CN116725079A - Formula powder rich in breast milk oligosaccharide for regulating infant intestinal microorganism composition and promoting short chain fatty acid production and preparation method thereof - Google Patents

Abstract

The invention discloses a formula powder rich in breast milk oligosaccharide, which is used for improving the intestinal microorganism composition of infants and promoting the production of short-chain fatty acid. The formula powder can improve intestinal microorganism composition by only adding 2' fucosyllactose, especially beneficial bacteriaBlautia、OlsenellaAbundance, increased production of short chain fatty acids (acetic acid and propionic acid, butyric acid). In addition, the formula improves immune function and promotes the level of the anti-inflammatory cytokine IL-10.

Description

Regulate the intestinal microbial composition of infants and young children and promote the production of short-chain fatty acids. Milk oligosaccharide formula powder and preparation method thereof

Technical field

The present invention relates to a new application of breast milk oligosaccharides, specifically, to the application of breast milk oligosaccharides in the preparation of infant formula powder with the effect of improving intestinal microenvironment health (especially reducing intestinal branched chain fatty acids). , as well as the prepared infant formula powder and related preparation methods.

Background technique

The period of infancy and early childhood is a critical period for physical and intellectual development. Breast milk, as the gold standard for infant nutrition formula, is the safest and most natural food for infants and young children. It not only contains a variety of immune proteins and growth factors, but also contains breast milk oligosaccharides with complex components but diverse functions. Due to various reasons, some babies are unable to consume sufficient amounts of breast milk. Therefore, infant formula that simulates the nutritional content of breast milk as much as possible has become the first choice of nutritional substitutes. Due to the complex composition and wide variety of breast milk oligosaccharides, it is not possible to synthesize all of them artificially. Currently, there are two ingredients that can be synthesized and used abroad: 2’-fucosyllactose (2’-FL) and lacto-N-eotetraose (LNnT).

Human Milk Oligosaccharides (HMOs for short) are the third most abundant substance in breast milk after lactose and fat. Its total content changes at various stages of lactation. It is about 12-14g/L in mature milk and about 20-24g/L in colostrum. The structure of each breast milk oligosaccharide has a lactose at the reducing end, most of which use polylactosamine as the structural backbone, and contain fucose, sialic acid, or both at the chain end. Breast milk oligosaccharides are mainly composed of three major categories: fucosyl oligosaccharides, with 2'-fucosyl oligosaccharides and 3'-fucosyl oligosaccharides as representative substances; sialic acid-based oligosaccharides Oligosaccharides, with 3'-sialyllactose and 6'-sialyllactose as representative substances; oligosaccharides formed from a core sugar chain structure that does not contain fucosyl or sialic acid groups, with lactose- N-tetraose and lactose-N-neotetraose are representative substances. The presence and content of HMOs vary among individuals and are related to the Lewis secretory composition of the nursing mother. Since the raw material of infant formula powder is usually cow's milk, and milk usually does not contain or contains very few such oligosaccharide substances (Table 1), HMOs have become a hurdle that infant formula powder must overcome if it wants to be closer to the ingredients of breast milk. A chasm.

Table 1 Contents of macronutrients and HMOs in mature breast milk and cow’s milk

Intestinal flora is an important factor affecting various physiological functions of the human body. It can affect the entire life cycle of the host since its establishment in early life. After birth, the infant intestine undergoes a complex process of microbial colonization. Studies have shown that feeding style is a key factor in regulating the composition and metabolic function of the gastrointestinal microbiota. Breastfed babies have a more stable microbial community (Bifidobacterium is the dominant flora) during the first week of life, which plays an important role in maintaining the health of the newborn. Intestinal flora is an important component of the human intestinal microecological system and plays an important role in human health. Anaerobic Bacteroidetes, Bifidobacteria, Eubacteria, Streptococci and Lactobacilli in the intestinal flora can release metabolite short chain fatty acids (SCFA) by fermenting carbohydrates, proteins and lipids. Mainly include acetic acid, propionic acid and butyric acid. SCFA can regulate a variety of physiological functions of the body and plays an important role in regulating the health of the intestinal microenvironment. For example, SCFA can provide energy and regulate electrolytes, acetic acid is an important source of energy for the host, propionic acid can participate in the process of reverse conversion of pyruvate into glucose, and butyric acid is taken up by epithelial cells and is the main energy source of epithelial cells. SCFA also has anti-inflammatory, improved intestinal barrier function and antibacterial effects. SCFA released by intestinal flora fermentation can reduce intestinal pH, thereby increasing the growth of beneficial bacteria in the intestine and reducing the proliferation of harmful bacteria.

