CN112868800A - Infant formula milk powder containing breast milk oligosaccharide for improving immunity and preparation method thereof - Google Patents
Infant formula milk powder containing breast milk oligosaccharide for improving immunity and preparation method thereof Download PDFInfo
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- CN112868800A CN112868800A CN202011369703.3A CN202011369703A CN112868800A CN 112868800 A CN112868800 A CN 112868800A CN 202011369703 A CN202011369703 A CN 202011369703A CN 112868800 A CN112868800 A CN 112868800A
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- bifidobacterium lactis
- breast milk
- infant formula
- cfu
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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Abstract
The invention mainly relates to infant formula Milk powder containing breast Milk oligosaccharide for improving immunity and a preparation method thereof, wherein the infant formula Milk powder contains Bifidobacterium lactis and Human Milk Oligosaccharides, and the breast Milk oligosaccharide comprises 2 ' -fucosyllactose, 2 ' -FL or 2-FL. The infant formula milk powder can effectively improve the gastrointestinal tract immunity.
Description
Technical Field
The invention mainly relates to infant formula Milk powder containing HMO (Human Milk Oligosaccharides) for improving immunity and a preparation method thereof, in particular to infant formula Milk powder containing HMOs (Human Milk Oligosaccharides) and probiotics, especially Bifidobacterium lactis (Bifidobacterium lactis), and a preparation method and application thereof.
Background
Over the last thousand years, medical literature has documented a high rate of morbidity and mortality in infants who are not breastfed. The breast milk not only provides the required nutrition for the infant, but also provides the guarantee for the intestinal development and the immunity improvement of the infant by the active ingredients in the breast milk. Breast-fed infants have a higher relative abundance of beneficial bacteria, particularly bifidobacteria and lactic bacteria, in the gut flora compared to formula-fed infants.
The breast milk is transferred by flora, and active ingredients such as breast milk oligosaccharide and cytokine in the breast milk are added to establish healthy intestinal flora for the newborn. The infant intakes 10 via breast milk every day7-108Individual bacteria, including lactic acid bacteria and bifidobacteria. These bacteria are directly transmitted through breast milkFor infants, part of the intestinal flora can be colonized in the intestinal tract of the infant, so that the establishment of the intestinal flora in early life is promoted. The establishment of the infant's intestinal flora has short-term, even lifelong effects on the development of its intestinal tract, as well as on the health and immune system.
Breast Milk Oligosaccharides (HMOs) belong to the third most abundant substances in breast Milk, except lactose and fat. The total content varies at various stages of lactation, and is about 12-14g/L in mature milk and about 20-24g/L in colostrum. Each breast milk oligosaccharide has a lactose at the reducing end, mostly with poly lactosamine as the structural backbone, and fucose, sialic acid, or both at the chain end. HMOs are present in individual differences in content and are associated with the lewis secretory component of the nursing mother. Since the raw material of infant formula is usually cow's milk, which usually contains no or very little such oligosaccharides, HMOs constitute a gap that infant formula is expected to approach the breast milk.
In the last 90 s of the century, HMO, 2-fucosyllactose (2' -FL), contained in most breast milk, was found to be effective in reducing the toxicity of stable toxins in escherichia coli; by 2003, the oligosaccharides were reported to inhibit the attachment and infection of jejunum flexuosum. Subsequently, three major functions of breast milk oligosaccharides were gradually reported and discovered: (1) inhibiting attachment and infection of specific pathogens; (2) as a prebiotic, the growth of bacteria in the intestinal tract symbiotic system is promoted; (3) directly slow down the inflammatory reaction of mucosa under toxic stimulation. The first clinical intervention trial with 2' -FL demonstrated that the addition of this specific ingredient to a low calorie formula was not only safe but also allowed formula-fed infants to grow at a rate comparable to breast-fed infants. 2' -FL is also used as a nutritional supplement for adults, to alleviate irritable bowel syndrome or inflammatory bowel disease, or as a prebiotic to maintain intestinal flora balance.
The intestinal flora is an important component of a human intestinal microecosystem and has important effects on human health, such as supplying essential nutrients, generating vitamin K, assisting a digestion process and promoting angiogenesis and intestinal nerve. Prebiotics and probiotics are considered as micro-ecological management tools for improving the health of the body, altering, regulating and recombining the already existing intestinal flora.
Currently, in the field of infant formula powder, supplementary food and nutritional supplements, solutions for alleviating infant intestinal discomfort and improving autoimmune ability are needed. Meanwhile, in the fields of children, teenagers and adults over 3 years old, the balance of intestinal flora needs to be maintained, and the immunity is regulated.
Disclosure of Invention
One object of the present invention is to provide a maternal-emulsified infant formula.
The invention also aims to provide a preparation method of the maternal emulsified infant formula milk powder.
The invention also aims to provide application of the maternal emulsified infant formula.
The inventor of the present invention finds that the combination of Bifidobacterium lactis (Bifidobacterium lactis) and breast milk oligosaccharides has a synergistic effect on improving the gastrointestinal tract immunity.
Thus, in one aspect, the present invention provides a maternal emulsified infant formula comprising Bifidobacterium lactis (Bifidobacterium lactis) and breast milk oligosaccharides.
According to a particular embodiment of the invention, the Bifidobacterium lactis comprises Bifidobacterium lactis (Bifidobacterium lactis) strain HN019 and/or Bifidobacterium lactis (Bifidobacterium lactis) with the accession number CGMCC No.15650 in the milk formula for a maternal emulsified infant or child.
Bifidobacterium lactis (Bifidobacterium lactis) HN019 is a commercial strain available from Dupont Danisco.
The bifidobacterium lactis with the preservation number of CGMCC No.15650 is also named as bifidobacterium lactis BL-99. The strain has gastric acid resistance, and the survival rate of viable bacteria is more than 62% when the strain is treated in gastric acid liquid with pH of 2.5 for 30min and more than 61% when the strain is treated for 2 hours. The bifidobacterium lactis BL-99 provided by the invention also has intestinal juice resistance, and the survival rate of viable bacteria is more than 70% after being treated in small intestinal juice with pH of 6.8 for 2 hours. Mouse experiments show that the strain has no oral acute toxicity, no antibiotic tolerance and safety and can be used for food processing. The strain has been preserved in China general microbiological culture Collection center (CGMCC) 26.04.2018 (address: No. 3 Xilu-Beijing institute of microbiology, institute of China academy of sciences, North Cheng-Yang district, Beijing city), and is named after classification: bifidobacterium lactis (Bifidobacterium lactis); the preservation number is CGMCC No. 15650.
According to a particular embodiment of the invention, in the composition of the invention, the breast milk oligosaccharides comprise one or more of 2 '-fucosyllactose, 3' -fucosyllactose, lacto-N-tetraose, 3 '-sialyllactose, 6' -sialyllactose.
According to a particular embodiment of the invention, the breast milk oligosaccharides comprise 2 '-fucosyllactose, 3' -fucosyllactose, lacto-N-tetraose, 3 '-sialyllactose, 6' -sialyllactose in a weight ratio of (0-10): (4-8): (3-6): (1-4): 0-1).
According to a particular embodiment of the invention, the composition of the invention comprises the human milk oligosaccharides 2 '-fucosyllactose, 3' -fucosyllactose, lacto-N-tetraose, 3 '-sialyllactose, 6' -sialyllactose in a weight percentage (0-53%) (21% -44%) (16% -32%) (5% -22%) (0-5%). The weight percentage is based on the total amount of the breast milk oligosaccharide as 100%.
According to a specific embodiment of the present invention, the breast milk infant formula of the present invention may be an infant formula or an infant formula.
