Coarse cereal composition for preventing or relieving infant food allergy

Abstract

The invention discloses a coarse cereal composition for preventing or relieving infant food allergy, and belongs to the technical field of functional food and special medical food. The invention provides a coarse cereal composition which contains 21 kinds of coarse cereals such as yellow millet, corn, quinoa, oat, red rice, black rice, corn grits, purple rice, buckwheat, proso millet, triticale, white corn grits, white millet, rye, black millet, brown rice, barley, sorghum, highland barley, blood oat and green millet, and can meet the energy and nutritional requirements of infants in the complementary food feeding period. Through verification of OVA-induced weaned mice, the coarse cereal composition can effectively improve individual allergy pathological characteristics, weaken specific immune response intensity, inhibit jejunum epithelial cell damage and intestinal barrier function change, and relieve allergy symptoms. The complementary food composition disclosed by the invention can reduce the food allergy risk of the infants while meeting the energy and nutrition requirements of the infants in the complementary food feeding period, and has a huge application prospect.

Description

Technical Field

[0001] The invention relates to a coarse grain cereal composition for preventing or alleviating food allergies in infants and young children, and belongs to the technical field of functional foods and special medical foods. Background Art

[0002] Allergy refers to an inappropriate immune response initiated by the human immune system to harmless substances in the environment, also known as an allergic reaction. A group of diseases caused by this are called allergic diseases, including asthma, allergic rhinitis and food allergies. With the change of lifestyle, such as improper use of antibiotics, long-term indoor living, little contact with nature and large intake of processed foods, the incidence of allergic diseases is rising sharply around the world. Such diseases are increasingly developing into a serious public health problem. Every year, about 300 million people in the world suffer from bronchial asthma, 500 million people suffer from allergic rhinitis, and 300-500 million people suffer from food allergies. In China, the incidence of allergic diseases is 10-30%, among which infants and young children account for a relatively high proportion. According to statistics, the incidence of allergies in infants and young children aged 0-3 in my country is as high as 41%.

[0003] Due to the incomplete development of the immune system and immature gastrointestinal tract of infants and young children, food allergies are the earliest and most common allergic diseases in this period. Relevant survey data show that the incidence of food allergies in infants and young children in my country has been increasing year by year. In 1999, the incidence of food allergies in infants and young children (<2 years old) was 3.5%, which rose to 7.7% in 2009 and reached 11.1% in 2019. Food allergies not only cause allergic reactions in infants and young children, but may also include skin reactions (such as eczema, urticaria, and redness of the skin), digestive system reactions (such as vomiting, diarrhea, and abdominal pain), and respiratory system reactions (such as wheezing, coughing, and difficulty breathing). In severe cases, it can cause anaphylactic shock and may be life-threatening. Long-term food allergies may also cause feeding difficulties, malnutrition, slow growth, and other problems in infants and young children. It may also affect the development of the immune system and have adverse effects on health in adulthood.

[0004] There are three conventional prevention or treatment methods for food allergies: the first is strict dietary abstinence. The child's allergenic foods are determined through allergen testing or clinical manifestations, and then the type of food is strictly controlled to achieve the purpose of avoiding allergens. This method is direct and effective, but it may delay the development of oral tolerance in infants and young children, and long-term dietary abstinence may lead to malnutrition, and strict dietary restrictions may lead to restrictions on social activities in adulthood; the second method is drug treatment, which generally requires the use of antihistamines and glucocorticoids to relieve symptoms. Severe acute allergic reactions require adrenaline for emergency treatment. Drugs can quickly control allergic symptoms, but drugs have potential side effects. Some drugs, especially new immunotherapy, are costly and difficult to obtain; the third method is desensitization therapy, including oral desensitization therapy, transdermal desensitization therapy, etc. Through long-term treatment, the intensity of allergic reactions in allergic patients can be gradually reduced, but this type of therapy has not yet formed an authoritative and reliable treatment plan, nor has it been widely used.

[0005] At present, the reports on preventing or alleviating infant food allergies through dietary adjustment are mainly prebiotics (especially human milk oligosaccharides) or probiotics. For example, the Chinese invention patent application with publication number CN114886119A discloses the effect of 3'-sialyllactose (one of the structures of human milk oligosaccharides) in alleviating food allergies caused by β-Lg allergens; the Chinese invention patent application with publication number CN117223863A discloses a human milk oligosaccharide composition for alleviating food allergy symptoms, the composition includes 2'-fucoyl lactose, lactose-N-neotetraose, alkoxyglycerol and docosahexaenoic acid. For another example, the Chinese invention patent application with publication number CN117158588A discloses a preparation for improving infant immune imbalance and / or preventing and treating allergic diseases, the preparation includes 3'-sialyllactose, Lactobacillus johnsonii and Lactobacillus reuteri. Literature reports show that (Shumin Wang et al. 2023: Effects of early diet on the prevalence of allergic disease in children: A systematic review and meta-analysis) that supplementing probiotics during complementary feeding for infants and young children at high risk of food allergies can significantly reduce the risk of food allergies (six randomized double-blind placebo-controlled trials with a total of 2,897 participants were included), but for healthy infants (one randomized double-blind placebo-controlled trial and one prospective trial with a total of 8,578 participants were included), there was no significant association between supplementing probiotics during complementary feeding and the occurrence of food allergies in children. In addition, Nestlé has developed a product (product name: SpiceBelle) containing 17 food proteins (eggs, milk, wheat, almonds, cashews, hazelnuts, pecans, pistachios, walnuts, oats, soybeans, shrimp, peanuts, salmon, cod, sesame, rice), which allows infants and young children to ingest a variety of food allergens in trace amounts and for a long time to promote their establishment of immune tolerance, thereby reducing the risk of food allergies in infants and young children.