The research of Chow et al. also showed that when fermentable carbohydrates are not present in the fecal culture system of breast-fed and formula-fed infants and young children, metabolites of protein fermentation will be mainly produced; and when various fermentable carbohydrates are added, , HMO-like carbohydrates, the contents of these protein metabolites decreased again. The higher short-chain fatty acids in the feces of the formula-fed group may have an impact on the metabolism of infants and young children. Thompson-Chagoyan et al studied 92 infants aged 2 to 12 months, half of whom were non-allergic and half of whom had cow's milk protein allergy symptoms. Infants with cow's milk protein allergy have higher fecal branched-chain fatty acid concentrations and proportions than healthy infants.

At present, breast milk oligosaccharides are gradually being paid attention to by research on maternal and infant nutrition and health. However, there are many types of breast milk oligosaccharides, complex structures, and the concentrations of various breast milk oligosaccharides vary widely. Therefore, it is necessary to prepare a kind of oligosaccharide that can improve the health of the intestinal microenvironment. , Infant formula powder that can be mass-produced is very necessary.

Contents of the invention

One object of the present invention is to provide a breast-milked infant formula powder that can improve the intestinal microbial composition of infants and promote the production of short-chain fatty acids and is easy to produce.

In order to solve the above technical problems, the technical solutions adopted by the present invention are:

The invention discloses an optimization idea for breast-milked infant formula powder that can improve the intestinal microbial composition of infants and promote the production of short-chain fatty acids. It includes the following approaches, characterized in that, one: the breast milk-rich oligosaccharide is fucosyllactose. Second: The improvement of intestinal microbial composition includes: enriching beneficial bacteria Blautia and Olsenella in the intestine. Third, the promotion of the production of short-chain fatty acids includes: increasing the production of short-chain fatty acids (acetic acid, propionic acid, and butyric acid). Fourth: This formula powder can also improve immune function, promote the level of the anti-inflammatory cytokine IL-10, and reduce the level of IL-4.

Preferably, 80-100 parts of breast milk oligosaccharide 2'-FL, 5000-7000 parts of fresh milk, 1000-2000 parts of desalted whey powder, 2-3 parts of DHA powder, 3-7 parts of ARA powder, and 200 parts of OPO structural lipid -300 parts, flaxseed oil 15-40 parts, coconut oil 50-80 parts, sunflower oil 150-200 parts, soy lecithin 20-40 parts, lactose 150-400 parts, compound minerals 2-4 parts, complex Contains 2-4 parts of vitamins and 1-2 parts of mixed nutrients.

More preferably, 90 parts of breast milk oligosaccharides, 6000 parts of fresh milk, 1500 parts of desalted whey powder, 2.5 parts of DHA powder, 5 parts of ARA powder, 250 parts of OPO complex fat, 26 parts of flaxseed oil, 65 parts of coconut oil, 180 parts of sunflower oil, 30 parts of soy lecithin, 250 parts of lactose, 3 parts of compound minerals, 3 parts of compound vitamins, and 1 part of compound mixed nutrients.

More preferably, it contains breast milk oligosaccharides 14.2-3182.2 mg/100g, and the protein content of the infant formula powder is 1.46±0.07g/100mL, the fat content is 3.41±0.04 g/100mL, and the lactose content is 7.03± 0.02g/100mL, total solid content is 13.00±0.00 g/100mL.

The human milk oligosaccharide is 2'-FL.

Preferably, the formula powder rich in breast milk oligosaccharides also includes one or more of DHA, ARA, OPO structural lipids, vitamins, minerals, and nutrients in its raw materials.

A method for preparing formula powder rich in breast milk oligosaccharides, which adopts a wet or dry production process to mix breast milk oligosaccharides with other raw materials in the formula to prepare the infant formula powder.

