Muscle inositol and prevention of accelerated growth

Abstract

The present invention relates to a composition for preventing accelerated growth of offspring comprising a combination of Lactobacillus and Bifidobacterium, myo-inositol, and at least one vitamin selected from the group consisting of vitamin B2, vitamin B6, vitamin B12, vitamin D and mixtures thereof, and wherein the composition is administered to the mother of the offspring before and / or during pregnancy and / or during lactation. The invention also relates to a multi-component kit for preventing accelerated growth of offspring.

Description

Technical Field

[0001] The present invention relates to a composition for preventing accelerated growth of an offspring, the composition comprising a combination of Lactobacillus and Bifidobacterium, inositol, and at least one vitamin selected from vitamin B2, vitamin B6, vitamin B12, vitamin D, and mixtures thereof, and wherein the composition is administered to the mother of the offspring during pre-pregnancy and / or pregnancy and / or lactation. The present invention also relates to a multi-component kit for preventing accelerated growth of an offspring. Background Art

[0002] Generally, it is recommended that women take good care of themselves during pregnancy to prevent complications. Taking good care should include ensuring optimal nutrition. Generally speaking, there is increasing scientific evidence that prenatal nutrition affects long-term growth, development, and health programming, and affects the risk of developing chronic diseases. Several studies have shown that changes in dietary intake or control of various macronutrients and micronutrients during pre-pregnancy and pregnancy can affect several physiological processes of the offspring, such as growth, metabolism, appetite, cardiovascular function, etc. (Koletzko B et al. (2011) Am J Nutr 94(s):2036-43S).

[0003] Therefore, the nutritional status (nutrient reserves and dietary intake) and metabolic status of women during pre-pregnancy, pregnancy, and lactation are related to optimizing neonatal and childhood health outcomes. Maternal nutrition is thought to affect the availability and supply of nutrients required for key developmental processes in the developing fetus, and examples of the effects of prenatal nutritional supplements on the growth of offspring after birth have been published (Lu WP et al. PLoS One. 2014:9.2; Bergmann RL et al. Journal of perinatal medicine. 2012:40(6):677-684).

[0004] A wide variety of nutrients have been used in compositions for maternal administration, and various nutritional compositions have been developed to address maternal nutritional needs. These compositions typically contain mixtures of vitamins and minerals.

[0005] However, for the benefit of the mother and her offspring, it remains useful to select nutritional supplements tailored to the nutritional needs of women during pre-pregnancy, pregnancy, and lactation, specifically targeting this particular group's nutritional status.

[0006] Normal growth refers to the progression of changes in height, weight, and head circumference that conform to the established standards of a given population. Normal growth is a reflection of overall health and nutritional status. Most healthy infants and children grow in a predictable manner and stabilize within the normal percentile range on the standard growth curve. Sometimes, growth in weight, height, or head size may deviate, and an undesired rapid deviation from the expected growth trajectory can have a negative impact on future development and health. Growth problems refer to an infant or child being below or above the average growth range for the infant's or child's age, gender, family history, or ethnic background. It has been demonstrated that growth in the early life can affect long-term health. In particular, accelerated growth in the early postnatal period increases the risk of long-term obesity (Druet C et al., Paediatric and perinatal epidemiology. 2012;26(1):19-26; Singhal A, Ann Nutr Metab. 2017;70:236-240) and is associated with risk factors for both cardiovascular and metabolic outcomes in preschool children (Li N et al., Asia Pac J Clin Nutr. 2020;29(3):558-565). Importantly, the phenomenon of accelerated growth can be observed in healthy children who experience accelerated increases in postnatal weight or length due to genetic predisposition or due to nutritional factors, but can also be observed in those children who have a certain level of growth retardation due to prenatal or postnatal nutritional insults (Singhal A, Ann Nutr Metab. 2017;70:236-240).

[0007] Nutrition is one of the factors that affect infant growth and development. However, no maternal nutritional intervention has been developed that specifically helps prevent accelerated growth in the early life or childhood. Therefore, such an available intervention is desired.

[0008] In addition, a combination of optimal nutrition during the pre-pregnancy and / or during pregnancy and / or during lactation with a composition that may help prevent accelerated growth in the offspring would also be desired.