[0006] Food allergies are incompletely related to the development of the intestinal barrier and immune system in infants and young children. The main function of the intestinal barrier is to prevent harmful substances and pathogens from entering the blood while allowing the absorption of nutrients. In infancy, due to the imperfection of the intestinal mucosal barrier and higher permeability than that of adults, some large molecular proteins may pass through the intestine into the blood, triggering allergic reactions in the immune system. The immune system is still in the process of development during infancy, and the immune system at this stage is more prone to allergic reactions to foreign proteins, especially in the absence of proper immune regulation. This immature immune response may cause allergens to be misidentified as harmful substances, thereby triggering allergic reactions. In addition, the intestinal flora of infants and young children is gradually established and matured in the first few years after birth, and these microorganisms play an important role in the development and regulation of the immune system. Imbalances in the intestinal flora (for example, due to excessive use of antibiotics or inappropriate diet) may affect the development of immune responses and increase the risk of food allergies.

[0007] The active ingredients of whole grain cereals include β-glucan, resistant starch, arabinoxylan, phenolic acid, flavonoids, phytosterols, lignans, anthocyanins, amino acids, minerals and plant proteins. These active ingredients may promote the development of the gastrointestinal tract, immune maturation and healthy development of intestinal flora in infants and young children through multiple intracellular signaling pathways and immunomodulatory effects. Dietary fiber (such as β-glucan and resistant starch) can enhance the tight junctions of intestinal epithelial cells, thereby improving the integrity of the intestinal barrier and preventing allergens from passing through the intestine into the blood to trigger an immune response. These indigestible carbohydrates can also promote the growth of beneficial intestinal bacteria, strengthen the intestinal barrier by producing short-chain fatty acids, and reduce inflammation and allergic reactions. At the same time, the growth of beneficial bacteria is conducive to the evolution and maturation of intestinal flora in a "healthy" way. The intestinal flora is closely related to early immune maturation, and the healthy composition of the intestinal flora also contributes to the maturation of the immune system and the correct immune response. In addition, the antioxidant components in whole grain cereals (such as phenolic acids and flavonoids) help reduce free radical damage, thereby alleviating allergic reactions. Ingredients such as phytosterols and lignans can regulate the activity of immune cells, reduce the release of inflammatory cytokines, and reduce the immune system's overreaction to allergens. Moreover, a variety of whole grain cereals promote the development of oral tolerance in infants and young children. A diverse diet in early life can help the immune system learn to distinguish between harmful and harmless substances, thereby reducing the occurrence of food allergies in later life. Therefore, whole grain cereals have great potential in preventing food allergies in infants and young children. However, there are currently no reports or invention patents on complementary food addition methods, formulas or compositions designed based on whole grain cereals for the prevention or relief of allergic diseases such as food allergies in infants and young children.

[0008] The Huangdi Neijing, an ancient dietary guide in my country, points out: "Five grains are for nourishment, five fruits are for assistance, five animals are for benefit, and five vegetables are for filling." It regards five grains as the basis of diet and the cornerstone of health. Modern scientific diet also advocates the consumption of "five grains". However, there are no clear guidelines for adding grains during the complementary feeding period of infants and young children. Therefore, in actual feeding, each parent can only add and proportion according to personal experience. Moreover, through research, it was found that not all families are aware of feeding infants and young children with grains during the complementary feeding period.

[0009] Therefore, in order to solve the above problems, by developing a complementary food composition rich in whole grains and with a scientific ratio during the feeding process of infants and young children to meet the nutritional and energy needs of infants and young children during the complementary feeding period and achieve the effect of reducing the risk of food allergies, it has broad application prospects and long-term health benefits. Summary of the invention

[0010] [Technical issues]

[0011] The technical problem to be solved by the present invention is to provide a safe, scientific and easy-to-implement composition that can meet the nutritional and energy needs of infants and young children and enhance their tolerance to foods that are likely to cause allergic reactions.

[0012] [Technical solution]

[0013] An object of the present invention is to provide a complementary food composition, which is rich in whole grains and cereals and can meet the nutritional and energy requirements of infants and young children during the complementary food period.

[0014] The invention provides a miscellaneous grain composition, which contains 6.5-43% of yellow millet, 2.4-16% of corn, 1.3-8.5% of quinoa, 1-7% of oats, 1-6.5% of red rice, 0.8-5.7% of black rice, 0.8-5% of corn grits, 0.3-2% of purple rice, 0.2-1.4% of buckwheat, 0.16-1% of rhubarb rice, 0.1-0.7% of black wheat, 0.1-0.7% of white corn grits, 0.1-0.7% of white millet, 0.05-0.4% of rye, 0.05-0.4% of black millet, 0.04-0.3% of brown rice, 0.03-0.2% of barley, 0.02-0.15% of sorghum, 0.02-0.15% of highland barley, 0.02-0.15% of blood oats and 0.01-0.1% of green millet.

[0015] The invention provides a food composition, which is composed of coarse grains and refined grains; the food composition contains (by percentage): 6.5-43% yellow millet, 2.4-16% corn, 1.3-8.5% quinoa, 1-7% oats, 1-6.5% red rice, 0.8-5.7% black rice, 0.8-5% corn grits, 0.3-2% purple rice, 0.2-1.4% buckwheat, 0.16-1% rhubarb rice, and 1% black wheat. 0.1-0.7%, white corn grits 0.1-0.7%, white millet 0.1-0.7%, rye 0.05-0.4%, black millet 0.05-0.4%, brown rice 0.04-0.3%, barley 0.03-0.2%, sorghum 0.02-0.15%, highland barley 0.02-0.15%, blood oats 0.02-0.1%, green millet 0.01-0.1%, and the rest is rice and / or wheat.

[0016] In one embodiment, the coarse grains include 12% yellow millet, 4.5% corn, 2.4% quinoa, 2.0% oats, 1.9% red rice, 1.6% black rice, 1.5% corn grits, 0.6% purple rice, 0.4% buckwheat, 0.3% rhubarb rice, 0.2% black wheat, 0.2% white corn grits, 0.2% white millet, 0.1% rye, 0.1% black millet, 0.08% brown rice, 0.05% barley, 0.04% sorghum, 0.04% highland barley, 0.03% blood oats, and 0.01% green millet; the fine grains include 36% rice and 36% wheat by weight.