Preferably, each portion of the compound vitamins contains: vitamin A: 100-150 μg RE; vitamin D: 2.0-3.5 μg; vitamin E: 2.5-6.0 mg; vitamin K1: 9-13 μg; vitamin B1: 130-180 μg ; Vitamin B2: 300~450μg; Vitamin B6: 65~80μg; Vitamin B12: 0.2~1.2μg; Inositol: 8.5~13μg; Folic acid: 8~17μg; Pantothenic acid: 600~1800μg; Vitamin C: 15~32μg; Biological Phytophytes: 3.5~5.6μg, lutein 28~50μg;

Preferably, each portion of the compound minerals contains: magnesium: 10.1-12.9 mg; iron: 2.1-4.4 mg; zinc: 1-3 mg; manganese: 65-85 μg; iodine: 47.8-89.5 μg; copper: 50 ~125μg; selenium: 3.5~7.0μg, chromium 0.3~0.8μg, molybdenum 0.6~2μg;

Preferably, each portion of the compound mixed nutritional supplement contains: 11 to 23 mg of nucleotides, 45 to 56 mg of choline, 8.5 to 17.0 mg of taurine, and 2.5 to 6.0 mg of L-carnitine;

Preferably, the formula powder rich in breast milk oligosaccharides contains 82.2 mg/100g of breast milk oligosaccharides, and the protein content of the infant formula powder is 1.46±0.07g/100mL, and the fat content is 3.41±0.04 g. /100mL, the lactose content is 7.03±0.02 g/100mL, and the total solid content is 13.00±0.15 g/100mL.

The invention also discloses a preparation method, which includes the following steps:

Step 1: Raw milk undergoes acceptance, pretreatment, sterilization, then pasteurization at 85-92°C for 15-20 seconds, cooled to 4°C, and stored at <4°C;

Step 2, ingredients: use raw goat milk as the base material, add breast milk oligosaccharides, desalted whey powder, ARA powder, DHA powder, lactose and compound vitamins, minerals and nutrients into the ingredient tank, and finally add OPO compound fat, sunflower oil, coconut oil, flax oil, and the resulting milk is premixed at 60±5℃;

Step 3: Homogenization: The premixed liquid is subjected to secondary homogenization at 60±5°C. The primary homogenization pressure is 10-20Mpa and the secondary homogenization pressure is 2-3Mpa. After homogenization, cool to below 6°C, keep the pH value of the material at 6.70-6.90, and store it in a temporary storage tank;

Step 4, sterilization: Use pasteurization at a temperature >80°C. The optimal temperature is 86-92°C, 20-60S. Basis: This temperature combination helps to control the microorganisms of the product and can form some natural antioxidants to control the functional properties of the milk powder;

Step five, concentration and drying: The sterilized milk is concentrated through a three-effect evaporator to a dry matter content of 45-55%; the concentrated liquid is dried through a spray drying tower, and the air inlet temperature is 186°C-215 ℃; dry exhaust temperature: 72-91 ℃. When the negative pressure of the drying tower is normal: -0.03 Mpa ~ -0.58 Mpa, the milk powder particles can be adjusted by adjusting the high-pressure pump pressure, nozzle size and agglomeration tube angle.

Step six, fluidized bed cooling and screening: fluidized bed section I, II, and III temperature: 15-95°C; fluidized bed section IV temperature: 15-40°C. Cool and then sieve.

Step seven, packaging and testing.

Description of drawings

Figure 1 The regulatory effect of formula powder rich in human milk oligosaccharides on the composition of intestinal microorganisms at the phylum and genus levels.

Figure 2 Formula rich in breast milk oligosaccharides shapes gut microbiota biomarker categories.

Figure 3 The regulatory effect of formula powder rich in breast milk oligosaccharides on the abundance of specific bacterial genera of intestinal microorganisms.

Figure 4 The regulatory effect of formula powder rich in breast milk oligosaccharides on intestinal short-chain fatty acid metabolism.

Figure 5 The regulatory effect of formula powder rich in breast milk oligosaccharides on immune function-related cytokines.

Detailed ways

The present invention will be further described below in conjunction with specific embodiments.