According to some preferred embodiments of the present invention, the bifidobacterium lactis is added in an amount of 1 × 10 in the maternal emulsion infant formula of the present invention3CFU/g～1×1012CFU/g, preferably 1X 106CFU/g～1×1010CFU/g。
According to some preferred embodiments of the present invention, the breast milk oligosaccharide is applied in an amount of 0.5% to 1.5% in the maternal emulsified infant formula according to the present invention.
According to a specific embodiment of the present invention, the breast-emulsified infant formula of the present invention may further comprise conventional components of infant formula in addition to the lactobacillus and breast milk oligosaccharides.
According to some preferred embodiments of the present invention, the raw materials of the breast milk-based infant formula of the present invention include, in addition to breast milk oligosaccharides and bifidobacterium lactis, 1000 parts by weight of the breast milk-based infant formula:
890-3800 parts of raw milk, 0-480 parts of lactose, 0-540 parts of desalted whey powder, 0-80 parts of whey protein powder WPC 80%, 0-120 parts of whey protein powder WPC 34%, 0-170 parts of structural oil OPO0, 0-150 parts of high-oleic acid sunflower seed oil, 0-50 parts of corn oil, 0-50 parts of low erucic acid rapeseed oil, 0-80 parts of soybean oil, 0-23 parts of beta-casein, 1-2.5 parts of soybean lecithin, 0-30 parts of fructo-oligosaccharide powder, 0-90 parts of galacto-oligosaccharide syrup, 1-5 parts of compound vitamin, 0-3 parts of choline chloride, 0-2 parts of mineral substance I and 1-9 parts of mineral substance II; wherein, the first mineral comprises copper, iron and iodine elements, and the second mineral comprises calcium and phosphorus elements;
one or more of the following components can also be optionally included: 0.20-2.04 parts of inositol, 0-0.65 part of taurine, 0.06-0.5 part of L-carnitine, 3-18 parts of DHA, and 3-18 parts of ARA.
In the formula, the protein and fat of raw milk can be replaced by whole milk powder and/or skim milk powder; the whey protein powder WPC80 and WPC34 can be partially replaced by alpha-lactalbumin.
The compound vitamins and various mineral substances in the formula can adopt a compound nutrient composition of nutrient components meeting national standards, different addition amounts are used according to different formulas, and the specific addition mode can be carried out according to the conventional operation in the field. Preferably, if the compound nutrient is added according to needs, any one or any combination of the following compound nutrient components can be selectively adopted (per gram content; the amount of each index is calculated according to the middle value of the addition range; the condition that all the index contents are simultaneously maximum does not exist basically):
vitamin A: 1300-4000 mu gRE; vitamin D: 24-60 mu g; vitamin E: 13-41 mg of alpha-TE
Vitamin K1: 200-550 μ g; vitamin B1: 2600-6500 mu g; vitamin B2：600～3000μg
Vitamin B6: 1200-4000 μ g; vitamin B12: 2-14.0 μ g; nicotinamide: 12000-30000. mu.g
Folic acid: 300-653 mu g; pantothenic acid: 8750-16230 μ g; biotin: 56-150 mu g; sodium: 30 to 400mg
Potassium: 63-400 mg; copper: 2200-5540 μ g; magnesium: 133-400 mg; iron: 23-95 mg; zinc: 25-52 mg
Calcium: 110-300 mg; phosphorus: 75-200 mg; iodine: 200-1592 μ g.
According to some preferred embodiments of the present invention, the milk powder for infant and mom formula of the present invention further comprises bifidobacterium animalis added in an amount of 2 × 106CFU/g～2×1012CFU/g, preferably 2X 106CFU/g～2×1010CFU/g。
On the other hand, the invention also provides a method for preparing the maternal emulsified infant formula milk powder, which adopts a wet method or dry method production process to mix the breast milk oligosaccharide and the bifidobacterium lactis with other raw materials in the formula to prepare the maternal emulsified infant formula milk powder.
Specifically, the wet process generally includes: preparing materials, wet method (HMO and probiotics), homogenizing, concentrating and sterilizing, spray drying and obtaining the finished product.
Dry production processes typically include: preparing materials, preheating, homogenizing, concentrating and sterilizing, spray drying, dry mixing (HMO and probiotics), and obtaining a finished product.
On the other hand, the invention also provides application of the maternal emulsified infant formula milk powder in serving as food with the effect of improving gastrointestinal tract immunity.
According to a specific embodiment of the present invention, the use of the present maternal emulsified infant formula as a food product with the efficacy of increasing gastrointestinal immunity, said improving gastrointestinal immunity comprising: resist pathogenic bacteria invasion in the intestinal system, and/or maintain intestinal shielding function.
According to a specific embodiment of the present invention, the use of the present maternal emulsified infant formula as a food product with the efficacy of increasing gastrointestinal immunity, said improving gastrointestinal immunity comprising: reduce the release of inflammatory factors IL-8 and/or IP-10 from intestinal cells.
The breast milk oligosaccharide, especially 2 '-fucosyllactose (2' -FL) and probiotic bacteria, especially bifidobacterium lactis contained in the breast milk-containing infant formula milk powder can regulate the immunity of infant intestinal tracts, resist the invasion of external pathogenic bacteria or play a synergistic role in infants and adults over 3 years old; the effects of regulating immunity and resisting pathogen invasion are verified by an anti-adhesion test, an intestinal barrier integrity test, an inflammatory factor release test and a test of the influence of a tested substance on the EPEC survival rate of pathogenic bacteria.
Drawings
FIG. 1 shows the effect of human milk oligosaccharide 2' -FL and human milk oligosaccharide mixture on the survival of the tested pathogenic bacteria EPEC.
FIG. 2 shows the effect of Bifidobacterium lactis HN019 and BL-99 strains on the survival rate of the tested pathogenic bacteria EPEC.
Figure 3 shows the effect of bifidobacterium lactis HN019 in combination with breast milk oligosaccharide 2' -FL or in combination with a breast milk oligosaccharide mixture on the survival rate of the test pathogen EPEC.
Figure 4 shows the effect of bifidobacterium lactis BL-99 in combination with the breast milk oligosaccharide 2' -FL or in combination with the breast milk oligosaccharide mixture on the survival of the tested pathogen EPEC.
FIG. 5A shows Bifidobacterium lactis HN019 (10)8) The result of an adhesion experiment of the combination of the composition and breast milk oligosaccharide 2' -FL (5g/L) on pathogenic bacteria EPEC acting on intestinal tract cells Caco-2; FIG. 5B shows 106The combination of bifidobacterium lactis HN019 and 2g/L breast milk oligosaccharide 2' -FL in concentration has an effect on the survival rate of the tested pathogenic bacteria EPEC.
FIG. 6A shows milk bifidobacteriaBacillus BL-99 (10)8) The result of an adhesion experiment of the combination of the composition and breast milk oligosaccharide 2' -FL (5g/L) on pathogenic bacteria EPEC acting on intestinal tract cells Caco-2; FIG. 6B shows Bifidobacterium lactis BL-99 (10) in another batch of experiments8) Results of experiments with the composition formed with 2' -FL (5g/L) for inhibiting the adherence of E.coli EPEC to Caco-2 cells.
FIG. 7A shows Bifidobacterium lactis HN019 (10)8) Effect on intestinal barrier in combination with breast milk oligosaccharide 2' -FL (5 g/L); FIG. 7B shows 106Effect of bifidobacterium lactis HN019 in concentration in combination with different concentrations of breast milk oligosaccharide 2' -FL on transmembrane resistance TEER under ETEC challenge conditions.
FIG. 8 shows 106Effect of Bifidobacterium lactis BL-99 in combination with 5g/L of breast milk oligosaccharide 2' -FL on transmembrane resistance TEER under ETEC challenge conditions.
FIG. 9 shows the effect of Bifidobacterium lactis HN019 in combination with breast milk oligosaccharide 2' -FL on secretion of the inflammatory factor IL-8 by intestinal cells in the absence of E.coli coculture.
