trimester of pregnancy and lactation, the intake of prebiotics can specifically promote the increase of the relative abundance of Bifidobacterium and enhance the intestinal barrier function and immune regulation ability. By maintaining the stability of butyrate-producing bacteria such as Faecalibacterium and Roseburia (0.2-0.3 throughout pregnancy), the anti-inflammatory effect and the role of maintaining the intestinal barrier are exerted.

[0009] In summary, by optimizing the ratio of prebiotics and protein (animal protein and plant protein), the release of amino acids can be prolonged, and at the same time, a continuous fermentation substrate is provided for the flora, so as to maintain the stability of the flora alpha diversity in the early, middle and late stages of pregnancy, and avoid inflammation or metabolic abnormalities caused by flora imbalance. In addition, by regulating the flora metabolism, the maternal metabolic homeostasis (such as regulating blood glucose and energy balance) is maintained, the risk of pregnancy complications is reduced, and the intestinal immune regulation is promoted to reduce early pregnancy loss and late inflammatory response.

[0010] In the nutritional composition of the present application, the mass ratio of animal protein, plant protein and prebiotics can be 1:3:0.5, 1:3:0.6, 1:3:0.8, 1:5:0.5, 1:5:0.6, 1:5:0.8, 1:6:0.5, 1:6:0.6, 1:6:0.8, etc.; preferably, the mass ratio of animal protein, plant protein and prebiotics in the nutritional composition is 1:(4-6):(0.6-0.8), and further preferably 1:5:0.686.

[0011] The second aspect of the present application provides the use of the nutritional composition in the preparation of a product for maintaining the stability of the intestinal flora diversity during pregnancy.

[0012] Further, the stability of the intestinal flora diversity during pregnancy refers to the stability of the alpha diversity of the flora at each stage (early, middle and late) of pregnancy, and the relative stability of the dominant flora in different stages of pregnancy.

[0013] The third aspect of the present application provides the use of the nutritional composition in the preparation of a product for improving the birth outcome of a newborn.

[0014] Further, the birth outcome of the newborn includes at least one of (i)~(iii): (i) developmental delay; (ii) premature birth; (iii) low birth weight.

[0015] The nutritional composition provided by the present application can help maintain maternal metabolic homeostasis (such as regulating blood glucose and energy balance) by regulating flora metabolism, reduce the risk of pregnancy complications; reduce early pregnancy miscarriage and late inflammatory response by promoting intestinal immune regulation. That is, the stability of the flora diversity reduces adverse outcomes such as developmental delay, premature birth, and low birth weight through the "anti-infection-metabolism-shaping immunity" mechanism.

[0016] The fourth aspect of the present application provides a nutritional supplement for pregnant women, wherein the nutritional supplement comprises the nutritional composition; and fat, carbohydrate, sodium, vitamin A, vitamin B, vitamin C, vitamin D, folic acid, calcium, iron, zinc and DHA. The vitamin B includes vitamin B1, vitamin B2, vitamin B6 and vitamin B12.

[0017] Further, the nutritional supplement comprises 3.5~4g of the nutritional composition, 1~2g of fat, 8~9g of carbohydrate, 30~35mg of sodium, 400~600ug of vitamin A, 1~1.5mg of vitamin B1, 1~1.5mg of vitamin B2, 1~2mg of vitamin B6, 2~3ug of vitamin B12, 80~120mg of vitamin C, 6~8ug of vitamin D, 150~250ug of folic acid, 300~500mg of calcium, 10~15mg of iron, 6~9mg of zinc and 60~70mg of DHA per 15g of the nutritional supplement.

[0018] Further, in the preferred embodiment, each 15g of the nutritional supplement includes: 3.9g of the nutritional composition, 1.5g of fat, 8.5g of carbohydrate, 31mg of sodium, 500ug of vitamin A, 1.2mg of vitamin B1, 1.2mg of vitamin B2, 1.5mg of vitamin B6, 2.5ug of vitamin B12, 100mg of vitamin C, 6.5ug of vitamin D, 200ug of folic acid, 400mg of calcium, 12mg of iron, 7.5mg of zinc, and 65mg of DHA.

[0019] Further, the nutritional supplement of the present application can be prepared into various dosage forms, including but not limited to oral liquids, tablets, powders, capsules, granules.