Prepare the following substances in advance:

Compound minerals: Each serving contains: Magnesium: 10.1~12.9mg; Iron: 2.1~4.4mg; Zinc: 1~3mg; Manganese: 65~85μg; Iodine: 47.8~89.5μg; Copper: 50~125μg; Selenium: 3.5～7.0μg, chromium 0.3～0.8μg, molybdenum 0.6～2μg;

Compound vitamins: Each serving contains: Vitamin A: 100~150μg RE; Vitamin D: 2.0~3.5μg; Vitamin E: 2.5~6.0mg; Vitamin K1: 9~13μg; Vitamin B1: 130~180μg; Vitamin B2: 300 ~450μg; Vitamin B6: 65~80μg; Vitamin B12: 0.2~1.2μg; Inositol: 8.5~13μg; Folic acid: 8~17μg; Pantothenic acid: 600~1800μg; Vitamin C: 15~32μg; Biotin: 3.5~5.6 μg, lutein 28-50 μg;

Compound mixed nutritional supplement: Each serving contains: 11 to 23 mg of nucleotides, 45 to 56 mg of choline, 8.5 to 17.0 mg of taurine, and 2.5 to 6.0 mg of L-carnitine.

Example 1

The preparation steps of formula powder rich in breast milk oligosaccharides are as follows:

Step 1: Raw milk undergoes acceptance, pretreatment, sterilization, then pasteurization at 85-92°C for 15-20 seconds, cooled to 4°C, and stored at <4°C;

Step 2, ingredients: Add 90 kg of breast milk oligosaccharide 2'-FL, 6000 g of raw milk, 1500 kg of desalted whey powder, 2.5 kg of DHA, 5 kg of ARA powder, 26 kg of flaxseed oil, and coconut oil in the ingredient tank. 65 kg, 180 kg of sunflower oil, 30 kg of soy lecithin, 250 kg of lactose, 3 kg of compound minerals, 3 kg of compound vitamins, 1 kg of compound mixed nutrients, and finally add 250 kg of OPO structural fat to obtain milk Premix at 60±5℃;

Step 3: Homogenization: The premixed liquid is subjected to secondary homogenization at 60±5°C. The primary homogenization pressure is 10-20Mpa and the secondary homogenization pressure is 2-3Mpa. After homogenization, cool to below 6°C, keep the pH value of the material at 6.70-6.90, and store it in a temporary storage tank;

Step 4, sterilization: Use pasteurization at a temperature >80°C. The optimal temperature is 86-92°C, 20-60S. Basis: This temperature combination helps to control the microorganisms of the product and can form some natural antioxidants to control the functional properties of the milk powder;

Step five, concentration and drying: The sterilized milk is concentrated through a three-effect evaporator to a dry matter content of 45-55%; the concentrated liquid is dried through a spray drying tower, and the air inlet temperature is 186°C-215 ℃; dry exhaust temperature: 72-91 ℃. When the negative pressure of the drying tower is normal: -0.03 Mpa ~-0.58 Mpa, adjust the milk powder particles by adjusting the high-pressure pump pressure, nozzle size and agglomeration tube angle;

Step six, fluidized bed cooling and screening: fluidized bed section I, II, and III temperature: 15-95°C; fluidized bed section IV temperature: 15-40°C. Cool and then sieve.

Step seven, packaging and testing.

After testing, the content of each ingredient in the milk powder meets the requirements. The 2'-FL content of breast milk oligosaccharides is 14.2-3182.2 mg/100g, and the protein content of the infant formula powder is 1.46±0.07g/100mL, the fat content is 3.41±0.04 g/100mL, and the lactose content is 7.03± 0.02 g/100mL, total solid content is 13.00±0.15 g/100mL.

Example 2

In vivo experimental design to verify the efficacy of breast milk oligosaccharide-enriched formula powder:

Five-week-old C57BL/6J male mice (n = 48) were raised in a controlled environment. Four animals were assigned to each standard cage and had free access to standard laboratory food and water. The entire experimental environment was set to a 12-hour light-dark cycle, with the temperature maintained at 22±2°C and the humidity 45±5%. Before the start of the experiment, the mice had to undergo a week of acclimatization. All mice received human care, and all experiments were reviewed and approved by the Animal Care and Welfare Committee of Northeast Agricultural University, and the approval protocol number is NEAUEC20210407. All powder samples were stored in drying dishes at room temperature (25°C) for later use. The contents of the main ingredients in formula powder IF and human milk are shown in Table 2.