FIG. 10 shows the effect of Bifidobacterium lactis HN019 in combination with breast milk oligosaccharide 2' -FL on secretion of inflammatory factor IP-10 by intestinal cells in the absence of E.coli coculture.
FIG. 11 shows the effect of Bifidobacterium lactis HN019 in combination with breast milk oligosaccharide 2' -FL on secretion of the inflammatory factor IL-8 by intestinal cells when cocultured with E.coli.
FIG. 12 shows the effect of Bifidobacterium lactis HN019 in combination with breast milk oligosaccharide 2' -FL on secretion of inflammatory factor IP-10 by intestinal cells when cocultured with E.coli.
FIG. 13 shows 106The composition of bifidobacterium lactis HN019 with concentration and breast milk oligosaccharide 2' -FL with different concentrations has the influence on the release of an inflammatory factor IL-8 by intestinal cells Caco-2 under the condition of pathogen ETEC invasion.
FIG. 14A shows Bifidobacterium lactis HN019 (10)8) The adhesion experiment result of the combination of the mixture and the breast milk oligosaccharide mixture A on the pathogenic bacteria EPEC acting on the intestinal tract cells Caco-2; FIG. 14B shows that different concentrations of Bifidobacterium lactis HN019 mixed with different ratios of HMO are effective in inhibiting large intestine rodsExperimental results for adherence of bacterial EPEC to Caco-2 cells.
FIG. 15A shows Bifidobacterium lactis BL-99 (10)8) The result of the adhesion experiment of the combination of the mixture and the breast milk oligosaccharide mixture B on the pathogenic bacteria EPEC acting on the intestinal tract cells Caco-2; fig. 15B shows the results of experiments with compositions of different concentrations of bifidobacterium lactis BL-99 and different ratios of HMO mixtures for inhibiting the adhesion of e.coli EPEC to Caco-2 cells.
FIG. 16A shows Bifidobacterium lactis HN019 (10)8) Effect on intestinal barrier in combination with breast milk oligosaccharide mixture a; figure 16B shows probiotic bacteria HN019 alone (10)8) Effect of HMO compositions A, B and F in different ratios on transmembrane resistance TEER in case of exposure to e.coli ETEC H10407; figure 16C shows probiotic HN019 alone (10)6) Effect of HMO composition a on transmembrane resistance TEER in case of exposure to e.coli ETEC H10407.
FIG. 17 shows probiotic BL-99 alone (10)8) Effect of HMO compositions A, B and F in varying proportions on transmembrane resistance TEER upon Exposure to E.coli ETEC H10407
FIGS. 18A and 18B show the effect of Bifidobacterium lactis HN019 in combination with a mixture of breast milk oligosaccharides on secretion of inflammatory factors IL-8 and IP-10 by intestinal cells in the absence of E.coli coculture.
FIGS. 19A and 19B show the effect of Bifidobacterium lactis HN019 in combination with a mixture of breast milk oligosaccharides on the secretion of inflammatory factors IL-8 and IP-10 by intestinal cells when cocultured with E.coli.
Microbial preservation of the patent procedure:
bifidobacterium lactis BL-99 of the present invention:
the preservation date is as follows: 26/04/2018;
the preservation unit: china general microbiological culture Collection center (CGMCC);
the address of the depository: xilu No.1 Hospital No. 3, the institute of microbiology, China academy of sciences, Beijing, Chaoyang
The preservation number is: CGMCC No. 15650;
and (3) classification and naming: bifidobacterium lactis (Bifidobacterium lactis).
Detailed Description
For a more clear understanding of the technical features, objects and advantages of the present invention, reference is now made to the following detailed description of the embodiments of the present invention taken in conjunction with the accompanying drawings, which are included to illustrate and not to limit the scope of the present invention. Unless specifically defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the relevant art.
The inventor proves that the probiotic composition has a synergistic effect in the aspect of regulating the gastrointestinal tract immunity through specific experiments.
The experimental methods and test substance cases used in the examples and the control are as follows:
1. preparation of the experiment
1.1 media preparation and storage and preparation of prebiotics tested
The medium containing prebiotics and probiotics was freshly prepared in a sterile environment on the day of each experiment and pre-warmed to 37 ℃. The prebiotics/HMOs tested were stored in a dry, dark room temperature environment. The concentration used in the experiment was 5 g/L.
1.2 probiotic culture, growth curve plotting and activity identification
The probiotic powder was sent to the laboratory in a freeze-dried state prior to the experiment. Probiotics were inoculated onto MRS-agar plates and individual populations of strains were taken for 16S rDNA identification and used to prepare glycerol stocks (stored at-80 ℃). Prior to each experiment, the probiotic was removed from the glycerol stock and inoculated on MRS plates at 37 ℃, harvested at rest, and rinsed with MEM medium prior to the experiment. Probiotic activity and cell number were measured with a fluorescence activated cell sorting system prior to probiotic testing. The probiotic concentration used in the experiment was 1X 108CFU/mL. Bifidobacterium lactis was cultured at 37 ℃ under anaerobic conditions and growth curves were drawn before the experiment. In harvestingTo the probiotic raw material and before all experiments were started, the activity of the probiotic strains was tested with a flow cytometer. 16S sequencing was used to determine strain identity. Before testing of each experiment of the probiotics, the activity and the cell number of the probiotics are measured by a fluorescence activated cell sorting system.
1.2.1 Bifidobacterium lactis BL-99
The bifidobacterium lactis BL-99 is separated from the intestinal tract of the infant. The strain has been preserved in China general microbiological culture Collection center (CGMCC) 26.04.2018 (address: No. 3 Xilu-Beijing institute of microbiology, institute of China academy of sciences, North Cheng-Yang district, Beijing city), and is named after classification: bifidobacterium lactis (Bifidobacterium lactis); the preservation number is CGMCC No. 15650.
1.2.1.1 taxonomic characterization of Bifidobacterium lactis BL-99
The results of the physical and chemical tests are as follows:
1.2.1.2 tolerance of Bifidobacterium lactis BL-99 to artificial gastric juice and intestinal juice
Bifidobacteria are genera that are generally not acid-fast. In this example, the tolerance of bifidobacterium lactis BL-99 of the present invention to artificial gastric juice and intestinal juice was tested, and bifidobacterium lactis which had been recognized in the art as having excellent acid resistance and survived through the gastrointestinal tract
For comparison.
The test method comprises the following steps: culturing Bifidobacterium lactis BL-99 strain in MRS liquid culture medium at 37 deg.C for 16 hr, centrifuging at 4 deg.C and 2500rpm for 10min, and collecting thallus.
Respectively culturing the strains to be tested in artificial gastric juice and artificial small intestine juice, processing at 37 ℃ for 0, 30min and 2h, and then performing viable count analysis to evaluate the acid resistance and intestinal juice resistance of the strains according to the survival rate. Survival rate (viable cell count after treatment/viable cell count at time 0) × 100%.
The survival rate detection result of the bacterial strain in artificial gastric acid (pH2.5) is shown in Table 1, the survival rate of the viable bacteria is 7.04% when BB-12 is treated in the artificial gastric acid (pH2.5) for 30min, and the survival rate of the viable bacteria is only 1.64% after 2 hours of treatment; the survival rate of the live bacteria of the bifidobacterium lactis BL-99 is 62.60 percent when the bifidobacterium lactis BL-99 is treated in artificial gastric acid (pH2.5) for 30min, and the survival rate of the live bacteria is 61.83 percent when the bifidobacterium lactis BL-99 is treated for 2 hours. The bifidobacterium lactis BL-99 disclosed by the invention has excellent gastric acid resistance and can smoothly pass through the stomach to reach the intestinal tract to play a probiotic role.