[0020] Compared with the prior art, the present application has the following advantages: 1. The nutritional composition of the present application can effectively maintain the alpha diversity stability of the intestinal flora at each stage of the pregnancy period (including the early pregnancy period, the middle pregnancy period, and the late pregnancy period) by optimizing the ratio of prebiotics to protein and reasonably adjusting the ratio of plant protein to animal protein. The experimental results show that the shannon index at each stage remains at a relatively stable level, indicating that the bacterial diversity is well maintained.

[0021] 2. The nutritional composition of the present application is beneficial to maintaining the relative stability of the intestinal dominant flora during the pregnancy period and the increase of the specific bifidobacterium, thereby maintaining the maternal metabolic homeostasis and providing immune protection for the newborn. The experimental results show that the types of the intestinal dominant flora are roughly the same at different stages of the pregnancy period, and are composed of the Clostridium genus ( g_Coprococcus ), the Ruminococcus genus ( g_[Ruminococcus]_torques_group ), the Faecalibacterium genus ( Faecalibacterium ), the Roseburia genus ( Roseburia ), the Blautia genus ( Blautia ), and the like. These genera maintain a relatively stable proportion during the whole pregnancy period, and the stable distribution of the dominant flora helps to ensure the normal physiological function and microecological balance of the intestinal tract. In addition, the relative abundance of the bifidobacterium increases in the late pregnancy period (LP stage) and the lactation period (PP stage). The increase in the number of bifidobacterium, as a kind of probiotic, can promote intestinal peristalsis, synthesize vitamins, and enhance the intestinal barrier function, thereby adapting to the needs of the maternal physiological changes in the late pregnancy period and the lactation period, such as improving the digestive and absorptive capacity of nutrients and regulating the immune system.

[0022] 3. The nutritional composition of the present application is beneficial to improving the birth outcome of the newborn, reducing developmental retardation, and reducing the rate of premature birth and low birth weight. This indicates that the nutritional composition of the present application can effectively promote the growth and development of infants and young children, significantly reduce the risk of developmental retardation, and at the same time, ensure the normal development of the fetus while avoiding the occurrence of abnormal body weight. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 Shannon index during early pregnancy, mid-pregnancy, late pregnancy and postpartum period; Figure 2 Bacterial community distribution diagram during early pregnancy, mid-pregnancy, late pregnancy and postpartum period; Figure 3 Comparison chart of growth and development retardation rate of infants in the project and infants three years before the project; Figure 4 Column chart of the average incidence of premature birth of newborns in each project county and the average incidence of premature birth of newborns in each project county; Figure 5 Comparison chart of the average incidence of premature birth of newborns in each project county and the average incidence of premature birth of newborns in China in 2012; Figure 6 Column chart of the average incidence of low birth weight of newborns in each project county and the average incidence of low birth weight of newborns in each project county; Figure 7 Comparison chart of the average incidence of low birth weight of newborns in each project county and the average incidence of low birth weight of newborns in China in 2019. DETAILED DESCRIPTION

[0024] The present application will be further described below in conjunction with specific examples, so that those skilled in the art can better understand the present application and implement it. The examples are not intended to limit the present application.

[0025] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description of the application herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0026] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description of the application herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0027] In the following specific embodiments, *p represents comparison with the blank control group, *p<0.05. Materials, instruments and detection methods

[0028] 1. Materials and instruments Table 1

[0029] 2. Detection method (1) Bacterial DNA extraction and amplification The detection material is a fecal sample. 200 mg of the fecal sample is taken for DNA extraction. The TIANamp Stool DNA Kit is used to extract total DNA. 1% concentration agarose gel electrophoresis is used for detection. The NanodropTM 2000 ultramicro spectrophotometer is used for DNA concentration and purity determination.

[0030] The 16S rRNA gene V3-V4 region (341F-806R) of the extracted bacterial DNA is PCR amplified, and 3 replicates are set for each sample. The amplification primer sequences are shown in Table 2.