[0017] In one embodiment, the coarse grains include 4.3% yellow millet, 1.6% corn, 0.85% quinoa, 0.7% oats, 0.65% red rice, 0.6% black rice, 0.5% corn grits, 0.2% purple rice, 0.14% buckwheat, 0.1% rhubarb rice, 0.07% black wheat, 0.07% white corn grits, 0.07% white millet, 0.04% rye, 0.04% black millet, 0.03% brown rice, 0.02% barley, 0.01% sorghum, 0.01% highland barley, 0.01% blood oats, and 0.005% green millet; the fine grains include 45% rice and 45% wheat by weight.

[0018] In one embodiment, the miscellaneous cereals include 21.4% yellow millet, 8% corn, 4.3% quinoa, 3.5% oats, 3.4% red rice, 3% black rice, 2.5% corn grits, 1% purple rice, 0.7% buckwheat, 0.5% rhubarb rice, 0.3% black wheat, 0.3% white corn grits, 0.3% white millet, 0.18% rye, 0.18% black millet, 0.14% brown rice, 0.1% barley, 0.07% sorghum, 0.07% highland barley, 0.05% blood oats, and 0.01% green millet; the cereals include 25% rice and 25% wheat by weight.

[0019] In one embodiment, the coarse grains include 11.9% yellow millet, 4.5% corn, 2.4% quinoa, 2.0% oats, 1.9% red rice, 1.6% black rice, 1.5% corn grits, 0.6% purple rice, 0.4% buckwheat, 0.3% rhubarb rice, 0.2% black wheat, 0.2% white corn grits, 0.2% white millet, 0.1% rye, 0.1% black millet, 0.08% brown rice, 0.05% barley, 0.04% sorghum, 0.04% highland barley, 0.03% blood oats, 0.01% green millet, 0.01% coix seed, 0.01% red wheat, 0.01% barley kernel, and 0.01% wheat kernel; the fine grains include 36% rice and 36% wheat by weight.

[0020] The present invention also provides a method for adding complementary food, which comprises using the coarse grain cereal composition as complementary food or a part of complementary food, so that the weight of the coarse grain cereal accounts for at least 15% of the total daily cereal intake of infants and young children, and the rest is refined grain cereals.

[0021] In one embodiment, the weight of the coarse grains accounts for 20-50% of the cereal staple food, and the rest is refined grains; the types of the coarse grains are 21 kinds.

[0022] In one embodiment, the weight of the coarse grains accounts for 25-30% of the cereal staple food, and the rest is refined grains; the types of the coarse grains are 21 kinds.

[0023] In one embodiment, the refined grains are rice and / or wheat.

[0024] In one embodiment, the coarse grains can be eaten directly, or added to products such as but not limited to grain powder, flour, fruit and vegetable puree, meat puree, noodles, dumplings, wontons, steamed buns, supplementary food porridge, brown rice rolls, cereal bars, biscuits, rice cakes, etc.

[0025] The present invention also provides the use of the coarse grain composition in preparing a health product that helps to enhance immunity.

[0026] In one embodiment, the application includes but is not limited to relieving individual allergic symptoms caused by ovalbumin (OVA), such as weakness, hypothermia, diarrhea, cyanosis around the mouth and tail, increased respiratory rate, dyspnea, and the like.

[0027] In one embodiment, the use includes but is not limited to reducing the level of allergy-related factors in the serum of individuals with OVA-induced allergy.

[0028] In one embodiment, the application includes but is not limited to inhibiting OVA-induced intestinal epithelial cell damage and intestinal barrier function changes in allergic individuals.

[0029] The present invention also provides application of the complementary food composition in feeding infants and young children during the period of adding complementary food.

[0030] In one embodiment, the infants include but are not limited to healthy infants, infants at high risk of allergic diseases (food allergy, atopic dermatitis, eczema, asthma, etc.), or infants who have experienced food allergy.

[0031] Beneficial effects:

[0032] The food composition provided by the present invention is safe, scientific and operable, can meet the nutritional and energy needs of infants and young children, and can also reduce the risk of food allergies in infants and young children.

[0033] The present invention continuously tracks 40 infants for 18 months, collects dietary information after they start to receive complementary food (food other than breast milk or formula milk powder), and divides them into two groups according to the intake of coarse grains: one rich in coarse grains and one lacking in coarse grains. At the same time, the health of the two groups of infants is recorded, especially the immune response to ingested allergens and inhaled allergens at 18 months of age. Analysis shows that the dietary pattern rich in coarse grains during the complementary food period does not change the weight and height growth rate of infants. From 6 months to 18 months of age, the weight and height growth rates of infants in the group rich in coarse grains are 37.5% and 21.9%, respectively, and those in the group lacking coarse grains are 37.1% and 22.1%, respectively. However, a diet rich in coarse grains during the complementary food period can significantly promote the immune maturation of infants and help infants build tolerance to ingested allergens. At 18 months of age, the incidence of serum total immunoglobulin E (IgE) levels exceeding the normal range in the group rich in coarse grains is 11.8%, and that in the group lacking coarse grains is 31.6%. Changes in IgE levels can reflect the activity of the human immune system, especially in allergic reactions. If the total serum IgE level is significantly increased, it may indicate that the individual has a reaction to one or more allergens, or reflect that the individual has an allergic constitution. At 18 months of age, the incidence of specific allergic reactions in the serum of children in the group rich in whole grains and cereals to fx5e (food mixed allergens) was 21.4%, while that in the group lacking whole grains and cereals was 66.7%, with a significant difference (P = 0.005). In addition, the number of children with specific allergic reactions (the higher the level, the more severe the specific allergic reaction) reaching level 2 or above was higher in the group lacking whole grains and cereals (7.1% and 50% in the group rich in whole grains and cereal ...