Table 2 Main ingredients of the formula (g/100mL)

After 1 week of adaptation, mice were randomly divided into control group (named NAB-NFMT-PBS) (n=8) and antibiotic group (n=40). The following week, the mice in the control group were allowed to drink normal water, while the mice in the antibiotic group were allowed to drink antibiotic solution. All antibiotic solutions were prepared by adding ampicillin, cefoperazone sodium salt, and clindamycin hydrochloride to drinking water, each at a concentration of 1 mg/mL. Mannitol was injected within 2 days after stopping antibiotic treatment, and the control group continued to drink water normally.

Then enter the formal experimental cycle, which lasts for 4 weeks. Antibiotic-treated mice were randomly divided into two groups, untransplanted infant feces samples (named AB-NFMT-PBS) group (n =8) and transplanted infant feces samples (AB-FMT) group (n =32), all Mice were orally administered infant fecal slurry. The AB-FMT group was administered fecal bacterial suspension (200 μL) every 2 days for infant intestinal microbial transplantation. Prepare FMT by mixing 5 g of infant feces with 5 mL of sterile PBS solution and homogenizing immediately. Rapidly collect infant fecal samples under anaerobic conditions. In the AB-NFMT-PBS group, the same amount of PBS solution was administered intragastrically.

The mice in the AB-FMT group were randomly divided into the AB-FMT-IF group (200 μL of IF without 2′-FL added per day) and the AB-FMT-2′-FL/IF group (200 μL of IF added with 2′-FL per day). IF) and AB-FMT-hm group (200 μL human milk per day), 8 animals in each group. Mice in the AB-FMT-2'-FL/IF group were orally administered 2'-FL (20 mg/mL). IF and human milk powder were formulated into specific concentrations and pasteurized, and then administered to the corresponding groups by gavage every day. At the same time, the AB-FMT-PBS group was used as a reference, and the same amount of sterilized PBS was administered intragastrically.

After the experiment, all mice were fasted for 16 hours and humanely killed with ether. Take the whole blood of mouse eyeballs and centrifuge (1000×g) at 4°C to obtain serum. The serum is stored at -80°C, with one part used to detect immune indicators and the other part used to detect clinical biochemical indicators. Collect the intestinal contents with sterile tin foil, place them in sterile freezing tubes, quickly freeze them with liquid nitrogen, and store them in a -80°C low-temperature refrigerator for further analysis of intestinal microorganisms and short-chain fatty acids.

The intestinal microbiome was analyzed by DNA extraction and high-throughput 16SrRNA gene sequencing, and the concentration of short-chain fatty acids (acetic acid, propionic acid, and butyric acid) in feces was detected using a R&F 9720 gas chromatograph.

Example 3

Regulation of intestinal microorganisms in mice with formula powder rich in breast milk oligosaccharides:

At the phylum level, all groups shared high abundance of Firmicutes and Bacteroidetes. The AB-FMT-IF group also retained high abundance of Actinobacteria and Verrucomicrobia. The AB-FMT-2′-FL/IF group had a high abundance of Actinobacteria, and the AB-FMT-HM group maintained a high abundance of Verrucomicrobia (Fig. 1A). At the genus level, the AB-FMT-HM group mainly consists of Muribaculaceae , Akkermansia and Lachnospiraceae_NK4A136_group ; the AB-FMT-2'-FL/IF group has high abundance of Muribaculaceae , Lachnospiraceae_NK4A136_group and Blautia (Figure 1B) . In addition to this, the AB-FMT-2′-FL/IF group contained the highest number of bifidobacteria.