[0031] Table 2

[0032] The PCR reaction system is established: DNA template 10 ng, upstream primer (5 mol / L) 0.8 L, downstream primer (5 mol / L) 0.8 L, Phusion high-fidelity DNA polymerase, 0.4 L dNTPs mxi (2.5 mmol / L), 2 L PCR buffer (5×), 4 L BSA 0.2 L ddH2O supplemented to 20 L; The amplification conditions are: 95°C pre-denaturation for 3 min; 95°C denaturation for 30 s; 55°C annealing for 30 s; 72°C extension for 45 s, a total of 30 cycles, and 72°C terminal extension for 8 min. PCR instrument: ABI GeneAMP® 9700 type. The PCR amplification product is detected by 2% ethidium bromide agarose gel electrophoresis. The AxyPrep DNA gel recovery kit is used to cut and recover the DNA product and purify it. The product is subjected to QuantiFluorTM-ST micro fluorescence agent for DNA quantitative determination.

[0033] (2) Library construction and sequencing The Nextera XT DNA Sample Preparation Kit library construction kit is used to construct the sequencing library. The Qubit and Q-PCR are used to quantify the constructed library. After determining that the library is qualified, the Illumina NovaSeq 6000 sequencing platform is used to perform PE250 double-end sequencing on the library.

[0034] (3) Sequencing data processing According to the PCR amplification primer sequence and the Barcode sequence, the sample data was split from the data obtained, and after cutting off the primer and Barcode sequence, the Reads of the sample were spliced using FLASH2 (Version 2.2.00), and the spliced sequence was the Raw Tags data. Through strict filtering, high-quality Tags data (Clean Tags) were obtained.

[0035] According to the Tags quality control process of QIIME (Version 2.0), the following operations were performed: a) Tags cutting: the Raw Tags were cut off from the first low-quality base site with continuous low-quality values (the default quality threshold was ≤20) and the base number reached the set length (the default length value was 3); b) Tags length filtering: the Tags data set obtained after cutting the Tags was further filtered to remove Tags with a continuous high-quality base length less than 75% of the Tags length. The processed Tags sequence was compared and detected with the species annotation database, and finally the chimeric sequence was removed to obtain the effective data (Effective Tags).

[0036] Example 1 The present embodiment provides a nutritional composition composed of whey protein, soy protein and resistant dextrin; in the nutritional composition, the mass ratio of whey protein, soy protein and resistant dextrin is 1:5:0.686.

[0037] Examples 2-3 and Comparative Examples 1-5 Examples 2-3 and Comparative Examples 1-5 differ from Example 1 in that the components and their proportions in the nutritional composition (animal protein, plant protein and resistant dextrin) are different, as shown in Table 3.

[0038] Table 3

[0039] Experiment 1: Rat experiment 1. Experimental animals and grouping Select 90 SPF female rats of 8 weeks of age and 90 SPF male rats of 8 weeks of age; set up 9 groups, 10 pregnant rats in each group. All groups were intervened from confirmation of pregnancy (GD0) to 21 days after delivery.

[0040] Raising conditions: the animals were raised in a barrier environment, the indoor temperature was 25±1℃, the humidity was 45±5%, the animals were free to drink water in the facility, and were raised in a 12h light-dark alternating environment per day. The animals were adapted to standard feed for 1 week. Female and male rats were caged at a ratio of 1:1 (GD0), and the next morning vaginal smears were checked to determine the presence of sperm as the first day of pregnancy, which was the starting point for intragastrical intervention. The female rats were continuously intragastrically administered until the offspring were weaned. The experimental group was administered with the sample solution at a corresponding dose according to the animal grouping, and the control group was administered with normal saline at a corresponding dose. The animals were intragastrically administered once a day for 6 consecutive weeks, and the animals in each dose group were given maintenance feed. The specific doses of the control group and the intervention group are shown in Table 4 below.

[0041] Table 4

[0042] Fresh feces of each female rat was collected in a clean environment before intragastrical administration, in the early pregnancy (EP), in the middle pregnancy (MP), in the late pregnancy (LP), and after delivery (PP), and was numbered and stored at -80℃ for intestinal flora sequencing. The delivery start time was accurately recorded by infrared monitoring from GD18. The offspring counting and body weight measurement were completed within 12 hours after delivery.

[0043] 2. Monitoring index 2.1 Female rat index The feces of the female rats at each stage were subjected to intestinal flora sequencing to obtain the Shannon index of the intestinal flora of the female rats at each stage, as shown in Table 5.