[0034] The present invention optimizes the formula of the coarse grain cereal composition and uses the coarse grain cereal composition in the OVA-induced allergic mouse model. The study found that feeding the coarse grain cereal composition of the present invention can effectively improve the allergic pathological characteristics of mice. Compared with the model group, the allergic symptoms such as weakness, cyanosis around the mouth and tail, increased respiratory rate and dyspnea in mice intervened by the coarse grain cereal composition were effectively alleviated; in the stimulation stage, the average rectal temperature of the model group mice decreased by 2.26°C within 30 minutes after oral administration of OVA, and the mice intervened by the coarse grain cereal composition only decreased by 0.2°C, and the low temperature symptoms were significantly alleviated; at the same time, the diarrhea symptoms of mice were also significantly alleviated, and the diarrhea symptom index decreased by 70.4% compared with the model group. The levels of allergy-related factors in the serum of mice intervened by the coarse grain cereal composition were significantly reduced. Compared with the model group, the level of ovalbumin-specific immunoglobulin E (OVA-sIgE) was reduced by 28.7%, the level of mouse mast cell protease (mMCP-1) was reduced by 23.8%, and the levels of (interleukin-4) IL-4 and IL-5 were also significantly reduced, indicating that the intensity of specific immune response was weakened. After OVA sensitization, inflammation may occur in the jejunum, accompanied by epithelial cell damage and changes in intestinal barrier function. Mice treated with the multigrain combination can effectively inhibit intestinal epithelial cell damage and changes in intestinal barrier function, and the villi of the jejunal tissue cells are slender and closely arranged, and the intestinal mucosa and other structures are intact, with no obvious inflammatory response.

[0035] Therefore, the food composition of the present invention has great potential in enhancing tolerance to foods that are prone to cause allergic reactions. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 :Weight of infants in the two groups at 6 and 18 months of age. "ns" means there is no statistically significant difference between the two groups (P>0.05).

[0037] Figure 2 :Height of the two groups of infants at 6 and 18 months of age. "ns" means there is no statistically significant difference between the two groups (P>0.05).

[0038] Figure 3 :The growth rates of weight and height of the two groups of infants from 6 to 18 months of age. "ns" means there is no statistically significant difference between the two groups (P>0.05).

[0039] Figure 4 :The time of complementary food introduction for the two groups of infants. “ns” means there is no statistically significant difference between the two groups (P>0.05).

[0040] Figure 5 :Types of whole grains consumed by infants and young children in the two groups during the complementary feeding period. “**” indicates that the data of the two groups are statistically significantly different (P<0.01).

[0041] Figure 6 :The average daily total intake of whole grains and the average daily intake of each whole grain in the two groups of infants and young children during the complementary feeding period. Among them, "*, **, *** and ****" indicate that the data between the two groups are statistically significantly different, "*" is P<0.05, "**" is P<0.01, "***" is P<0.001, and "****" is P<0.0001. "ns" indicates that there is no statistically significant difference between the two groups (P>0.05).

[0042] Figure 7 : Scoring of allergic symptoms in mice. The scoring criteria for allergic symptoms are as follows: 0, no symptoms; 1, repeated scratching / rubbing around the mouth and nose; 2, swelling / erection of hair / reduced activity around the eyes and mouth and nose, increased respiratory rate; 3, cyanosis around the mouth and tail, difficulty breathing, asthma; 4, no activity / tremor and convulsion after stimulation; 5, shock and death. "* and **" indicate statistically significant differences from the model group data, "*" means P<0.05, and "**" means P<0.01.

[0043] Figure 8 : Rectal temperature of mice.

[0044] Fig. 9 : Mouse diarrhea index. The scoring criteria for diarrhea symptoms are as follows: 0, normal stool; 1, mild diarrhea, soft stool; 2, moderate diarrhea, unformed stool, slight stains around the anus; 3, severe diarrhea, watery stool, severe stains around the anus. "* and ***" indicate statistically significant differences from the model group data, "*" means P<0.05, and "***" means P<0.001.

[0045] Fig.10 : OVA-sIgE levels in mouse serum. "*" indicates statistically significant differences from the model group data, and "*" means P<0.05.

[0046] Fig.11 : Mast cell protease (mMCPT-1) levels in mouse serum. "*, ** and ****" indicate statistically significant differences compared with the model group data, "*" means P<0.05, "**" means P<0.01, and "****" means P<0.0001.

[0047] Fig.12 :Interleukin-4 (IL-4) levels in mouse serum. "** and ****" indicate statistically significant differences compared with the model group data, "**" means P<0.01, and "****" means P<0.0001.

[0048] Fig.13 : IL-5 levels in mouse serum. "** and ****" indicate statistically significant differences from the model group data, "**" means P < 0.01, and "****" means P < 0.0001.

[0049] Fig.14 : IL-13 levels in mouse serum. “*” indicates statistically significant difference from the model group data, “*” means P<0.05.

[0050] Fig.15 : Mouse jejunum tissue sections were scanned and observed using a digital slide scanner after hematoxylin-eosin (H&E) staining. Scale bar = 100 μm. DETAILED DESCRIPTION

[0051] Example 1: Longitudinal Clinical Trial

[0052] In this example, an 18-month longitudinal observational study was designed that included 40 infants. The dietary intake information of infants after the addition of complementary foods (foods other than breast milk or formula milk) and height and weight information at 6 and 18 months of age were collected, the types and weights of whole grain cereals in complementary food intake were analyzed, and the immune responses of infants to ingested allergens and inhaled allergens at 18 months of age were evaluated.

[0053] The experimental procedures in the specific implementation method were reviewed and approved by the Ethics Committee of the Obstetrics and Gynecology Hospital Affiliated to Jiangnan University (Wuxi Maternal and Child Health Hospital), Wuxi, Jiangsu Province.

[0054] In this embodiment, the infant meets the following conditions:

[0055] (1) Healthy full-term infants born naturally;

[0056] (2) The mother is in good health;

[0057] (3) Communication and exchange between permanent residents and their families in Wuxi City, Jiangsu Province is barrier-free;

[0058] (4) Voluntarily comply with and cooperate with follow-up requirements.

[0059] In this example, the infants were excluded from the following criteria:

[0060] (1) High risk of allergy: family history of allergic diseases; showing signs of certain allergic diseases in early infancy (before complementary feeding), such as eczema (atopic dermatitis) or reaction to formula milk;

[0061] (2) Assisted reproduction;

[0062] (3) Twins or more;

[0063] (4) The mother suffers from chronic diseases / infectious diseases / major diseases, or has hypertension, diabetes, etc. during pregnancy;

[0064] (5) The mother received antibiotic treatment for more than 7 days during the perinatal period or lactation period, or the infant received antibiotic treatment for more than 7 days after birth;

[0065] (6) Mothers who have taken probiotic / prebiotic dietary supplements for a long time during the perinatal period or lactation period, or infants who have taken probiotic / prebiotic dietary supplements for a long time after birth;

[0066] (7) The mother or infant is participating in a nutritional or drug intervention study.