TABLE 1 survival rate of the strains in artificial gastric acid (pH2.5)
The survival rate of the strain in the artificial small intestine solution (pH6.8) is tested and shown in Table 2. The data show that the viable bacteria survival rate of BB-12 in artificial small intestine solution (pH6.8) for 2 hours is only 28.95%; the viable bacteria survival rate of the bifidobacterium lactis BL-99 is 70.23 percent when the bifidobacterium lactis BL-99 is treated in artificial gastric acid (pH2.5) for 2 hours. The bifidobacterium lactis BL-99 disclosed by the invention has excellent intestinal juice resistance and can survive and colonize in intestinal tracts.
TABLE 2 survival rate of the strains in artificial intestinal juice (pH6.8)
1.2.1.3 toxicity test and safety detection of Bifidobacterium lactis BL-99
Inoculating the bifidobacterium lactis BL-99 of the invention into a BBL liquid culture medium, carrying out anaerobic culture for 48 +/-2 hours at 36 +/-1 ℃, and counting the viable count of the bifidobacterium lactis BL-99 in the culture solution to be 3.7 multiplied by 108cfu/mL, stock solutions and 5-fold concentrates of the cultures were continuously gavaged to 20.0mL/kg BW for 3 days and observed for 7 days. The experiment was performed with a control group of 5-fold concentrated solution and a stock solution of the medium. The test result shows that: compared with the respective control group, the BBL culture stock solution and the 5-fold concentrated solution group of the bifidobacterium lactis BL-99 have no statistical significance (p is more than 0.05) on the weight gain of the mice, and meanwhile, the BBL culture stock solution and the 5-fold concentrated solution group of the bifidobacterium lactis BL-99 have no observationThe test mice were observed to have a toxic response or died.
The antibiotic sensitivity of the bifidobacterium lactis BL-99 is evaluated by adopting an SN/T1944-2007 method of determination of bacterial resistance in animals and products thereof. The evaluation results show that the bifidobacterium lactis BL-99 is sensitive to Ampicillin Ampicillin, penicillin G Penicillin G, Erythromycin Erythromycin, Chloramphenicol Chloramphenicol, Clindamycin Clindamycin, Vancomycin Vancomycin, Tetracycline and the like. Meets the requirements of European Food Safety Authority (European Food Safety Authority) on the evaluation specification of the resistance of the edible bacteria. The bifidobacterium lactis BL-99 does not contain exogenous antibiotic resistance genes and is safe to eat.
1.2.2 Bifidobacterium lactis HN019
The HN019 strain was supplied by Dupont Danisco.
1.3 formulation of different combinations of prebiotics and probiotics
The concentration of prebiotics tested in the combination was 5 g/L; the number of probiotics tested is 1 × 108CFU/mL。
The first round of testing: five combined prebiotics 2' -FL:3-FL: LNT:3-SL:6-SL ═ 10:4:3:1
And (3) testing in a second round: the proportion and percentage of the five combined prebiotics are shown in the following tables 3 and 4.
TABLE 3
| Ratio of | 2’-FL | 3-FL | LNT | 3-SL | 6- |
| Composition A | |||||
| 10 | 4 | 3 | 1 | 1 | |
| |
10 | 4 | 3 | 2 | 0 |
| Composition C | 9 | 6 | 3 | 2 | 0 |
| |
0 | 8 | 6 | 4 | 0 |
| Composition F | 12.5 | 5.75 | 4.25 | 1.5 | 1 |
TABLE 4
| Percent by weight% | 2’-FL | 3-FL | LNT | 3-SL | 6-SL |
| Composition A | 53 | 21 | 16 | 5 | 5 |
| Composition B | 53 | 21 | 16 | 10 | 0 |
| Composition C | 45 | 30 | 15 | 10 | 0 |
| |
0 | 44 | 32 | 22 | 0 |
| |
50 | 23 | 17 | 6 | 4 |
1.4Caco-2 cell culture
Human colon tumor cell line (Caco-2) was obtained from DSMZ (Bilelix, Germany) and cultured in the presence of 5% CO2Culturing at 37 deg.C under certain humidity. Caco-2 cells from passage 40-44 were used for the experiments. To MEM medium was added 20% (v/v) Fetal Bovine Serum (FBS), 1% nonessential amino acids, 1% Glutamax, 1% sodium pyruvate, with or without 1% penicillin-streptomycin solution, and 50g/mL gentamicin (all available from Invitrogen corporation, Netherlands Brandy). Cells were grown to 80% abundance in T75 flasks and harvested by trypsinization.
1.5 cultivation of pathogenic bacteria ETEC and EPEC
ETEC cell line H10407(ATCC35401) was cultured in BHI-B medium (Merck, N.Y.). After overnight incubation at 37 ℃ under anaerobic conditions, the pathogen was re-incubated prior to infection to reach mid-log phase. Cells were harvested by centrifugation, washed and resuspended in PBS prior to the experiment.
Strain EPEC serotype O119 was purchased from DSMZ under freeze-dried conditions (DSM 8699). The strains were cultured in BHI-B medium (Merck, N.Y. USA). After overnight incubation at 37 ℃ under anaerobic conditions, the pathogen was re-incubated prior to infection to reach mid-log phase. Cells were harvested by centrifugation, washed and resuspended in PBS prior to the experiment.
1.6 data analysis
If possible, three replicates (sometimes six replicates) were used to perform the statistical analysis of each individual test. Anti-adhesion data were transformed with log 10. Statistical analysis was performed using one-way ANOVA for anti-adhesion data and epidermal signal transmission data after log10 transformation. The Dunnett's posthoc test was used to identify statistical differences from negative controls or with E.coli stimulation. Statistical differences between the negative control and the test groups at each time point in the transmembrane resistance TEER test were analyzed using the two-way ANOVA and Dunnett's posthoc test. One-way ANOVA statistical analysis was performed in the testing of the inflammatory factors IL-8 and IP-10, and significance analysis was performed using the Dunnett's posthoc test. Significant differences are indicated by asterisks: represents p <0.05, represents p <0.01, represents p <0.001, represents p < 0.0001. P <0.05 was considered to be significantly different. The groups marked with asterisks have significant statistical differences with the groups not marked with asterisks, and the difference degree is different according to the number of asterisks. Since Dunnett's posthoc test used ANOVA MSResidual as a pooled assessment of differences and modified significance values to adjust the number of comparisons, the same results may be significant in one graph and not in the other.
2. Specific experimental procedures
2.1 anti-adhesion test
Caco-2 cells were cultured in 24-well plates. On the day of the assay, Caco-2 cells were washed with pre-warmed PBS. The test substances were added to Caco-2 cells in triplicate. Cells were cultured with the test substance for 1 hour. Pathogenic E.coli was then added, at a multiple of infection (MOI) 50: 1 addition (final concentration 10)7CFU/mL), and the test substance were incubated at 37 ℃ for 1 hour. As a negative control, Caco-2 cells were cultured in medium with pathogenic bacteria only. 1mM zinc oxide (ZnO) was used as a positive control, as it was reported to reduce pathogen adsorption. In cultureThereafter, the Caco-2 cells were washed and lysed, and then the pathogen was inoculated on agar. After overnight incubation on agar plates at 37 ℃, CFU colonies of bacteria were counted to measure pathogen adsorption. The number of growing E.coli colonies was counted and recorded as CFU/mL. In parallel to the anti-adhesion test, Escherichia coli (final concentration of) 107CFU/mL was added to 1mL of the five combinations tested and co-incubated at 37 ℃ for 1 hour to measure activity. After incubation, E.coli was harvested from each sample by centrifugation, resuspended in PBS, and plated on agar plates. After overnight incubation on agar plates at 37 ℃, CFU colonies of bacteria were counted to measure pathogen adsorption. The number of growing E.coli colonies was counted and recorded as CFU/mL.