The gut microbiota biomarker categories under different treatments were analyzed using linear discriminant analysis effect size (LEfSe) based on linear discriminant analysis (LDA). The cladogram shows the distribution of dominant bacteria at each taxonomic level in the three groups from inside to outside (Fig. 2A). Figure 2B shows significantly different microbial communities between LDA>3 groups. We observed 41 dominant taxa (from class to partial species level) in different treatment groups. Notably, Enterobacter and Lachnospiraceae_UCG-006 were significantly enriched in the AB-FMT-IF group, accounting for 16% and 9% of the total intestinal flora composition, respectively (Figure 3A). However, the abundance of these two genera in the AB-FMT-HM group and AB-FMT-2'-FL/IF group was significantly lower than that in the AB-FMT-IF group (p < 0.05). Blautia and Olsenella were significantly enriched in the AB-FMT-2'-FL/IF group. The abundance of Blautia in the AB-FMT-2'-FL/IF group is close to 6%, which is significantly higher than the AB-FMT-IF group (p<0.05) and equivalent to the AB-FMT-HM group (p>0.05) (Figure 3B ).

It can be seen that 2'-FL can affect the composition of intestinal flora, and adding 2'-FL improves the gap between artificial feeding and breastfeeding. LEfSe analysis showed that the addition of 2'-FL/IF enriched a new functional genus with potential probiotic properties - Blautia , which maintain intestinal homeostasis and suppress inflammation by promoting the production of short-chain fatty acids. Olsenella , another iconic genus of the AB-FMT-2'-FL/IF group, is one of the oligosaccharide-degrading bacteria in the intestine. The most significant change in the intestinal flora after the addition of oligosaccharides was the increase in the abundance of Olsenella .

These results indicate that oligosaccharides and Olsenella reciprocally select. Adding 2′-FL to IF feed significantly increased the relative abundance of Bifidobacterium. Bifidobacteria have positive interactions with HMOs (especially 2′-FL) in the intestine. 2'-FL promotes the colonization and enrichment of Bifidobacterium in the infant intestine. Bifidobacteria regulate the composition of intestinal flora in early infancy. Meanwhile, Bifidobacteria are bacteria in the intestine that preferentially produce short-chain fatty acids.

Example 4

Regulation of intestinal short-chain fatty acids in mice with formula powder rich in human milk oligosaccharides:

The results showed that the AB-FMT-HM group had the highest total SCFA, acetic acid, propionic acid and butyric acid contents, and the AB-FMT-HM group had the total short-chain fatty acid SCFA content of 24.46 μmol/g, which was significantly higher than AB-FMT-IF. group (p<0.05, Figure 4A). The total content of SCFAs in the AB-FMT-2'-FL/IF group reached 81.28% of that in the AB-FMT-HM group, and there was no statistically significant difference compared with the AB-FMT-HM group (p>0.05). Acetate, propionate, and butyrate are macroscopic SCFA in the intestine, and compared with the AB-FMT-HM group, the macroscopic SCFA content in the AB-FMT-IF group was significantly reduced (p < 0.05). There was no significant difference in the acetate and propionate contents in the AB-FMT-2'-FL/IF group compared with the AB-FMT-HM group (p ＞ 0.05), but the butyrate content was significantly reduced (p ＜ 0.05, Figure 4B). Isobutyric acid, valeric acid and isovaleric acid are trace amounts of SCFA, and the valeric acid content in the AB-FMT-2'-FL/IF group and AB-FMT-IF group was significantly lower than that in the AB-FMT-HM group (p <0.05). There was no statistically significant difference in the contents of isobutyric acid and isovaleric acid among the three groups (p>0.05, Figure 4C). HMO formula feeding is similar to breastfeeding.

Example 5

The regulation of serum biochemical indicators and immune function in mice with formula powder rich in breast milk oligosaccharides:

Compared with the AB-FMT-IF group, the AST, CREA, and UA in the AB-FMT-2'-FL/IF group were significantly reduced, and ALP was significantly increased. Furthermore, the levels of these parameters in the AB-FMT-2′-FL/IF group were similar to those in the AB-FMT-HM group.

Table 3 Regulatory effects of formula powder rich in breast milk oligosaccharides on serum biochemistry

Cytokine levels (IL-2, IL-9, IL-10, and sIgA) were significantly different in the AB-FMT-IF group compared with the AB-FMT-HM group (Fig. 5). In contrast, there were no significant differences in these cytokines in the AB-FMT-2′-FL/IF group. This result may indicate that breast milk versus conventional formula affects immune index levels differently. Formulas supplemented with 2'-FL had serum immune levels similar to human milk.