[0009] Therefore, an object of the present invention is to enrich or improve the prior art and in particular to provide a maternal composition for preventing accelerated growth in the offspring.

[0010] The publications discussed herein are provided only for their disclosure prior to the filing date of the present patent application. Nothing herein is to be construed as an admission that such publications constitute prior art to the claims appended hereto. Summary of the Invention

[0011] The object of the present invention is achieved by the subject matter of the independent claims. The dependent claims further develop the concept of the present invention.

[0012] The present inventors have found that a composition comprising a combination of probiotics, myo-inositol, and other nutrients administered to a mother during pre-pregnancy and / or pregnancy and / or lactation can have a beneficial effect in preventing accelerated growth of her offspring.

[0013] Accordingly, in a first aspect, the present invention provides a composition for preventing accelerated growth of an offspring, the composition comprising a combination of Lactobacillus and Bifidobacterium probiotics, myo-inositol, and at least one vitamin selected from vitamin B2, vitamin B6, vitamin B12, vitamin D, and mixtures thereof, and wherein the composition is administered to the mother of the offspring during pre-pregnancy and / or pregnancy and / or lactation.

[0014] The present invention also provides a multi-component kit for preventing accelerated growth of an offspring, the multi-component kit containing at least two physically separated compositions, each composition comprising at least one component selected from vitamin B2, vitamin B6, vitamin B12, and vitamin D, at least one of the separated compositions comprising myo-inositol and at least one of the separated compositions comprising a combination of Lactobacillus and Bifidobacterium probiotics, wherein the two physically separated compositions are administered to the mother of the offspring during pre-pregnancy and / or pregnancy and / or lactation. Detailed Description

[0015] Definition

[0016] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0017] The term "infant" means a human subject under 12 months of age or a non-human animal of comparable age.

[0018] As used herein, the term "toddler" or "toddler child" can mean a human subject between 12 months and 5 years of age. Appropriately, "toddler" can refer to a non-human animal of comparable age.

[0019] The expression "subsequent life" includes childhood and adulthood. For example, "subsequent life" can refer to childhood, such as at least 1 year, 2 years, at least 3 years, at least 4 years, or at least 5 years. "Subsequent life" can refer to adolescence or young adulthood.

[0020] As used herein, the term "subject" refers to a mammal, and more specifically a cat, dog, or human. A human can be a female, such as a female who wants to become pregnant, a pregnant female, or a lactating female. In an embodiment of the present invention, the subject is a mammal selected from a cat, a dog, and a human. For example, the subject can be a female who is trying to become pregnant, or a pregnant female, or a lactating female.

[0021] In the context of the present invention, the expression "accelerated growth" refers to a rapid increase in the weight, length or body mass index (BMI) of an infant or young child, and is defined as an increase of 0.67 standard deviation (SD) score or more in weight, length or BMI between birth and 1 year of age, or between birth and 2 years of age, or between birth and 5 years of age, which corresponds to crossing one or more percentile bands upwards on a standard growth chart (such as the World Health Organization Child Growth Standards), i.e., from the second percentile to the ninth percentile, from the ninth percentile to the 25th percentile, from the 25th percentile to the 50th percentile, and so on. BMI is the weight of a person measured in kilograms (or pounds) divided by the square of the height measured in meters (or feet). A high BMI may indicate high body fat. The risk of accelerated growth is assessed from birth to 1 year of age and from birth to 2 years of age.

[0022] In the context of the present invention, the expression "nutritional composition" refers to a composition for nourishing a subject. The nutritional composition is typically ingested orally or by intravenous injection. It may comprise a lipid or fat source, a carbohydrate source and / or a protein source.

[0023] In the context of the present invention, the term "nutrient" or "nutrients" is intended to include both macronutrients (such as carbohydrates, proteins or fats) and micronutrients (such as minerals or vitamins) for the human body and their components (such as fatty acids, amino acids).

[0024] In the context of the present invention, the term "ingredient" or "ingredients" refers to an edible substance or a mixture of substances that contains or consists essentially of nutrients for the human body.

[0025] In the context of the present invention, the expressions "in the prevention of", "to prevent" or "for the prevention of" are used interchangeably. They should be understood to include reducing the severity of a disease process. These expressions also cover alleviating the symptoms induced by the disease, such as stress and / or reducing the complications caused by the disease.