[0067] In this embodiment, the types and weights of the whole grains consumed by the infant during the complementary feeding period are calculated based on the dietary information recorded by the infant's parents.

[0068] In this embodiment, according to the ratio of the average daily miscellaneous grains intake to the total grain intake during the complementary feeding period, the infants are divided into a complementary food rich miscellaneous grains group (proportion ≥ 15%) and a complementary food lacking miscellaneous grains group (proportion < 15%).

[0069] Complementary food rich in whole grains: the whole grains consumed include yellow millet, corn, quinoa, oats, red rice, black rice, corn grits, purple rice, buckwheat, rhubarb rice, black wheat, white corn grits, white millet, rye, black millet, brown rice, barley, sorghum, highland barley, blood oats, and green millet.

[0070] In this embodiment, the height and weight information of the infant is obtained by regularly going to the hospital for health check-ups.

[0071] In this example, the method for detecting serum allergic reactions in infants at 18 months of age is shown in Table 1.

[0072] Table 1 Serum allergic reaction detection method

[0073]

[0074] Note: Inhalation allergen screening (phadiatop) includes dust mites, household dust mites, house dust, mixed molds, mixed tree pollens, mixed grass pollens, cat hair and dog hair dander, etc. Ingestion allergen screening (fx5e) includes egg white, milk, cod, wheat, peanuts, and soybeans. The allergen screening results and the corresponding atopic allergy levels are shown in Table 2.

[0075] Table 2 Atopic allergy

[0076]

[0077] The results are as follows:

[0078] Three participants did not undergo allergic reaction testing, and one participant had poor compliance (diet information was not obtained). Finally, the diet and health data of 36 participants were included in the statistics. There were 17 participants in the complementary food rich in whole grains group and 19 participants in the complementary food lacking whole grains group.

[0079] (I) Weight and height and change rate at 6 and 18 months of age

[0080] like Figure 1 As shown in the data, at 6 months of age, the average weight of infants in the group rich in whole grains was 9.0 kg, and the average weight of infants in the group lacking whole grains was 8.8 kg, with no significant difference in weight between the two groups. At this time, the two groups of infants had just started to consume complementary foods or were about to consume complementary foods, and their diet was mainly based on breast milk and / or formula milk powder, supplemented by complementary foods. At 18 months of age, the average weight of infants in the group rich in whole grains was 12.0 kg, and the average weight of infants in the group lacking whole grains was 11.6 kg, with no significant difference in weight between the two groups. At this time, both groups of infants had been adding complementary foods for about a year, supplemented by breast milk and / or formula milk powder, with complementary foods as the main food.

[0081] like Figure 2 As shown in the figure, at 6 months of age, the average height of infants in the group rich in whole grains was 69.3 cm, and the average height of infants in the group lacking whole grains was 68.7 cm, with no significant difference in height between the two groups. At 18 months of age, the average height of infants in the group rich in whole grains was 83.7 cm, and the average height of infants in the group lacking whole grains was 83.2 cm, with no significant difference in height between the two groups.

[0082] like Figure 3 As shown, from 6 to 18 months of age, the average weight gain of infants in the group rich in whole grains was 3.1 kg, a growth rate of 37.5%, and the average height increase was 14.4 cm, a growth rate of 21.9%. The average weight gain of infants in the group lacking whole grains was 2.8 kg, a growth rate of 37.1%, and the average height increase was 14.6 cm, a growth rate of 22.1%. The weight and height growth of the two groups of infants were very similar.

[0083] The results showed that the weight and height of the two groups of infants at 6 and 18 months of age were within the normal range of the "Growth Standards for Children Under 7 Years Old" issued by the National Health Commission, and were close to the median. Whether the staple food during the complementary feeding period is rich in whole grains has no significant effect on the growth of infants' weight and height, and has no adverse effects on the growth of infants.

[0084] (II) Serum allergic reaction test at 18 months of age

[0085] At 18 months of age, the two groups of children underwent serum allergic reaction testing. The results are shown in Table 3. The incidence of total serum IgE levels exceeding the normal range in the children rich in whole grains was 11.8%, and that in the group lacking whole grains was 31.6%. Changes in IgE levels can reflect the activity of the human immune system, especially in allergic reactions. If the serum total IgE level is significantly increased, it may indicate that the individual has a reaction to one or more allergens, or reflects that the individual has an allergic constitution. The incidence of specific allergic reactions to inhaled allergens in both groups of children was extremely low, indicating that the incidence of common clinical diseases such as hay fever, allergic rhinitis, and bronchial asthma is low in children of this age group or region.

[0086] At 18 months of age, the incidence of specific allergic reactions to fx5e (food mixed allergens) in the serum of children in the group rich in whole grains was 21.4%, while that in the group lacking whole grains was 66.7%, with significant differences (P = 0.005). In particular, the differences in specific allergic reactions to ingested allergens between the two groups were mainly at the second level (P = 0.008) and the second level and above (P = 0.009). The higher the level, the more severe the specific allergic reaction. The specific allergic reaction level of children in the group lacking whole grains to ingested allergens was mainly at the second level, while although there were children in the group rich in whole grains who had specific allergic reactions to ingested allergens, they were mainly at the first level. The results show that a diet rich in whole grains during the complementary feeding period can significantly reduce the risk of food allergies.

[0087] Table 3 Serum allergic reaction detection at 18 months of age

[0088]

[0089] Note: ** indicates statistically significant differences.