Example 6

Compared with formula powder containing a 2'-FL/3'-SL mixture, the formula powder rich in 2'-FL proposed by the present invention exhibits enhanced effects in regulating short-chain fatty acid metabolism and regulating host immune function. There was no significant difference in the composition of intestinal microorganisms between formulas rich in 2'-FL and formulas containing a mixture of 2'-FL/3'-SL.

In order to measure whether 2'-FL can play an independent role in improving intestinal microbial composition, short-chain fatty acid metabolism and regulating host immune function, we used 2'-FL+3'-SL as a control to explore this issue. The intestinal composition of the AB-FMT-2'-FL group and the AB-FMT-2'-FL+3'-SL group are similar, and the main bacterial phyla and genera are the same (Figure 1 and Figure 3) , which shows that 2'-FL can independently improve the composition of intestinal microorganisms. The results of the intestinal short-chain fatty acid metabolism levels showed that compared with the formula powder without breast milk oligosaccharides, the AB-FMT-2'-FL group and the AB-FMT-2'-FL+3'-SL group had The metabolic level of short-chain fatty acids was improved, and the contents of acetic acid, propionic acid, and butyric acid were significantly increased (Figure 4). In particular, compared with the formula powder containing the 2'-FL/3'-SL mixture, the formula powder group rich in 2'-FL proposed by the present invention has a higher total short-chain fatty acid content, which is beneficial to infant health and immunity. Development is more beneficial. In addition, the content of several major short-chain fatty acids also increased, such as acetic acid, propionic acid and butyric acid. In addition, for the detection of immune indicators, the AB-FMT-2'-FL+3'-SL group played an overall similar immunomodulatory function as the AB-FMT-2'-FL group (Figure 5). Notably, the levels of IL-2, IL-9, and IL-10 in the AB-FMT-2'-FL group were closer to breast milk. These results indicate that 2'-FL can independently play an important role in improving intestinal microbial composition, short-chain fatty acid metabolism and regulating host immune function. At the same time, 2'-FL is also the most abundant oligosaccharide in breast milk and is the most critical link in improving infant formula. In terms of the preparation of 2'-FL, the existing technology is also the most complete, and the preparation of other types of oligosaccharides is not yet mass-produced. Therefore, the proposal of this formula will greatly improve the gap between conventional formula powder and breast milk, and at the same time, the feasibility is the highest.

The above are only the preferred embodiments of the present invention. It should be pointed out that those of ordinary skill in the art can make several improvements and modifications without departing from the principles of the present invention. These improvements and modifications can also be made. should be regarded as the protection scope of the present invention.

Claims (8)