2.2 intestinal Barrier integrity test
The ideal small intestinal epithelial barrier function is a prerequisite to protect the host from pathogenic invasion and/or pathogenic toxins. In this study, barrier integrity in vitro was demonstrated by measuring the transepidermal electrical resistance (TEER) of the intestinal cell layer. Food ingredients may have the function of protecting the intestinal barrier function from decreasing after infection (reducing the decrease in TEER after infection). To study the effect of prebiotics and probiotics on infection, the TEER was measured before and after infection with e.
Caco-2 cells were seeded into Transwell polycarbonate cell culture inserts with an average pore size of 0.4um and an area of 0.33cm2Until complete differentiation (± 1000 Ω). Trans-epithelial electrical resistance (TEER) was measured with an EVOM2 epidermal voltmeter purchased from a world precision instrument to measure barrier integrity.
On the day of testing, cells were washed and cultured for 1 hour at 37 ℃ in medium without antibiotics and serum, but containing the test substance. Immediately thereafter, E.coli was added to the test substance (the infection magnification MOI was 200:1) and cultured for 6 hours. TEER was measured 1 hour, 2 hours, 3 hours, 4 hours and 6 hours after exposure of the test substance and before addition of the pathogen before the start of the experiment (t ═ 1), and 1 hour, 2 hours, 3 hours, 4 hours and 6 hours after pathogen exposure, respectively. The TEER values under the individual conditions after exposure to a pathogen correlate with their TEER values at t ═ 0 and are expressed as Δ TEER (Ω. Cm 2). Negative controls (addition of E.coli only) and positive controls not exposed to pathogenic bacteria or test substances were also included in the experimental group. All conditions were assayed in triplicate and some controls were assayed in 6 replicates.
2.3 inflammatory factor Release assay
Prebiotics and probiotics can have immunomodulatory (promoting or anti-inflammatory) effects, can increase resistance to infection or promote gut health. The immunomodulatory effects of prebiotic probiotics can be measured by measuring cytokine/chemokine production by small intestine epithelial cells in the presence or absence of a pro-inflammatory stimulus. The effect of prebiotics and probiotics on chemokine/cytokine production can be screened by stimulating Caco-2 cells with E.coli strains and measuring the production of IL-8 and IP-10 in the supernatant. IL-8 is important for an urgent autoimmune response, which can lead to the aggregation of neutrophils. IP-10 is important in the secondary response of immunity. It attracts monocytes and macrophages, also including Th1 cells, which play an important role in the clearance of infection. Pro-inflammatory prebiotics and probiotics may increase the production of IL-8 and/or IP-10, while anti-inflammatory prebiotics and probiotics may decrease the production of IL-8 and/or IP-10.
Caco-2 cells were cultured in 96-well plates to appropriate abundance. At the beginning of the experiment, cells were washed once with medium without antibiotics. The monolayer cells were co-cultured with the test substance at 37 ℃ for 1 hour in a medium containing no antibiotic, and this was repeated three times. Coli stimulating cells (MOI 200:1) were added. After 1 hour incubation, the monolayer cells were co-cultured with the pathogens and rinsed and incubated overnight with medium containing the test substance and 50g/mL gentamicin. As a blank control, only the culture broth was used without stimulation with E.coli. Culture broth stimulated with E.coli but without test substance was used as a control for E.coli response. In addition, as a control for Caco-2 cell response, cells were stimulated with a mixture of cultures containing Rec TNF α (10ng/mL) and Rec IFN γ (5ng/mL), both purchased from R & D systems of Abindion, UK. Supernatants were collected after 24 hours of stimulation and stored at-20 ℃. IL-8 and IP-10 were tested using the Bio-Plex kit (BioRad, Calif., USA) according to the manufacturer's instructions.
3. Test for influence of test substance on EPEC survival rate of pathogenic bacteria
To verify whether the reduction in pathogenic adsorption is associated with pathogenic activity, pathogenic activity was also tested after culturing prebiotics and probiotics. As shown in fig. 1-4, similarly to other tested probiotics or prebiotics, the survival rate of escherichia coli EPEC 0119 bacteria is not significantly affected after the test substance HN019 or 2' -FL is added or the combination of the two is added; BL-99 or 2' -FL, like other tested probiotics or prebiotics, did not significantly affect the survival rate of EPEC 0119 bacteria; and the combination of both slightly reduced the survival rate of the EPEC 0119 bacterium. After the tested substance HN019 or HMO mixture is added, the survival rate of the escherichia coli EPEC 0119 bacterium is not obviously influenced; the survival rate of the escherichia coli is slightly reduced by adding the composition B; after the test substance BL-99 or the HMO mixture or the combination of the two is added, the survival rate of the Escherichia coli EPEC 0119 bacteria is not influenced significantly.
Example 1: effect of Bifidobacterium lactis and breast milk oligosaccharide 2' -FL on gastrointestinal tract immunity
1. Experimental result of intestinal adhesion experiment of combination of bifidobacterium lactis HN019 and breast milk oligosaccharide 2' -FL on pathogenic bacteria EPEC
The preparation steps before the experiment and the specific experimental methods are described in the preceding paragraphs. Bifidobacterium lactis HN019 has a normal growth curve. The protective effect of probiotics and prebiotic compositions to prevent pathogenic bacteria from adsorbing to small intestine epithelial cells was studied by the common diarrheagenic strain EPEC O119.
As shown in the result of FIG. 5A, the adhesion of the single breast milk oligosaccharide 2' -FL (5g/L) to the pathogenic bacteria Escherichia coli O119 to the intestinal tract cells Caco-2 is not significantly different from that of the negative control, while the positive control zinc oxide can significantly reduce the adsorption of the pathogenic bacteria to the intestinal tract cells (p)<0.0001). Probiotics HN019 alone (10)8) The adhesion effect of the pathogenic bacterium Escherichia coli O119 on intestinal tract cells Caco-2 is not significantly different from that of a negative control.However, when prebiotics 2' -FL and probiotics are used as the test substance of the treatment group, the prebiotics and the probiotics significantly reduce the adsorption of the pathogenic bacteria EPEC 0119 to intestinal cells (p)<0.01). Showing a synergistic effect when the two are formed into a composition.
FIG. 5B shows 106The combination of bifidobacterium lactis HN019 and 2g/L breast milk oligosaccharide 2' -FL in concentration has an influence on the survival rate of the tested pathogenic bacteria EPEC, and the data of experimental results (mean value +/-standard error, repeated three times of measurement) are shown in Table 5. 10 in comparison with the negative control group6The probiotic group of (A) significantly reduces the adherence of EPEC to the intestinal cell surface (P)<0.05), and 106The composition of probiotic bacteria with 2-FL also significantly reduces the adhesion of EPEC to the intestinal cell surface (P)<0.05)。
TABLE 5
2. Experimental result of intestinal adhesion experiment of combination of bifidobacterium lactis BL-99 and breast milk oligosaccharide 2' -FL on pathogenic bacteria EPEC
The preparation steps before the experiment and the specific experimental methods are described in the preceding paragraphs. The tested bifidobacterium lactis BL-99 has a normal growth curve. The protective effect of probiotics and prebiotic compositions to prevent pathogenic bacteria from adsorbing to small intestine epithelial cells was investigated by common diarrheagenic strains (EPEC O119).
As shown in the result of FIG. 6A, the adhesion of the single breast milk oligosaccharide 2' -FL (5g/L) to the pathogenic bacteria Escherichia coli O119 to the intestinal tract cells Caco-2 is not significantly different from that of the negative control, while the positive control zinc oxide can significantly reduce the adsorption of the pathogenic bacteria to the intestinal tract cells (p)<0.0001). Probiotics BL-99 alone (10)8) The adhesion effect of the pathogenic bacterium Escherichia coli O119 on intestinal tract cells Caco-2 is not significantly different from that of a negative control. However, when prebiotics 2' -FL and probiotics are used as the test substance of the treatment group, the prebiotics and the probiotics significantly reduce the adsorption of the pathogenic bacteria EPEC 0119 to intestinal cells (p)<0.001). Showing a synergistic effect when the two are formed into a composition.