[0026] As used in this specification, the terms "comprise", "comprises", "comprising", etc. should be understood in an inclusive sense, rather than an exclusive or exhaustive sense; that is, they mean "including but not limited to".

[0027] As used herein, "about" shall be understood to mean a number within a range of a numerical value, such as a range of -10% to +10% of the recited number, within a range of -5% to +5% of the recited number, or in one aspect within a range of -1% to +1% of the recited number, and in a particular aspect within a range of -0.1% to +0.1% of the recited number. In addition, all numerical ranges herein shall be understood to include all integers or fractions within that range. Further, these numerical ranges shall be understood to provide support for claims involving any number or subset of numbers within that range. For example, the disclosure of 1 to 10 shall be understood to support ranges such as 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc.

[0028] As used herein, the terms "in particular" or "more particularly" shall not be considered restrictive, but rather shall be construed as synonymous with "for example" or "especially".

[0029] As used in this specification, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a component" or "the component" includes two or more components.

[0030] Unless otherwise indicated, all percentages are by weight.

[0031] Unless otherwise defined, all technical terms have and shall be given the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0032] The term dry weight refers to a measurement of the mass of a substance when completely dried and all fluids have been removed from the substance. The dry weight % of a substance refers to the relative amount of the said substance in the total dry matter. As used in this specification, the expressions "weight %" and "wt %" are synonymous.

[0033] It should be noted that the various features, aspects, embodiments and implementations described in the present invention can be compatible and / or can be combined together.

[0034] Other definitions and / or explanations are provided in the following detailed description.

[0035] Embodiments of the present invention

[0036] The present invention will now be described in more detail.

[0037] In a first aspect, the present invention relates to a composition for preventing accelerated growth of offspring, the composition comprising a combination of Lactobacillus and Bifidobacterium probiotics, myo-inositol, and at least one vitamin selected from vitamin B2, vitamin B6, vitamin B12, vitamin D, and mixtures thereof, and wherein the composition is administered to the mother of the offspring during pre-pregnancy and / or pregnancy and / or lactation.

[0038] In an embodiment, the composition thus reduces the risk of experiencing an excessive amount of fat in subsequent life. In particular, it reduces the risk of experiencing an excessive amount of fat at 1 year and 2 years of life by reducing the risk of accelerated growth from birth to 1 year of life and from birth to 2 years of life.

[0039] Advantageously, the composition according to the present invention is administered to the mother during pre-pregnancy, and / or during pregnancy, and / or during lactation, thereby providing a customized nutritional supplement that prevents accelerated growth of her offspring.

[0040] Myo-inositol or cis-1,2,3,5-trans-4,6-cyclohexanehexol is the major isomeric form of inositol. Myo-inositol is a compound present in animal and plant cells and serves as the structural basis for second messengers in eukaryotic cells, particularly as inositol triphosphate (IP3), phosphatidylinositol phosphates (PIP2 / PIP3), and inositol oligosaccharides, playing important roles in various cellular processes. Related studies have shown that myo-inositol is involved in multiple biological processes, such as cell growth and survival, development and function of the peripheral nervous system, osteogenesis, energy metabolism, and reproduction (Croze et al. Biochimie. 2013:95:1811-1827). Myo-inositol has been found to be present as a free form, phosphoinositides, and phytic acid in fresh fruits and vegetables and all foods containing seeds (legumes, cereals, and nuts) (Clements RS and Darnell B., Am J Clin Nutr. 1980:33:1954-1967). Myo-inositol from phytic acid can be released into the intestine by phytases found in plants, microorganisms, and animal tissues (Schlemmer U et al. Mol Nutr Food Res. 2009:53:S330-S375). These enzymes are capable of releasing free inositol, orthophosphate, and intermediate products, including mono-, di-, tri-, tetra-, and pentaphosphate forms of inositol. A large intake of inositol hexaphosphate is hydrolyzed to inositol. Myo-inositol is also commercially available from several suppliers.

[0041] Myo - inositol can be administered in any effective amount according to the present invention. Generally, the effective amount will depend on the type, age, body size, health status, lifestyle, and / or genetic inheritance of the subject. The effective amount can be divided into several smaller amounts and administered throughout the day such that the total daily intake is the effective amount. A person skilled in the art will be able to propose an appropriate amount of myo - inositol for daily consumption. For example, the composition used according to the present invention can provide myo - inositol in an amount of 0.2 to 5 g, preferably 1.5 to 5 g, more preferably 2 to 5 g, and most preferably 2 to 4 g in a daily dose.