[0090] The results showed that a diet rich in whole grains during the complementary feeding period can significantly reduce the incidence of food allergies in infants and young children. According to research literature reports, the mechanism by which whole grains reduce the risk of food allergies in infants and young children may include the following pathways. Whole grains can enhance the intestinal barrier function of infants and young children. The dietary fiber (such as β-glucan and resistant starch) in them can enhance the tight junctions of intestinal epithelial cells, thereby improving the integrity of the intestinal barrier and preventing allergens from passing through the intestine into the blood to trigger an immune response. At the same time, these fibers can also promote the growth of beneficial intestinal bacteria, strengthen the intestinal barrier by producing short-chain fatty acids (such as butyrate), and reduce inflammation and allergic reactions. In addition, whole grains can regulate the immune system of infants and young children, and the antioxidant components (such as phenolic acids and flavonoids) in them can help reduce free radical damage, thereby alleviating allergic reactions. Ingredients such as phytosterols and lignans can regulate the activity of immune cells, reduce the release of inflammatory cytokines, and reduce the overreaction of the immune system to allergens. Moreover, a variety of whole grains promote the development of oral tolerance in infants and young children. A diverse diet in early life can help the immune system learn to distinguish between harmful and harmless substances, thereby reducing the occurrence of food allergies in the later stage. Finally, the prebiotic components (non-digestible carbohydrates) in whole grains can promote the growth of beneficial bacteria, such as Bifidobacterium and Lactobacillus, which can reduce the occurrence of allergic reactions through multiple mechanisms. The intestinal flora is closely related to early immune maturation, and a healthy intestinal flora composition also contributes to the maturation of the immune system and the correct immune response.

[0091] (III) Timing of introduction of complementary food, types of grains and their intake

[0092] like Figure 4 As shown in the data, there was no significant difference in the time of complementary food introduction between the two groups of infants. The average time of first complementary food introduction for both groups of infants was 5.8 months old. According to the recommendations of the World Health Organization (WHO), infants can generally start adding complementary food at 6 months old. Complementary food should be added no earlier than 4 months and no later than 8 months. The time of complementary food introduction for both groups of infants was scientific and reasonable.

[0093] In addition, as shown in Table 4, there was no significant difference in the average daily total intake of all cereals between the two groups of infants, but the average daily total intake of coarse grains and their proportion were significantly different between the two groups (P<0.0001).

[0094] Table 4 Intake of all cereals and coarse grains

[0095]

[0096] Note: Values ​​are mean ± standard deviation (SD); **** indicates statistically significant differences.

[0097] like Figure 5As shown in the results, there was a significant difference in the types of whole grains consumed by the two groups of infants during the complementary feeding period (P = 0.0033). The average number of whole grains consumed by infants in the rich whole grains group during the complementary feeding period was as high as 15, while the average number of whole grains consumed by infants in the lack of whole grains group during the complementary feeding period was 9. The prevalence of whole grains consumed by infants in the two groups was significantly different in black rice (P = 0.0013), purple rice (P = 0.0058), buckwheat (P = 0.0058), white millet (P = 0.0411) and rhubarb rice (P = 0.0489).

[0098] like Figure 6 As shown in the figure, the average daily total intake of whole grains by the two groups of infants during the complementary feeding period was significantly different (P<0.0001). The average daily total intake of infants in the group rich in whole grains was 22.77g, while the average daily total intake of infants in the group lacking whole grains was 6.61g. In the group rich in whole grains, the average daily weight of various whole grains consumed by infants from most to least were yellow millet, corn, quinoa, oats, red rice, black rice, corn grits, purple rice, buckwheat, rhubarb rice, black wheat, white corn grits, white millet, rye, black millet, brown rice, barley, sorghum, highland barley, blood oats and green millet. There were significant differences in the average daily weight of various whole grains consumed by infants and young children in the group rich in whole grains and the group lacking in whole grains, including yellow millet (9.61g vs. 2.28g, P<0.0001), corn (3.63g vs. 1.62g, P=0.0496), quinoa (1.93g vs. 0.39g, P=0.0016), red rice, corn grits, purple rice and white corn grits.

[0099] The results showed that there were significant differences between the two groups of infants in the number of types of whole grains, the average daily total intake, and the average daily intake of multiple whole grains during the complementary feeding period. Combined with the results of the serum allergic reaction test of the above-mentioned infants at 18 months of age (Table 3), it shows that a diet rich in whole grains during the complementary feeding period can reduce the risk of food allergies in infants and young children.

[0100] Example 2 Design of coarse grain cereal composition

[0101] A multigrain cereal composition having the formula shown in Table 5 was designed:

[0102] Based on the average intake of whole grains by infants and young children in the whole grain-rich group during the complementary feeding period, examples of whole grain cereal compositions designed for infants and young children during the complementary feeding period are given in Table 5.

[0103] Table 5: Cereal composition designed for infants and young children during the complementary feeding period

[0104]

[0105] Example 3 Effect of the coarse grain composition on improving pathological characteristics of ovalbumin (OVA)-induced allergic mice

[0106] The specific steps are as follows:

[0107] 40 3-week-old SPF weaned BALB / c female mice were divided into 8 groups: (1) control group; (2) model group; (3) coarse grain cereal composition group (coarse grain cereal composition designed in Example 2); (4) ratio group 1; (5) ratio group 2; (6) type group 1; (7) type group 2; (8) type group 3. The feed of each group of mice was isocaloric feed, and the difference was the cereal part in the feed, which consisted of coarse grains and refined grains, as follows:

[0108] Table 6 Overall composition of the grain portion of each group of feed

[0109]

[0110]

[0111] Table 7 Specific composition of the grain portion of each group of feed

[0112]

[0113]

[0114] The experiment lasted for 61 days. On days 1-14, mice were allowed to drink water and eat freely without any special operation. Days 14-28 were the sensitization stage. The first sensitization was performed on day 14 and the enhanced sensitization was performed on day 28. The mice in the control group were intraperitoneally injected with 200 μL phosphate buffered saline (PBS), and the mice in the other 7 groups were intraperitoneally injected with 100 μg ovalbumin (OVA) dissolved in 100 μL PBS and 100 μL aluminum adjuvant. Days 42-60 were the challenge (stimulation) stage. Starting from day 42, each mouse was gavaged with 200 μL PBS containing 50 mg OVA every other day (the mice in the control group were only gavaged with 200 μL PBS), for a total of 7 stimulations. The allergic symptoms, rectal temperature and diarrhea index of the mice were evaluated 1 hour after the last stimulation. On the 61st day, the mice were anesthetized by isoflurane inhalation, blood was drawn from their eyeballs and they were killed by cervical dislocation. Serum was collected to measure the levels of cytokines (IL-4, IL-5 and IL-13), immunoglobulins (OVA-sIgE) and mouse mast cell protease (mMCP-1), and jejunal tissues were collected for histopathological analysis.