FIG. 6B shows anotherOne batch of Bifidobacterium lactis BL-99 (10) in the experiment8) The results of experiments with the composition formed with 2' -FL (5g/L) for inhibiting the adherence of E.coli EPEC to Caco-2 cells are shown in Table 6 (mean. + -. standard error, three replicates). The 2-FL (5g/L) group significantly reduced the adhesion of EPEC to the intestinal cell surface (P) compared to the negative control group<0.05), and 108The composition of probiotic bacteria and 2-FL (5g/L) reduces the adhesion of EPEC to the intestinal cell surface and the effect is more significant (P)<0.01)。
TABLE 6
HN019+ 2' -FL transmembrane resistance test
The preparation steps before the experiment and the specific experimental methods are described in the preceding paragraphs. The tested lactobacillus bifidus HN019 has a normal growth curve.
Results referring to FIG. 7A, the effect of the test substance on transmembrane resistance was tested at different time points, breast milk oligosaccharide 2' -FL alone (5g/L) had essentially no effect on the decrease in transmembrane resistance TEER, close to the negative control group, while probiotic HN019(108) At a plurality of time points, the TEER value of transmembrane resistance tends to be improved to a certain extent; and after the breast milk oligosaccharide 2' -FL is added, the improvement effect is more remarkable at two time points of t-4 and t-5, and the synergistic effect of the combination of prebiotics and probiotics is reflected.
FIG. 7B shows 106The influence of bifidobacterium lactis HN019 in concentration and breast milk oligosaccharide 2' -FL in different concentrations on transmembrane resistance TEER under ETEC invasion conditions, and the data of experimental results (mean ± standard error, repeated three measurements) are shown in table 7. The combination of HN019 and 2-FL (5g/L) tended to increase the TEER value at various time points compared to the probiotic alone. And when t is 2, HN019 (10)6) +2FL (5g/L) is significantly more pronounced than HN019 alone (10)6) High (P)<0.05)。
TABLE 7
4.BL-99+ 2' -FL transmembrane resistance test
The preparation steps before the experiment and the specific experimental methods are described in the preceding paragraphs. The tested bifidobacterium lactis BL-99 has a normal growth curve. The results of the experiment (mean ± standard error, triplicate measurements) are shown in table 8; as shown in fig. 8, BL-99 (10)6) The composition with 2-FL (5g/L) had a tendency to increase the TEER value at various time points compared to the probiotic alone.
TABLE 8
Effect of HN019 and breast milk oligosaccharide 2' -FL on secretion of inflammatory factors IL-8 and IP-10 by intestinal cells
The preparation steps before the experiment and the specific experimental methods are described in the preceding paragraphs. The tested lactobacillus bifidus HN019 has a normal growth curve. Results referring to FIGS. 9, 10, 11 and 12, Bifidobacterium lactis HN019 (10) was cultured without the pathogen ETEC8) And its combination with the breast milk oligosaccharide 2' -FL (5g/L) are significantly lower than ETEC, both releasing IL-8 and IP-10 factors, compared to pathogenic ETEC. When pathogenic bacteria ETEC and a tested substance exist in a cultured system at the same time, the composition of HN019, HN019 and 2' -FL does not affect the release of IL-8, but can obviously reduce the release of IP-10. The HN019+ 2' -FL nutritional composition has a certain regulation effect on the release of inflammatory factors.
FIG. 13 shows 106The influence of bifidobacterium lactis HN019 with concentration and different concentrations of breast milk oligosaccharide 2' -FL on the release of an inflammatory factor IL-8 by intestinal cells Caco-2 under the condition of pathogenic bacteria ETEC invasion is shown in Table 9, and the data of experimental results (mean value +/-standard error, repeated three times of measurement) are shown in the table. As shown in FIG. 13, the combination of HN019 and 2' -FL tended to decrease IL-8.
TABLE 9
Example 2: effect of combination of Bifidobacterium lactis with Breast milk oligosaccharide mixture on gastrointestinal Immunity
Test results of intestinal adhesion of pathogenic bacteria EPEC by combination of HN019 and breast milk oligosaccharide mixture
The preparation steps before the experiment and the specific experimental methods are described in the preceding paragraphs. The tested lactobacillus bifidus HN019 has a normal growth curve. The protective effect of probiotics and prebiotic compositions to prevent pathogenic bacteria from adsorbing to small intestine epithelial cells was investigated by common diarrheagenic strains (EPEC O119).
The results are shown in fig. 14A, the adhesion effect of the breast milk oligosaccharide composition a alone on the pathogenic bacteria escherichia coli O119 on the intestinal tract cells Caco-2 is not significantly different from that of the negative control, and the positive control zinc oxide can significantly reduce the adsorption of the pathogenic bacteria on the intestinal tract cells (p)<0.0001). Probiotics HN019 alone (10)8) The adhesion effect of the pathogenic bacterium Escherichia coli O119 on intestinal tract cells Caco-2 is not significantly different from that of a negative control. However, when prebiotics, i.e. breast milk oligosaccharide composition A, were used as the test substance in the treatment group together with probiotics, both significantly reduced the adsorption of the pathogenic bacterium EPEC 0119 to intestinal cells (p)<0.05)。
FIG. 14B shows the results of a different batch of the test in which different concentrations of Bifidobacterium lactis HN019 and different ratios of HMO mixtures were combined to inhibit the adherence of E.coli EPEC to Caco-2 cells, and the data of the results (mean. + -. standard error, three replicates as shown in Table 10. due to the large number of groups, two different experimental determinations were made1 in 106The mixture of HN019 and composition a at concentration was significantly lower than the negative control (P)<0.05). In experiment 2, 108HN019 at concentration significantly reduced pathogen adherence (P)<0.0001), composition A also significantly reduced pathogenic bacterial attachment (P)<0.0001)，108The combination of HN019 with composition A at concentrations also significantly reduced pathogen adherence (P)<0.0001); composition B significantly reduced pathogen adsorption (P)<0.01)，108The combination of HN019 with composition B at concentrations more significantly reduced pathogen adherence (P)<0.0001), a synergistic effect is embodied; 108The combination of HN019 with composition F at concentrations also significantly reduced pathogen adherence (P)<0.0001)。
Results of intestinal adhesion test of the combination of BL-99 and a mixture of breast milk oligosaccharides on pathogenic bacteria EPEC
The preparation steps and specific experimental methods before the experiment are described in the preceding paragraphs. The tested bifidobacterium lactis BL-99 has a normal growth curve. The protective effect of probiotics and prebiotic compositions to prevent pathogenic bacteria from adsorbing to small intestine epithelial cells was investigated by common diarrheagenic strains (EPEC O119).