[0042] Suitably, the composition used according to the present invention further comprises a combination of Lactobacillus and Bifidobacterium probiotics. Combining myo - inositol with probiotics is particularly beneficial because probiotics have been found to improve intestinal barrier function and facilitate the passage of nutrients through the gut (Cani PD et al. Gut. 2009:58:1091 - 1103). Thus, combining myo - inositol with probiotics can enhance the absorption of myo - inositol and other nutrients that may be present in the composition.

[0043] The term "probiotic" means a preparation of microbial cells or components of microbial cells that have a beneficial effect on the health or well - being of the host (Salminen S, Ouwehand A, Benno Y et al. "Probiotics: how should they be defined" Trends Food Sci. Technol. 1999:10107 - 10). The microbial cells according to the present invention are generally bacteria. In the context of the present invention, the expression probiotic refers to live probiotic bacteria, non - replicating probiotic bacteria, dead probiotic bacteria, non - viable probiotic bacteria, fragments of probiotic bacteria (such as DNA), metabolites of probiotic bacteria, cytoplasmic compounds of probiotic bacteria, cell wall materials of probiotic bacteria, culture supernatants of probiotic bacteria, and / or any combination of the foregoing. Probiotics can be, for example, live probiotics, non - replicating probiotics, dead probiotics, non - viable probiotics, or any combination thereof. In one embodiment of the present invention, the probiotic is a live probiotic.

[0044] The term "cfu" should be understood as colony - forming unit.

[0045] In some embodiments, the Lactobacillus strain is a Lactobacillus rhamnosus strain available under deposit number CGMCC 1.3724, and the Bifidobacterium is a Bifidobacterium lactis BB12 strain deposited as CNCM I-3446. Preferably, the composition comprises a combination of a Lactobacillus rhamnosus strain available under deposit number CGMCC 1.3724 and a Bifidobacterium lactis BB12 strain deposited as CNCM I-3446. Most preferably, the combination of probiotics consists of a combination of a Lactobacillus rhamnosus strain available under deposit number CGMCC 1.3724 and a Bifidobacterium lactis BB12 strain deposited as CNCM I-3446. In a preferred embodiment, the probiotics are provided in the following amounts: 10 5 to 10 12 colony forming units (cfu) in the daily dose, more preferably 10 7 to 10 11 cfu.

[0046] Suitably, the composition used according to the invention further comprises a combination of vitamins. Suitably, the composition may comprise at least one vitamin selected from the group consisting of vitamin B2, vitamin B6, vitamin B12, vitamin D and mixtures thereof. For example, the composition comprises vitamin B2, vitamin B6, vitamin B12 and vitamin D. Preferably, the vitamin D is vitamin D3.

[0047] The inventors were able to demonstrate (Crozier SR et al., Am J Clin Nutr. 2012:96:57–63; Godfrey KM et al., Diabetes. 2011:60:1528–34; Childs C et al., J Dev Orig Health Dis. 2015:6(Suppl 2):S36.) that pregnant women are generally more deficient in vitamins B6, B12 and D compared to other nutrients. In addition, they found that a large proportion of the pregnant population fails to consume sufficient amounts of vitamin B2. Therefore, it is of particular interest to supplement the diet of pregnant women with these vitamins to compensate for these particularly frequent deficiencies.

[0048] If present, preferably vitamin B2 is provided in the following amounts: 0.14 mg to 14 mg in the daily dose. If present, preferably vitamin B6 is provided in the following amounts: 0.19 mg to 19 mg in the daily dose. If present, preferably vitamin B12 is provided in the following amounts: 0.26 μg to 26 μg in the daily dose. If present, preferably vitamin D is provided in the following amounts: 1.5 μg to 100 μg in the daily dose. Most preferably, the composition used according to the invention comprises 1.8 mg of vitamin B2, 2.6 mg of vitamin B6, 5.2 μg of vitamin B12 and 10 μg of vitamin D in the daily dose.