[0044] Table 5

[0045] As can be seen from Table 5, compared with before intragastrical administration, the diversity of the flora of the rats in group A (blank control group) decreased slightly in the early pregnancy (EP); the flora disorder reached a peak in the middle pregnancy (MP) and the late pregnancy (LP), and the diversity was the lowest; and the diversity of the flora recovered and increased in the postpartum period (PP).

[0046] Compared with the blank control group, the intestinal flora of the rats in groups B-D showed different change rules due to the intragastrical administration of the nutritional composition of examples 1-3. Compared with before intragastrical administration, the flora of the rats did not disorder in the early pregnancy (EP), and the diversity increased slightly; in the middle pregnancy (MP) and the late pregnancy (LP), the diversity of the intestinal flora of the rats was significantly improved; in the postpartum period (PP), the diversity of the flora further increased. This indicates that the nutritional composition provided by the present application can reverse the intestinal flora disorder of the rats in the pregnancy period and after delivery, and significantly improve the intestinal flora diversity in the pregnancy period and after delivery.

[0047] The intestinal flora of the rats in the E~G group, which were respectively administered the nutritional composition of Comparative Examples 1~3, showed similar variation patterns as the blank control group: the intestinal flora diversity slightly decreased in the early pregnancy (EP), and the intestinal flora further became unbalanced in the middle pregnancy (MP) and the late pregnancy (LP), and the diversity reached the minimum, but the diversity of the intestinal flora was still significantly higher than that of the blank control group; the intestinal flora had a certain rebound after delivery (PP), but the diversity was still lower than that before administration. This indicates that the whey protein, soy protein and prebiotics in the nutritional composition of the present application are all critical and indispensable, and the absence of any one of them will significantly reduce the effect of maintaining the intestinal flora diversity stable during pregnancy.

[0048] The intestinal flora of the rats in the H and I groups, which were respectively administered the nutritional composition of Comparative Examples 4~5, showed similar variation patterns as the E~G group: the intestinal flora became unbalanced in the early pregnancy (EP), the middle pregnancy (MP) and the late pregnancy (LP), and the diversity of the intestinal flora had a certain rebound after delivery (PP), but was still lower than that before administration. This indicates that the whey protein, soy protein and prebiotics in the nutritional composition of the present application need to be controlled within the ratio range of 1:(3~6):(0.5~0.8), and if the ratio exceeds this range, the effect of maintaining the intestinal flora diversity stable during pregnancy will also be significantly reduced.

[0049] 2.2 Body weight of newborn rats The body weight of the newborn rats was weighed within 12 hours after the mother rats gave birth, the average birth weight, SGA and low birth weight rate of the newborn rats were counted, and the results are shown in Table 6. Among them, the newborn rats with a body weight lower than the average body weight of the same litter by 2 standard deviations were defined as low birth weight individuals, i.e., the average value and standard deviation of the birth weight of all surviving newborn rats in the same litter were first calculated, and the individuals lower than (average value-2*standard deviation) were defined as the "low birth weight" individuals of the litter.

[0050] Table 6

[0051] As shown in Table 6, the low birth weight rate of the newborn rats in the A group (blank control group) reached 12.99%, and the low birth weight rate of the newborn rats in the B~D groups was between 3~5%, which was significantly lower than that of the blank control group, which indicates that after being administered the nutritional composition of the present application, the birth outcome of the newborn rats can be effectively improved, and the low birth weight rate can be reduced.

[0052] The low birth weight rate of the newborn rats in the E~I groups was between 8~11%, which was lower than that of the blank control group, but was still significantly higher than that of the B group. This indicates that the whey protein, soy protein and prebiotics in the nutritional composition of the present application are indispensable, and need to be controlled within the ratio range of 1:(3~6):(0.5~0.8), so as to significantly reduce the low birth weight rate.

[0053] 2.3 Preterm rat number The preterm rat number was counted by infrared monitoring from GD18, and the starting time of parturition of the mother rat was recorded accurately. The results are shown in Table 7. Among them, the normal gestation period of the mother rat is 21-23 days, and the definition of the delivery of the baby rat before gestation 21 days is preterm birth.

[0054] Table 7

[0055] Referring to Table 7, the preterm birth rate of the baby rat in group A (blank control group) reached 18.18%; and after the mother rats in groups B-D were gavaged with the nutritional composition of Examples 1-3, the preterm birth rate of the baby rat was between 8-11%, which was significantly lower than that of the blank control group. This shows that after gavaging with the nutritional composition of the application, the birth outcome of the baby rat can be effectively improved, and the preterm birth rate is reduced.