1. A formula powder rich in breast milk oligosaccharides that improves the intestinal microbial composition of infants and young children and promotes the production of short-chain fatty acids, characterized in that it consists of the following raw materials by weight: breast milk oligosaccharides 2'-FL 80- 100 parts, 5000-7000 parts of fresh milk, 1000-2000 parts of desalted whey powder, 2-3 parts of DHA powder, 3-7 parts of ARA powder, 200-300 parts of OPO structural fat, 15-40 parts of flaxseed oil, coconut 50-80 parts of oil, 150-200 parts of sunflower oil, 20-40 parts of soy lecithin, 150-400 parts of lactose, 2-4 parts of compound minerals, 2-4 parts of compound vitamins, 1 compound mixed nutrient -2 servings; Each portion of the compound minerals contains: magnesium: 10.1-12.9 mg; iron: 2.1-4.4 mg; zinc: 1-3 mg; manganese: 65-85 μg; iodine: 47.8-89.5 μg; copper: 50-125 μg; Selenium: 3.5~7.0μg, chromium 0.3~0.8μg, molybdenum 0.6~2μg; Each serving of the compound vitamins contains: vitamin A: 100-150 μg RE; vitamin D: 2.0-3.5 μg; vitamin E: 2.5-6.0 mg; vitamin K1: 9-13 μg; vitamin B1: 130-180 μg; vitamin B2 : 300～450μg; Vitamin B6: 65～80μg; Vitamin B12: 0.2～1.2μg; Inositol: 8.5～13μg; Folic acid: 8～17μg; Pantothenic acid: 600～1800μg; Vitamin C: 15～32μg; Biotin: 3.5 ~5.6μg, lutein 28~50μg; Each serving of the compound mixed nutritional supplement contains: 11 to 23 mg of nucleotides, 45 to 56 mg of choline, 8.5 to 17.0 mg of taurine, and 2.5 to 6.0 mg of L-carnitine. 2. The formula powder rich in breast milk oligosaccharides according to claim 1, characterized in that: 90 parts of breast milk oligosaccharide 2'-FL, 6000 parts of fresh milk, 1500 parts of desalted whey powder, 2.5 parts of DHA powder, 5 parts of ARA powder, 250 parts of OPO complex fat, 26 parts of flaxseed oil, 65 parts of coconut oil, 180 parts of sunflower oil, 30 parts of soy lecithin, 250 parts of lactose, 3 parts of compound minerals, 3 parts of compound vitamins, 1 part of mixed nutritional supplement. 3. The formula powder rich in breast milk oligosaccharides according to any one of claims 1-2, which contains breast milk oligosaccharide 2'-FL14.2-3182.2mg/100g, and the protein of the infant formula powder The content is 1.46±0.07g/100mL, the fat content is 3.41±0.04 g/100mL, the lactose content is 7.03±0.02 g/100mL, and the total solid content is 13.00±0.00 g/100mL. 4. The application of the breast milk oligosaccharide-rich formula powder according to any one of claims 1 to 3 in the preparation of food for improving the intestinal microbial composition of infants and young children and promoting the production of short-chain fatty acids, characterized in that: The above-mentioned improvement of the intestinal microbial composition of infants and young children refers to the enrichment of Blautia and Olsenella . 5. The application of claim 4, wherein the short-chain fatty acids include acetic acid, propionic acid, and butyric acid. 6. Application of the breast milk oligosaccharide-rich formula powder according to any one of claims 1 to 3 in the preparation of products for regulating the level of anti-inflammatory cytokines, characterized in that regulating the level of anti-inflammatory cytokines refers to cytokines The levels of IL-2, IL-9, and IL-10 are close to those of human milk, and the level of IL-4 is lower than that of human milk. 7. Application of the breast milk oligosaccharide-rich formula powder in preparing food according to any one of claims 1 to 3, characterized in that the food can improve the intestinal microbial composition of infants and young children and enrich blautia and Olsenella. ; Promote the production of acetic acid, propionic acid, and butyric acid; regulate anti-inflammatory cytokines IL-2, IL-9, and IL-10. The levels are close to human milk, and the IL-4 level is lower than human milk. 8. The preparation method of formula powder rich in breast milk oligosaccharides according to claims 1 to 3, characterized in that the steps are as follows: Step 1: Raw milk is inspected, pre-treated, sterilized, cooled to 4°C and stored at <4°C; Step 2, Ingredients: Add breast milk oligosaccharides, desalted whey powder, ARA powder, DHA powder, lactose and complex vitamins, minerals, and nutrients into the ingredient tank, and finally add OPO structural fat, sunflower oil, coconut oil, and flax. oil, and the milk obtained is premixed at 60±5°C; Step 3: Homogenization: The premixed liquid is subjected to secondary homogenization at 60±5°C. The primary homogenization pressure is 10-20Mpa and the secondary homogenization pressure is 2-3Mpa. After homogenization, cool to below 6°C, keep the pH value of the material at 6.70-6.90, and store it in a temporary storage tank; Step 4, sterilization: Use pasteurization at a temperature >80°C. The optimal temperature is 86-92°C, 20-60S. Basis: This temperature combination helps to control the microorganisms of the product and can form some natural antioxidants to control the functional properties of the milk powder; Step five, concentration and drying: The sterilized milk is concentrated through a three-effect evaporator to a dry matter content of 45-55%; the concentrated liquid is dried through a spray drying tower, and the air inlet temperature is 186°C-215 ℃; dry exhaust temperature: 72-91 ℃. When the negative pressure of the drying tower is normal: -0.03 Mpa ~-0.58 Mpa, adjust the milk powder particles by adjusting the high-pressure pump pressure, nozzle size and agglomeration tube angle; Step six, fluidized bed cooling and screening: fluidized bed section I, II, and III temperature: 15-95°C; fluidized bed section IV temperature: 15-40°C. After cooling, sieve; Step seven, packaging and testing.