[0115] The IL-4, IL-5 and IL-13 as well as OVA-sIgE and mMCP-1 detection kits involved in the examples were purchased from Nanjing Senbeijia Biotechnology Co., Ltd. and operated according to the instructions;

[0116] The jejunal tissue pathology analysis method involved in the embodiment is as follows: after dissection, the jejunal tissue is placed in a 4% paraformaldehyde solution for fixation for 24 hours, dehydrated, transparentized, wax-impregnated, embedded and sliced, and then stained with hematoxylin-eosin (H&E), and then observed by a digital slice scanner.

[0117] The results are as follows:

[0118] (I) Allergy symptom scores, rectal temperature and diarrhea index of mice

[0119] OVA-sensitized mice show a variety of symptoms, including weakness, hypothermia, diarrhea, scratching, and dyspnea, which are typical characteristics of allergic reactions. The mechanism of these symptoms is mainly driven by Th2-type immune response, IgE-mediated mast cell degranulation, and the release of corresponding inflammatory mediators. These phenotypic changes can be used to evaluate the severity of allergic reactions and the effectiveness of intervention measures.

[0120] like Figure 7 As shown, after the 7th oral administration of OVA, the model group had the highest allergy symptom score, and the mice showed swelling / piloerection / reduced activity around the eyes and nose, cyanosis around the mouth and tail, increased respiratory rate, dyspnea, asthma and other symptoms, while the allergy symptoms of mice in the multigrain combination group (28% multigrain ratio, 21 types of multigrain) were effectively alleviated, and the allergy symptoms of mice in the other intervention groups were milder than those in the model group, but there was no statistical significance.

[0121] Depend on Figure 8 It can be seen that the average rectal temperature of mice in the model group decreased significantly (by 2.26℃) within 30 minutes after the 7th oral administration of OVA; the hypothermia symptoms of mice in the coarse grain combination group (cereal ratio 28%, 21 kinds of coarse grains) and ratio group 1 (cereal ratio 10%, 21 kinds of coarse grains) were significantly alleviated. The average rectal temperature of mice in the coarse grain combination group only decreased by 0.2℃ at 15 minutes and then the temperature recovered. The average rectal temperature of mice in ratio group 1 decreased by 0.32℃ at 15 minutes, and it was still 0.1℃ lower than the initial temperature at 30 minutes and then the temperature recovered. There was no significant difference in the overall rectal temperature fluctuations of the two groups of mice and the control group. The rectal temperatures of mice in the other intervention groups decreased to varying degrees compared with those of mice in the control group.

[0122] At the same time, it was observed that the model group mice had obvious diarrhea symptoms such as porridge-like feces around the anus, loose feces without shape, and intestinal contents flowing out. The diarrhea symptoms of mice in the mixed grain combination group (mixed grain ratio 28%, mixed grain types 21 kinds) and the type 3 group (mixed grain ratio 28%, mixed grain types 25 kinds) were significantly alleviated. The diarrhea symptom index of the two groups of mice decreased by 70.4% and 71.4% respectively. The anus was relatively clean, and the feces were soft but granular. The results are as follows Fig. 9 shown.

[0123] (II) Levels of allergy-related factors in mouse serum

[0124] Ovalbumin-specific immunoglobulin E (OVA-sIgE) is an important indicator of IgE-mediated allergic reactions, which reflects the intensity of specific immune responses to OVA antigens in mice. mMCP-1 is a specific marker released after mast cell degranulation, which directly reflects the degree of mast cell activation and allergic reactions. IL-4, IL-5 and IL-13 are typical Th2 immune response markers, reflecting the occurrence, development and severity of allergic inflammation. In order to evaluate the success of the OVA sensitization model and the effectiveness of preventive measures, the levels of the above allergy-related factors in mouse serum were measured.

[0125] like Fig.10 and Fig.11 As shown, the serum OVA-sIgE and mMCP-1 levels of mice in the model group were significantly higher than those in the control group. The levels of the two indicators in the model group were 119.4pg / mL and 130.3pg / mL, respectively, and the levels of the two indicators in the control group were 93.7pg / mL and 43.6pg / mL, respectively. The serum OVA-sIgE levels of mice in the coarse grains combination group (28% of coarse grains, 21 types of coarse grains) and the type 1 group (28% of coarse grains, 3 types of coarse grains) were significantly reduced, and the two groups decreased by 28.7% and 18.9%, respectively. In terms of mMCP-1 levels, the coarse grains combination group (28% of coarse grains, 21 types of coarse grains), the type 1 group (28% of coarse grains, 3 types of coarse grains) and the type 3 group (28% of coarse grains, 25 types of coarse grains) were all significantly reduced, and the three groups decreased by 23.8%, 27.3% and 23.7%, respectively.

[0126] Depend on Fig.12 , Fig.13 and Fig.14 It can be seen that compared with the control group, the levels of IL-4, IL-5 and IL-13 in the serum of the model group mice were significantly increased (IL-4: 179.1pg / mL; IL-5: 10.5pg / mL; IL-4: 29.3pg / mL). The IL-4 level was significantly lower in the mixed grains combination group (mixed grain ratio 28%, 21 kinds of mixed grains) and the ratio 2 group (mixed grain ratio 50%, 21 kinds of mixed grains) than in the model group, which was reduced by 18.7% and 18.9% respectively; the IL-5 level was significantly lower in the mixed grains combination group (mixed grain ratio 28%, 21 kinds of mixed grains) than in the model group; the IL-13 level was significantly lower in the type 3 group (mixed grain ratio 28%, 25 kinds of mixed grains) than in the model group.