[0056] After the mother rats in groups E-I were gavaged with the nutritional composition of Comparative Examples 1-5, the preterm birth rate of the baby rat was between 14-16%, which was lower than that of the blank control group, but still significantly higher than that of group B. This shows that in the nutritional composition of the application, whey protein, soy protein and prebiotics are indispensable, and must be controlled within the ratio range of 1:(3-6):(0.5-0.8), which can significantly reduce the preterm birth rate.

[0057] Experiment two: pregnant woman intervention experiment An intervention experiment was conducted on 10,000 pregnant women. The intervention population was women from 3 months before pregnancy to 6 months after childbirth. The population was selected from 16 project sites in 7 provinces and regions, which were Zhangxian County of Dingxi City in Gansu Province, Xixihe County of Longnan City in Gansu Province, Weicheng County of Chengde City in Hebei Province, Fengning County of Chengde City in Hebei Province, Xingguo County of Ganzhou City in Jiangxi Province, Fangxian County in Hubei Province, Chifeng City in Inner Mongolia Autonomous Region, Kalaqin Banner in Inner Mongolia Autonomous Region, Ningcheng County in Inner Mongolia Autonomous Region, Shenqiu County in Henan Province, Fanxian County in Henan Province, Gushi County in Henan Province, Huaiyang District in Henan Province, Taiqian County in Henan Province, Guangshan County in Henan Province, and Yingshang County in Anhui Province. The pregnant women enrolled in the group took additional nutritional supplements under normal diet. The nutritional supplement was 15g per pack, and the dosage was one pack per day. The composition of the nutritional supplement is shown in Table 8.

[0058] Table 8

[0059] 1. Intestinal flora test The pregnant women were continuously sampled at a proportion of 10% and the intestinal flora of the mother and baby was detected. The detection time points were the pregnant women (early pregnancy, mid-pregnancy, late pregnancy) and the baby (three months after birth, six months after birth), and each pregnant woman collected fecal samples in a sterile fecal collection tube according to the time point and quickly delivered them to the hospital-80℃ for storage, and then unifiedly mailed to the detection unit for detection. The experimental results are shown in Table 9, Figures 1-2 .

[0060] Table 9

[0061] Please refer to Table 9 and Figure 1 , after the pregnant women in the group were intervened with the nutritional supplement of Example 1, the alpha diversity of the intestinal flora at each stage of pregnancy (including early pregnancy, mid-pregnancy, and late pregnancy) could be effectively maintained. According to the experimental data, the average shannon value of early pregnancy (EP) was 3.71, mid-pregnancy (MP) was 3.79, late pregnancy (LP) was 3.80, and postpartum (PP) was 3.77. The shannon index at each stage remained at a relatively stable level, indicating that the diversity of the flora was well maintained.

[0062] Please refer to Figure 2 , at different stages of pregnancy, the dominant flora in the intestinal tract was roughly the same, and was composed of Clostridium spp. g_Coprococcus , Ruminococcus spp. g_[Ruminococcus]_torques_group , Faecalibacterium spp. Faecalibacterium , Roseburia spp. Roseburia , and Blautia spp. Blautia These genera maintained a relatively stable proportion throughout pregnancy, such as Faecalibacterium, which accounted for 0.2-0.3 throughout pregnancy, Roseburia for 0.2-0.25, and Blautia for 0.25-0.3. The stable distribution of these dominant flora helps to ensure the normal physiological function and microecological balance of the intestinal tract.

[0063] In addition, it can also be seen from Figure 2 that the relative abundance of Bifidobacterium increased in the late pregnancy (LP stage) and lactation period (PP stage). As a probiotic, the increase in the number of Bifidobacterium can promote intestinal peristalsis, synthesize vitamins, and enhance intestinal barrier function, thereby adapting to the needs of maternal physiological changes in the late pregnancy and lactation period, such as improving the ability to digest and absorb nutrients and regulating the immune system.

[0064] Therefore, the nutritional supplement of Example 1, through the strategy of maintaining the stability of core genera during pregnancy and childbirth + specific increase of Bifidobacterium in the late pregnancy, not only maintains the metabolic homeostasis of the mother, but also provides immune protection for the newborn.