[0049] In some embodiments, the composition used according to the invention may comprise inositol, vitamin B2, vitamin B6, vitamin B12, vitamin D, and a combination of a Lactobacillus rhamnosus strain obtainable under deposit number CGMCC 1.3724 and a Bifidobacterium lactis BB12 strain deposited as CNCM I - 3446.

[0050] In some embodiments, the composition used according to the invention may comprise 0.2 g to 5 g of inositol, 0.14 mg to 14 mg of vitamin B2, 0.19 mg to 19 mg of vitamin B6, 0.26 μg to 26 μg of vitamin B12, 1.5 μg to 100 μg of vitamin D, 10 5 cfu to 10 12 cfu of Bifidobacterium lactis BB12 CNCMI - 3446 and 10 5 cfu to 10 12 cfu of Lactobacillus rhamnosus CGMCC 1.3724, all amounts being defined per daily dose. Suitably, the offspring whose accelerated growth is to be prevented can be an infant, a toddler or a young child.

[0051] Suitably, the composition used according to the invention prevents accelerated growth of the offspring during early life and / or childhood.

[0052] In some embodiments of the present invention, accelerated growth occurs during the first 2 to 5 years of the life of the offspring, such as during the first 2 to 4.5 years of life, or during the first 2 to 4 years of life, such as during the first 2 to 3.5 years of life. For example, accelerated growth can occur in offspring at 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 18 months, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, or 5 years of age. In some embodiments, prevention of accelerated growth can occur in offspring at 5 years, or 4.5 years, or 4 years, or 3.5 years, or 3 years, or 2.5 years, or 2 years, or 18 months, or 12 months, or 9 months, or 6 months, or 3 months, or 2 months, or 1 month of age. Prevention of accelerated growth can occur in offspring between 12 months and 5 years of age, such as between 18 months and 4.5 years of age, or between 2 years and 3.5 years of age. In other embodiments, accelerated growth can occur in offspring up to 5 years, or up to 4.5 years, or up to 4 years, or up to 3.5 years, or up to 3 years, up to 2.5 years, or up to 2 years, or up to 18 months, or up to 12 months, or up to 9 months of age. In yet another embodiment, accelerated growth can occur in offspring between 1 month and 5 years of age.

[0053] The inventors have also demonstrated (Patent No. 14719) that zinc deficiency is common in at least some groups of pregnant women, even to a lesser extent than vitamin B2, vitamin B12, vitamin B6, and vitamin D. Zinc is known to play a role in immune function, protein synthesis, DNA synthesis, and the catalytic activity of various enzymes during growth and development in pregnancy, childhood, and adolescence, and zinc deficiency during pregnancy can lead to growth restriction in infants. Therefore, it is particularly advantageous to supplement zinc in the diet of pregnant women. Thus, in some embodiments, the composition used according to the present invention can comprise zinc. Zinc can be present in the following amounts: 1.1 mg to 40 mg in the daily dose.

[0054] Other vitamins and minerals may also be added. For example, vitamins and minerals may be added according to the recommendations of government agencies such as the USRDA. For example, the composition may contain one or more of the following micronutrients: calcium, magnesium, phosphorus, iron, zinc, copper, iodine, selenium, vitamin A or retinol activity equivalents (RAE) in the form of, for example, β-carotene or a mixture of carotenoids, vitamin C, vitamin B1, niacin, folic acid, biotin, vitamin E. Preferably, the composition may contain one or more of the following micronutrients in the following amounts: 100 mg to 2500 mg calcium, 35 mg to 350 mg magnesium, 70 mg to 3500 mg phosphorus, 2.7 mg to 45 mg iron, 1.1 mg to 40 mg zinc, 0.1 mg to 10 mg copper, 22 μg to 1,100 μg iodine, 6 μg to 400 μg selenium, 77 μg to 3000 μg vitamin A or retinol activity equivalents (RAE) in the form of, for example, β-carotene or a mixture of carotenoids, 8.5 mg to 850 mg vitamin C, 0.14 mg to 14 mg vitamin B1, 1.8 mg to 35 mg niacin, 60 μg to 1000 μg folic acid, 3 μg to 300 μg biotin, 1.9 μg to 109 μg vitamin E.