[0127] 3. Histological observation of jejunal inflammation

[0128] OVA can induce an immune response in the gastrointestinal mucosa after being absorbed by the gastrointestinal tract. The jejunum is one of the important target organs for food allergy reactions. After OVA sensitization, inflammation may occur in the jejunum, accompanied by epithelial cell damage and changes in intestinal barrier function. Pathological observation of jejunal tissue is one of the important means to verify the success of the model and evaluate the effectiveness of intervention measures.

[0129] like Fig.15 As shown in the figure, the villi of the jejunum in the control group were slender and closely arranged, the intestinal mucosa and other structures were intact, the lamina propria glands were abundant, the goblet cells were more, and no obvious inflammatory response was observed. The jejunal mucosa structure of the mice in the model group was irregular, the intestinal villi were atrophied, the intestinal epithelial cells were reduced, the distance between the intestinal glands in the lamina propria was significantly widened, and obvious inflammatory response occurred. The villi of the jejunal tissue cells of the mice in the coarse grains combination group were slender and closely arranged, the intestinal mucosa and other structures were intact, and no obvious inflammatory response was observed. The distance between the intestinal glands of the mice in the other four intervention groups was still slightly widened, the villi were shorter than those in the control group, and the arrangement was not as tight as that in the control group, but the villus morphology was similar to that in the control group, and the inflammatory response was reduced. This suggests that the grain combination can effectively inhibit intestinal epithelial cell damage and changes in intestinal barrier function during the occurrence and development of food allergies.

[0130] Comprehensive mouse allergy symptom scores, rectal temperature, diarrhea index, serum allergy-related factor levels and histological observations of jejunal inflammation showed that the multigrain cereal composition described in Example 2 (the addition ratio of the multigrain cereal composition was 28%, and the types were 21) was used for feeding weaned mice, which could effectively improve the pathological characteristics of OVA-induced allergic mice. Changing the addition ratio of multigrain cereals or adding types of the composition had a certain degree of allergy relief effect, and the multigrain cereal composition designed in Example 2 had the best effect.

[0131] Although the present invention has been disclosed as above in the form of a preferred embodiment, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

Claims

1. A multi-grain composition, characterized in that: Contains yellow millet 6.5-43%, corn 2.4-16%, quinoa 1.3-8.5%, oats 1-7%, red rice 1-6.5%, black rice 0.8-5.7%, corn grits 0.8-5%, purple rice 0.3-2%, buckwheat 0.2-1.4%, rhubarb rice 0.16-1%, black wheat 0.1-0.7%, white corn grits 0.1-0.7%, white millet 0.1-0.7%, rye 0.05-0.4%, black millet 0.05-0.4%, brown rice 0.04-0.3%, barley 0.03-0.2%, sorghum 0.02-0.15%, highland barley 0.02-0.15%, blood oats 0.02-0.1%, and green millet 0.01-0.1%.

2. The multigrain composition according to claim 1, characterized in that Contains: yellow millet 12%, corn 4.5%, quinoa 2.4%, oats 2.0%, red rice 1.9%, black rice 1.6%, corn grits 1.5%, purple rice 0.6%, buckwheat 0.4%, rhubarb rice 0.3%, black wheat 0.2%, white corn grits 0.2%, white millet 0.2%, rye 0.1%, black millet 0.1%, brown rice 0.08%, barley 0.05%, sorghum 0.04%, highland barley 0.04%, blood oats 0.03%, green millet 0.01%.

3. The multigrain composition according to claim 1, characterized in that Contains: yellow millet 4.3%, corn 1.6%, quinoa 0.85%, oats 0.7%, red rice 0.65%, black rice 0.6%, corn grits 0.5%, purple rice 0.2%, buckwheat 0.14%, rhubarb rice 0.1%, black wheat 0.07%, white corn grits 0.07%, white millet 0.07%, rye 0.04%, black millet 0.04%, brown rice 0.03%, barley 0.02%, sorghum 0.01%, highland barley 0.01%, blood oats 0.01%, green millet 0.005%.

4. The multigrain composition according to claim 1, characterized in that Contains: yellow millet 21.4%, corn 8%, quinoa 4.3%, oats 3.5%, red rice 3.4%, black rice 3%, corn grits 2.5%, purple rice 1%, buckwheat 0.7%, rhubarb rice 0.5%, black wheat 0.3%, white corn grits 0.3%, white millet 0.3%, rye 0.18%, black millet 0.18%, brown rice 0.14%, barley 0.1%, sorghum 0.07%, highland barley 0.07%, blood oats 0.05%, green millet 0.01%.

5. The multigrain composition according to claim 1, characterized in that: Contains: yellow millet 11.9%, corn 4.5%, quinoa 2.4%, oats 2.0%, red rice 1.9%, black rice 1.6%, corn grits 1.5%, purple rice 0.6%, buckwheat 0.4%, rhubarb rice 0.3%, black wheat 0.2%, white corn grits 0.2%, white millet 0.2%, rye 0.1%, black millet 0.1%, brown rice 0.08%, barley 0.05%, sorghum 0.04%, highland barley 0.04%, blood oats 0.03%, green millet 0.01%, coix seed 0.01%, red wheat 0.01%, barley kernel 0.01%, wheat kernel 0.01%.

6. A food composition, characterized in that The invention comprises the coarse grain composition according to any one of claims 1 to 5, coarse grain cereals and fine grain cereals; the fine grain cereals are rice and / or wheat.

7. A food containing the multigrain composition according to any one of claims 1 to 5, characterized in that: The food includes but is not limited to cereal powder, fruit and vegetable puree, meat puree, noodles, dumplings, wontons, steamed buns, complementary food porridge, brown rice rolls, cereal bars, biscuits or rice cakes.

8. Use of the coarse grain composition according to any one of claims 1 to 5 in the preparation of health products that help enhance immunity.

9. The use according to claim 8, characterized in that: The applications include but are not limited to alleviating individual allergic symptoms caused by ovalbumin, or reducing the level of allergy-related factors in individual serum, or inhibiting individual intestinal epithelial cell damage and changes in intestinal barrier function.

10. Use of the multigrain composition according to any one of claims 1 to 5 or the food composition according to claim 6 during the period of adding complementary food to infants and young children.

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