The results are shown in fig. 15A, the adhesion of the breast milk oligosaccharide composition B alone to the pathogenic bacteria escherichia coli O119 to the intestinal tract cells Caco-2 is not significantly different from that of the negative control, while the positive control zinc oxide can significantly reduce the adsorption of the pathogenic bacteria to the intestinal tract cells (p)<0.0001). Probiotics BL-99 alone (10)8) The adhesion effect of the pathogenic bacterium Escherichia coli O119 on intestinal tract cells Caco-2 is not significantly different from that of a negative control. However, when prebiotics, i.e. breast milk oligosaccharide composition B, were tested as a treatment group together with probioticsSubstances which, both significantly reduce the adsorption of the pathogenic bacterium EPEC 0119 to the intestinal cells (p)<0.05)。
Fig. 15B shows the results of the experiment of different concentrations of bifidobacterium lactis BL-99 in combination with different proportions of HMO in another batch of experiments on inhibition of the adhesion of e.coli EPEC to Caco-2 cells, with the data of the results (mean ± standard error, three repeated measurements) as shown in table 11. Due to the large number of groups, the test is divided into two different experimental determinations. After comparison of the negative control with the test groups using the Dunnett's posthoc test, it was found that in experiment 1, 106BL-99 in combination with composition A at a concentration significantly lower than the negative control (P)<0.05)，108The mixture of probiotic BL-99 with HMO composition C at concentration has a tendency to reduce the adherence of EPEC. In experiment 2, 108BL-99 at concentrations significantly reduced pathogen adherence (P)<0.01), composition A also significantly reduced the adhesion of pathogenic bacteria (P)<0.01) and 10)8The mixture of BL-99 with composition A at a concentration more significantly reduced the adhesion of pathogenic bacteria (P)<0.0001), a synergistic effect is embodied; 108The mixture of BL-99 with composition B at a concentration significantly reduced pathogenic bacterial adherence (P)<0.001), a synergistic effect is embodied; composition F also significantly reduced pathogen adherence (P)<0.01) and 10)8The mixture of BL-99 with composition F at a concentration more significantly reduced the adhesion of pathogenic bacteria (P)<0.001) exhibiting a synergistic effect.
TABLE 11
Experimental results on the Effect of HN019 in combination with a Breast milk oligosaccharide mixture on transmembrane resistance (TEER)
The preparation steps before the experiment and the specific experimental methods are described in the preceding paragraphs. The tested lactobacillus bifidus HN019 has a normal growth curve.
Results referring to figure 16A, the effect of test substances on transmembrane resistance was tested at different time points, breast milk oligosaccharide combination a alone or probiotic HN019 (10)8) The reduction of transmembrane resistance TEER is basically not influenced and is close to that of a negative control group, and the combination of the probiotic HN019 and the breast milk oligosaccharide mixture A can increase the transmembrane resistance TEER value to a certain extent at a plurality of time points so that the transmembrane resistance TEER value is closer to that of a blank group.
Figure 16B shows another batch of probiotic HN019 alone in the experiment (10)8) The results of the experimental data (mean ± standard error, triplicate measurements) for the effect of HMO composition A, B and F in different proportions on transmembrane resistance TEER in the case of exposure to e.coli ETEC H10407 are shown in table 12. When t is 1, HN019 (10)8) + composition A significantly improved intestinal barrier properties, significantly different from the negative control (P)<0.05). When t is 2, HN019 (10)8) The intestinal barrier property is improved, and the intestinal barrier property is obviously different from that of a negative control (P)<0.01)；HN019(108) + composition A also improved intestinal barrier, with a significant difference from the negative control (P)<0.01)；HN019(108) + composition F improved intestinal barrier, a significant difference from the negative control (P)<0.05). When t is 4, HN019 (10)8) The intestinal barrier property is improved, and the intestinal barrier property is obviously different from that of a negative control (P)<0.05), and HN019 (10)8) + composition A more significantly improved intestinal barrier properties, significantly different from the negative control (P)<0.01), a synergistic effect is embodied; HN019 (10)8) + composition F improved intestinal barrier, a significant difference from the negative control (P)<0.05). When t is 6, HN019 (10)8) + composition A improved intestinal barrier, a significant difference from the negative control (P)<0.01), a synergistic effect is embodied; HN019 (10)8) + composition F also improved intestinal barrier, with a significant difference from the negative control (P)<0.01), a synergistic effect is embodied. Probiotic bacteria HN019 alone were also tested in a two-way ANOVA and Dunnett's posthoc test (10)8) And statistical analysis between different probiotic and HMO combinations, found HN019 (10) at t ═ 68) + composition A: (P<0.05) and HN019 (10)8) + composition F (P)<0.01) are mixed with separate probiotics HN019 (10)8) Has obvious difference and shows synergistic effect.
TABLE 12
Figure 16C shows probiotic bacteria HN019 alone (10)6) The data of the results of the experiments (mean ± standard error, triplicate measurements) with HMO composition a on the effect of transmembrane resistance TEER in the case of exposure to e.coli ETEC H10407 are shown in table 13. When t is 2, HN019 (10)6) + composition A showed a significant increase compared to the negative control (P)<0.05), a synergistic effect is embodied; when t is 4, HN019 (10)6) + composition A with probiotic bacteria HN019 alone (10)6) Compared with the prior art, has obvious improvement (P)<0.05), a synergistic effect is embodied.
Watch 13
Experimental results on the Effect of BL-99 in combination with Breast milk oligosaccharide mixture on transmembrane resistance (TEER)
The preparation steps before the experiment and the specific experimental methods are described in the preceding paragraphs. The tested bifidobacterium lactis BL-99 has a normal growth curve. FIG. 17 shows probiotic BL-99 alone (10)8) The results of the experimental data (mean ± standard error, triplicate measurements) for the effect of HMO composition A, B and F in different proportions on transmembrane resistance TEER in the case of exposure to e.coli ETEC H10407 are shown in table 14. When t is 6, BL-99 (10)8) + composition A significantly improved intestinal barrier properties, significantly different from the negative control (P)<0.05), a synergistic effect is embodied. When t is 4, BL-99 (10)8) + composition B significantly improved intestinal barrier properties, significantly different from the negative control (P)<0.05), a synergistic effect is embodied. When t is 4, and BL-99 (10)8) + combinationThe substance A remarkably improves the intestinal barrier property and is remarkably different from a negative control (P)<0.05)。
TABLE 14
Influence of HN019 and breast milk oligosaccharide mixture on secretion of inflammatory factors IL-8 and IP-10 by intestinal cells
Sound box
The preparation steps before the experiment and the specific experimental methods are described in the preceding paragraphs. The tested lactobacillus bifidus HN019 has a normal growth curve. Results referring to figures 18A, 18B, 19A, 19B, bifidobacterium lactis HN019, and its combination with the breast milk oligosaccharide 2' -FL, released both IL-8 and IP-10 factors at significantly lower levels than pathogenic ETEC without co-cultivation with pathogenic ETEC. And the combination of HN019 with HMO mixtures C and D exhibited some synergistic effect on IL-8 release. When pathogenic bacteria ETEC and a tested substance exist in a cultured system at the same time, the release of IL-8 is not influenced by the composition of HN019, HN019 and HMO mixture C, but the release of IL-8 is obviously reduced by the composition of HN019 and HMO mixture D, and a synergistic effect is presented; furthermore, HN019, and its combination with HMO blends C or D, significantly reduced the release of IP-10. The HN019+ HMO mixture nutritional composition has a certain regulation effect on the release of inflammatory factors.
Example 3 Breast-in-milk infant formula containing HMO and Probiotics
Breast milk infant formula 1 (1000 kg prepared):
1100 kg of raw milk, 330 kg of lactose, 50 kg of whey protein powder WPC 80%, 170 kg of desalted whey powder, 120 kg of high-oleic acid sunflower seed oil, 85 kg of soybean oil, 15 kg of corn oil, 2 kg of soybean phospholipid, 40 kg of galacto-oligosaccharide syrup and 18 kg of compound vitamin. Mixing the above materials, pasteurizing, homogenizing, concentrating by evaporation, spray drying to obtain semi-finished product, and mixing with DHA10 kg, ARA8 kg, and milkFerritin 0.45 kg, HMOs containing 2 '-fucosyllactose (2' -FL) 8.3 kg, and Bifidobacterium lactis 4.5X 106CFU/g (0.15 kg), Bifidobacterium animalis 4.5X 106Mixing the CFU/g and the milk powder by a dry mixer, filling nitrogen into the uniformly mixed milk powder, and packaging to obtain a finished product. The detection shows that the 2' -FL content in the finished product is 1.1 g/L.