[0055] The composition used according to the present invention may advantageously further comprise at least one oil selected from long-chain polyunsaturated fatty acids in any suitable amount known to those skilled in the art (for example, an amount between 100 mg and 500 mg, more preferably between 200 mg and 400 mg in the daily dose), such as arachidonic acid (ARA), eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA).

[0056] Any nutrient mentioned herein may be used in any amount that effectively achieves the purpose of the present invention. Those skilled in the art will be able to determine the appropriate dosage. Generally, the dosage will depend on the mother's age, body size, health status, lifestyle and genetic inheritance.

[0057] Generally, the amount defined in this application is the amount of the daily dose. Therefore, the amount of the nutrient in each composition can be selected accordingly depending on whether it is intended to be used once a day or more frequently or less frequently.

[0058] The nutrient may be provided as a sustained-release preparation. If so, the frequency of using the nutrient can be reduced while the body can still continuously obtain an adequate supply of the nutrient.

[0059] In some embodiments, the composition used according to the present invention further prevents the offspring from developing metabolic disorders in subsequent life by preventing accelerated growth of the offspring. Therefore, the present invention has beneficial effects on the mother and on the development of the offspring in its early and late stages.

[0060] Suitably, the metabolic disorders that may develop in subsequent life are cardiometabolic disorders, obesity, excess fat mass accumulation, and overweight.

[0061] Cardiometabolic disorders can be hypertension, hypertriglyceridemia, high diastolic blood pressure, or systolic blood pressure (Li N et al. Asia Pac J Clin Nutr. 2020;29(3):558 - 565).

[0062] "Obesity" refers to a condition in which the natural energy reserve stored in the adipose tissue of animals (especially humans and other mammals) increases to an extent associated with certain health conditions or an increased mortality rate. "Obese" is defined as an individual having a BMI greater than 30. "Overweight" is defined as an individual having a BMI exceeding 25.

[0063] For children, the BMI is plotted on a chart of the standard relationship between BMI and age growth (for girls or boys) to obtain a percentile ranking. Percentiles are the most commonly used indicators for assessing the body size and growth pattern of individual children. Percentiles indicate the relative position of a child's BMI among children of the same sex and age. If the BMI of children and adolescents aged 2 to 19 years is between the 85th percentile and the 95th percentile, they are considered overweight, respectively. If the BMI of children and adolescents aged 2 to 19 years is at or above the 95th percentile, or equal to the 95th percentile, or the absolute BMI is equal to or greater than 30 kg / m2 (whichever is lower), they are considered obese.

[0064] The metabolic disorders associated with overweight, obesity, and / or excessive fat accumulation are similar and well-known to those skilled in the art. For example, these disorders include cardiovascular diseases such as coronary heart disease, insulin resistance, type 2 diabetes, hypertension, sleep apnea, respiratory diseases, and / or dyslipidemia; and also include certain cancers (such as endometrial cancer, breast cancer, and / or colon cancer), stroke, liver, non-alcoholic fatty liver, and gallbladder diseases; osteoarthritis; and / or gynecological diseases.

[0065] The development of metabolic disorders associated with accelerated growth is typically observed in early childhood (e.g., around 5 years of age), in studies of adolescents and young adults during puberty (Li N et al. Asia Pac J Clin Nutr. 2020;29(3):558 - 565); Sutharsan R et al. Journal Health Population and Nutrition. 2015;33:13). However, the development of metabolic disorders associated with accelerated growth can start before 5 years of age, for example, at 1 year, 2 years, 3 years, or 4 years.

[0066] Suitably, prevention of the development of metabolic disorders in the offspring during subsequent life can be observed in early childhood, e.g., around 1 year, 2 years, 3 years, 4 years or 5 years of age.

[0067] In some embodiments, the composition used according to the invention can be intended for maternal administration. This means that the composition can be administered to a female subject who desires to become pregnant (especially during the pre-pregnancy period), to a pregnant female subject (especially during the pregnancy period), or to a female subject who has given birth (especially during the lactation period).

[0068] In some embodiments, the female subject is a mammal, such as a mammal selected from cats, dogs, and humans.

[0069] Suitably, the female subject can be the mother of the offspring.

[0070] Suitably, the composition can be administered to a female who desires to become pregnant and / or to a pregnant female and / or to a lactating female. Preferably, the composition used according to the invention is for administration to a female who desires to become pregnant and / or to a pregnant female, and most preferably to a pregnant female.