[0065] 2. Statistics of the birth outcome of the newborn Please see Figure 3 Statistics show that the incidence of growth retardation in infants at 42 days of age was 0.14%, an overall improvement of 91% compared to the average growth retardation rate in the three years prior to the project. The incidence of growth retardation at 6 months of age was 0.32%, an overall improvement of 68% compared to the average growth retardation rate in the three years prior to the project. This indicates that the nutritional composition of the present invention can effectively promote the growth and development of infants and significantly reduce the risk of developmental delays.

[0066] Please see Figures 4-5 The overall average incidence of premature birth in the project area was 3.94%, while the average incidence of premature birth in China in 2012 was 5.9%. Calculations show that the county-level data represents a decrease of approximately 33.22% compared to the national average. This result fully demonstrates that this nutritional composition can effectively reduce the incidence of premature birth and improve the birth quality of newborns.

[0067] Please see Figures 6-7 The overall low birth weight incidence rate among newborns in the project area was 2.08%, while the average incidence rate in China in 2019 was 3.24%. Calculations show that the county-level data represents a decrease of approximately 35.80% compared to the national average. This indicates that the composition can ensure normal fetal development while preventing abnormal birth weight.

[0068] The above-described embodiments are merely preferred embodiments provided to fully illustrate the present invention, and the scope of protection of the present invention is not limited thereto. Equivalent substitutions or modifications made by those skilled in the art based on the present invention are all within the scope of protection of the present invention. The scope of protection of the present invention is defined by the claims.

Claims

1. A nutritional composition, characterized in that, animal protein, plant protein and prebiotics; a mass ratio of the animal protein, the plant protein and the prebiotics in the nutritional composition is 1: (3-6): (0.5-0.8).

2. The nutritional composition according to claim 1, characterized in that, The animal protein comprises whey protein; the plant protein comprises soy protein; and the prebiotics are selected from any one or combination of resistant dextrin, fructo-oligosaccharide, galacto-oligosaccharide, inulin, polydextrose, xylo-oligosaccharide and resistant starch.

3. The nutritional composition of claim 1, wherein, The mass ratio of the animal protein, the plant protein and the prebiotics in the nutritional composition is 1:5:0.

686.

4. Use of the nutritional composition of any one of claims 1-3 in the preparation of a product for maintaining the stability of intestinal flora diversity during pregnancy.

5. Use of the nutritional composition of any one of claims 1-3 in the preparation of a product for improving the birth outcome of a newborn.

6. Use according to claim 5, characterized in that, The birth outcome of the newborn comprises at least one of (i)-(iii): (i) developmental retardation; (ii) premature birth; (iii) low birth weight.

7. A nutritional supplement for pregnant women, characterized in that, The nutritional supplement comprises the nutritional composition of any one of claims 1-3; and fats, carbohydrates, sodium, vitamin A, vitamin B, vitamin C, vitamin D, folic acid, calcium, iron, zinc and DHA; wherein the vitamin B comprises vitamin B1, vitamin B2, vitamin B6 and vitamin B12.

8. A nutritional supplement for pregnant women as claimed in claim 7, wherein, Each 15 g of the nutritional supplement comprises 3.5-4 g of the nutritional composition, 1-2 g of fat, 8-9 g of carbohydrate, 30-35 mg of sodium, 400-600 ug of vitamin A, 1-1.5 mg of vitamin B1, 1-1.5 mg of vitamin B2, 1-2 mg of vitamin B6, 2-3 ug of vitamin B12, 80-120 mg of vitamin C, 6-8 ug of vitamin D, 150-250 ug of folic acid, 300-500 mg of calcium, 10-15 mg of iron, 6-9 mg of zinc and 60-70 mg of DHA.

9. A nutritional supplement for pregnant women as claimed in claim 8, wherein, Each 15 g of the nutritional supplement comprises 3.9 g of the nutritional composition, 1.5 g of fat, 8.5 g of carbohydrate, 31 mg of sodium, 500 ug of vitamin A, 1.2 mg of vitamin B1, 1.2 mg of vitamin B2, 1.5 mg of vitamin B6, 2.5 ug of vitamin B12, 100 mg of vitamin C, 6.5 ug of vitamin D, 200 ug of folic acid, 400 mg of calcium, 12 mg of iron, 7.5 mg of zinc and 65 mg of DHA.

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