Breast milk infant formula 2 (1000 kg prepared):
2700 kg of raw milk, 160 kg of lactose, 70 kg of whey protein powder WPC 34%, 270 kg of desalted whey powder, 90 kg of high-oleic acid sunflower seed oil, 55 kg of soybean oil, 25 kg of corn oil, 2 kg of soybean phospholipid, 38 kg of galacto-oligosaccharide syrup and 9 kg of compound vitamin. Mixing the above materials, pasteurizing, homogenizing, evaporating for concentration, spray drying to obtain powder semi-finished product, and mixing with DHA12 kg, ARA10 kg, lactoferrin 0.45 kg, 2 '-fucosyllactose (2' -FL)7 kg, and Bifidobacterium lactis 4.5 × 106CFU/g (0.15 kg), Bifidobacterium animalis 4.5X 106Mixing the CFU/g and the milk powder by a dry mixer, filling nitrogen into the uniformly mixed milk powder, and packaging to obtain a finished product.
Claims (10)
1. A milk powder for infant comprises milk oligosaccharide and Bifidobacterium lactis.
2. The maternal emulsion infant formula according to claim 1, wherein said Bifidobacterium lactis comprises Bifidobacterium lactis (Bifidobacterium lactis) strain HN019 and/or Bifidobacterium lactis (Bifidobacterium lactis) with accession No. CGMCC No. 15650.
3. The breast milk infant formula of claim 1, wherein the breast milk oligosaccharides comprise one or more of 2 '-fucosyllactose, 3' -fucosyllactose, lacto-N-tetraose, 3 '-sialyllactose, 6' -sialyllactose;
preferably, the breast milk oligosaccharide comprises 2' -fucosyllactose.
4. The breast milk infant formula of claim 3 wherein the breast milk oligosaccharides comprise 2 '-fucosyllactose, 3' -fucosyllactose, lacto-N-tetraose, 3 '-sialyllactose, 6' -sialyllactose in a weight ratio of (0-10): (4-8): (3-6): (1-4): 0-1);
or the breast milk oligosaccharide comprises (by weight percentage) 0-53%, (21-44%), 16-32%, (5-22%) 2 '-fucosyllactose, 3' -fucosyllactose, lacto-N-tetraose, 3 '-sialyllactose, 6' -sialyllactose.
5. The milk-based infant formula of claim 1, wherein the raw materials comprise, in addition to breast milk oligosaccharides and bifidobacterium lactis, the following components in an amount of 1000 parts by weight:
890-3800 parts of raw milk, 0-480 parts of lactose, 0-540 parts of desalted whey powder, 0-80 parts of whey protein powder WPC 80%, 0-120 parts of whey protein powder WPC 34%, 0-170 parts of structural oil OPO0, 0-150 parts of high-oleic acid sunflower seed oil, 0-50 parts of corn oil, 0-50 parts of low erucic acid rapeseed oil, 0-80 parts of soybean oil, 0-23 parts of beta-casein, 1-2.5 parts of soybean lecithin, 0-30 parts of fructo-oligosaccharide powder, 0-90 parts of galacto-oligosaccharide syrup, 1-5 parts of compound vitamin, 0-3 parts of choline chloride, 0-2 parts of mineral substance I and 1-9 parts of mineral substance II; wherein, the first mineral comprises copper, iron and iodine elements, and the second mineral comprises calcium and phosphorus elements;
one or more of the following components can also be optionally included: 0.20-2.04 parts of inositol, 0-0.65 part of taurine, 0.06-0.5 part of L-carnitine, 3-18 parts of DHA, and 3-18 parts of ARA.
6. The maternal emulsion infant formula according to any one of claims 1 to 5, wherein said Bifidobacterium lactis is added in an amount of 1 x 103CFU/g～1×1012CFU/g, preferably 1X 106CFU/g～1×1010CFU/g; the application amount of the breast milk oligosaccharide is 0.5 to 1.5 percent.
7. The maternal emulsion infant formula of any one of claims 1 to 6, further comprising Bifidobacterium animalis in an amount of 1 x 103CFU/g～1×1012CFU/g, preferably 1X 106CFU/g～1×1010CFU/g。
8. A method of preparing a maternal emulsified infant formula according to any one of claims 1 to 7, wherein the maternal emulsified infant formula is prepared by mixing the breast milk oligosaccharides and Bifidobacterium lactis with the other ingredients of the formula using a wet or dry manufacturing process.
9. Use of a maternal emulsified infant formula according to any one of claims 1 to 7 as a food product with the efficacy of increasing the immunocompetence of the gastrointestinal tract.
10. The use of claim 9, wherein the enhancing gastrointestinal immune competence comprises: resist pathogenic bacteria invasion in intestinal tract system, maintain intestinal tract shielding function, and/or reduce release of inflammatory factor IL-8 and/or IP-10 from intestinal tract cells.
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| CN115918916A (en) * | 2022-11-29 | 2023-04-07 | 黑龙江飞鹤乳业有限公司 | Nutritional composition containing breast milk oligosaccharide and lactoferrin, food and application |
| WO2023088290A1 (en) * | 2020-11-16 | 2023-05-25 | 内蒙古伊利实业集团股份有限公司 | Composition containing bifidobacterium lactis and human milk oligosaccharides and application thereof |
| WO2023098518A1 (en) * | 2021-11-30 | 2023-06-08 | 内蒙古伊利实业集团股份有限公司 | Use of bifidobacterium lactis bl-99 in protection of cartilage |
| WO2023098541A1 (en) * | 2021-11-30 | 2023-06-08 | 内蒙古伊利实业集团股份有限公司 | Composition of prebiotic and probiotic capable of enhancing defense of organism against staphylococcus aureus infection |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102481323A (en) * | 2009-07-31 | 2012-05-30 | 雀巢产品技术援助有限公司 | Nutritional Composition For Breast-fed Infants Or Pets With Probiotics And Selected Nutrients |
| CN106615147A (en) * | 2016-09-30 | 2017-05-10 | 建水县鸿辉种养殖产业有限公司 | Baby formula milk powder containing desalted sheep whey powder and production method of baby formula milk powder |
| CN110506793A (en) * | 2019-09-23 | 2019-11-29 | 石家庄君乐宝乳业有限公司 | Breast milk baby formula milk powder containing profitable probliotics and preparation method thereof |
-
2020
- 2020-11-30 CN CN202011369703.3A patent/CN112868800A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102481323A (en) * | 2009-07-31 | 2012-05-30 | 雀巢产品技术援助有限公司 | Nutritional Composition For Breast-fed Infants Or Pets With Probiotics And Selected Nutrients |
| CN106615147A (en) * | 2016-09-30 | 2017-05-10 | 建水县鸿辉种养殖产业有限公司 | Baby formula milk powder containing desalted sheep whey powder and production method of baby formula milk powder |
| CN110506793A (en) * | 2019-09-23 | 2019-11-29 | 石家庄君乐宝乳业有限公司 | Breast milk baby formula milk powder containing profitable probliotics and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 李俊洁;陈庆森;: "双歧杆菌调理和改善肠道相关疾病作用的研究进展", 食品科学, pages 326 - 332 * |
| 魏珣: "快速发展的酸奶市场亟待更有力的科技支撑", 《农经》, pages 46 - 48 * |
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|---|---|---|---|---|
| CN110959676A (en) * | 2018-09-30 | 2020-04-07 | 内蒙古伊利实业集团股份有限公司 | Fermented milk product containing bifidobacterium lactis and application thereof |
| WO2023088290A1 (en) * | 2020-11-16 | 2023-05-25 | 内蒙古伊利实业集团股份有限公司 | Composition containing bifidobacterium lactis and human milk oligosaccharides and application thereof |
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