[0071] The inventors have found that administration of the composition according to the invention to the mother of the offspring during the pre-pregnancy period and / or during pregnancy and / or during the lactation period prevents accelerated growth of her offspring. In some embodiments, the composition used according to the invention is administered to the mother of the offspring during the pre-pregnancy and / or pregnancy and / or lactation period. Preferably, the composition used according to the invention is administered to the mother of the offspring during the pre-pregnancy and / or pregnancy period.

[0072] In some embodiments, the composition used according to the invention can be administered to the mother during the pre-pregnancy period, e.g., during at least 1, 2, 3, or 4 months before pregnancy or before the desired pregnancy. Suitably, when the composition is for administration to the mother during pregnancy, the composition is preferably administered for at least 4 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, at least 24 weeks, at least 28 weeks, at least 36 weeks during pregnancy.

[0073] With the increasing nutritional requirements during the second and third trimesters of pregnancy, in some embodiments of the invention, the composition used according to the invention is administered throughout the second and third trimesters of pregnancy.

[0074] In some embodiments, the compositions used according to the present invention can be administered to the mother during lactation, for example, during at least 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months after childbirth. Suitably, when the composition is used for administration to the mother during lactation, the composition is administered for at least 4 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, at least 24 weeks, at least 28 weeks, at least 36 weeks during lactation.

[0075] It is important that women who expect to become pregnant prepare their bodies for pregnancy by consuming appropriate nutrients, as a woman's nutrient requirements increase during pregnancy. The compositions used according to the present invention are specifically designed to meet the needs of women during these periods, for example, before pregnancy and during pregnancy and immediately after childbirth.

[0076] The composition can be in any form suitable for administering all the ingredients. Suitably, the composition used according to the present invention can be in the form of a powdered nutritional composition that can be reconstituted in milk, water or any liquid, a food product, a beverage, a nutritional supplement or a nutraceutical.

[0077] When the composition is in the form of a powdered nutritional composition for reconstitution in milk or water, it preferably contains a protein source, a carbohydrate source and a lipid source, preferably together with lecithin. The composition may also include soy lecithin and / or a bulking agent. The protein source can be milk powder or skim milk powder. Sucrose and / or maltodextrin can be used as the carbohydrate source. The lipid source can be vegetable oil. The formulation may also alternatively or additionally contain glucose syrup, milk fat, magnesium citrate, choline salts and choline esters, prebiotic fiber and / or ascorbyl palmitate. For example, flavoring compounds (such as cocoa powder or honey) can be added to provide different flavors.

[0078] The composition can be any type of composition suitable for consumption by the subject to whom the composition is administered.

[0079] The composition can also be a product selected from the group consisting of: nutritional products, functional food products, geriatric care products, dairy products, dairy alternative products, beverage products, diet products and pet food products.

[0080] As used herein, the term "nutritional product" means any product that can be used to provide nutrition to a subject. Generally, nutritional products contain a protein source, a carbohydrate source and a lipid source.

[0081] As used herein, the term "food product" refers to any type of product that is safe for human or animal consumption. The food product can be in solid, semi-solid or liquid form and can contain one or more nutrients, foods or nutritional supplements. For example, the food product can additionally contain the following nutrients and micronutrients: protein sources, lipid sources, carbohydrate sources, vitamins and minerals. The composition can also contain antioxidants, stabilizers (when provided in solid form) or emulsifiers (when provided in liquid form).

[0082] As used herein, the term "functional food product" refers to a food product that provides an additional health-promoting or disease-preventing function for an individual.

[0083] As used herein, the term "geriatric care product" refers to a product that provides an additional health-promoting or disease-preventing function related to geriatric care for an individual.

[0084] As used herein, the term "dairy product" refers to a food product produced from milk or milk components from animals such as cows, goats, sheep, yaks, horses, camels and other mammals. Examples of dairy products are low-fat milk (e.g., 0.1%, 0.5% or 1.5% fat), skim milk, milk powder, whole milk, whole dairy products, butter, buttermilk, buttermilk products, skimmed milk, skimmed dairy products, high-fat products, condensed milk, whipped cream, cheese, ice cream and confectionery products, probiotic drinks or probiotic yogurt-type drinks.

[0085] The term "dairy product alternative" refers to a product that is similar to a dairy product but is not produced from milk.

[0086] The term "milk" is defined by the Codex Alimentarius Commission as the normal mammary gland secretion of mammals obtained from one or more milkings, without addition or extraction, intended for consumption as liquid milk or for further processing.

[0087] As used herein, the term "beverage product" refers to a nutritional product in liquid or semi-liquid form that can be safely consumed by an individual.

[0088] As used herein, the term "dietary product" refers to a food product that has a restricted and / or reduced calorie content.

[0089] As used herein, the term "pet food product" refers to a nutritional product intended for consumption by a pet. The pets or companion animals mentioned herein should be understood to be animals selected from dogs, cats, birds, fish, rodents (such as mice, rats), etc.

[0090] As used herein, the term "nutritional supplement" refers to a nutritional product that provides an individual with nutrients that the individual may not otherwise consume in sufficient amounts. For example, nutritional supplements can include vitamins, minerals, fiber, fatty acids, or amino acids. Nutritional supplements can be provided, for example, in the form of pills, tablets, lozenges, chewable capsules or tablets, tablets or capsules, or powder supplements that can be, for example, dissolved in water or sprinkled on food. Nutritional supplements typically provide selected nutrients and do not represent a significant proportion of the overall nutritional needs of the subject. Generally, they do not provide more than 0.1%, 1%, 5%, 10%, or 20% of the subject's daily energy requirements. Nutritional supplements can be used during the pre-conception period or during pregnancy or during lactation, for example, as a maternal supplement.

[0091] All of the components of the composition can be mixed together, or alternatively the composition can be provided in the form of a multi-component kit, where the components or groups of components are provided separately. These separate compositions can be intended to be consumed separately or together.

[0092] In a further aspect, the invention relates to a multi-component kit for preventing accelerated growth of offspring, the multi-component kit comprising at least two physically separate compositions each comprising at least one of the above components, wherein at least one of the physically separate compositions comprises myo-inositol and at least one of the physically separate compositions comprises a probiotic.

[0093] In some embodiments, there is provided a multi-component kit for preventing accelerated growth of offspring, the multi-component kit comprising at least two physically separate compositions, each composition comprising at least one component selected from vitamin B2, vitamin B6, vitamin B12, and vitamin D, at least one of the separate compositions comprising myo-inositol and at least one of the separate compositions comprising a combination of Lactobacillus and Bifidobacterium probiotics, wherein the two physically separate compositions are administered to the mother of the offspring during the pre-pregnancy and / or pregnancy and / or lactation periods.

[0094] Each of the physically separate compositions can also comprise one or more of the above components. Suitably, the first composition comprises at least one vitamin selected from vitamin B2, vitamin B6, vitamin B12, vitamin D, and mixtures thereof, and the second composition comprises a probiotic. Myo-inositol can be provided in the first composition or the second composition, or even separately in the first composition or the second composition, but is preferably provided in the composition comprising the vitamins.

[0095] In one embodiment, the multi-component kit contains a first composition and a second composition. The first composition contains myo-inositol and at least one vitamin selected from vitamin B2, vitamin B6, vitamin B12, vitamin D, and mixtures thereof, and optionally further contains the above-mentioned other vitamins and / or nutrients other than probiotics. The second composition contains a combination of Lactobacillus and Bifidobacterium probiotics.

[0096] In another embodiment, the multi-component kit contains a first composition and a second composition. The first composition contains myo-inositol, vitamin B2, vitamin B6, vitamin B12, vitamin D, their mixtures, and zinc. The second composition contains a combination of Lactobacillus and Bifidobacterium probiotics. Due to the presence of high concentrations of minerals or other nutrients, it is preferred to separate the probiotics from other ingredients to avoid any damage to the probiotics.

[0097] Suitably, the compositions or the compositions contained in the multi-component kit can be administered regularly, for example, once a day, twice a day, once every two days, or once a week.

[0098] Those skilled in the art will understand that they can freely combine all the features of the present invention disclosed herein. Specifically, the features described for the products of the present invention can be combined with the methods of the present invention, and vice versa. Additionally, the features described for different embodiments of the present invention can be combined. If there are known equivalents for specific features, such equivalents are incorporated as if they were explicitly mentioned in this specification.

[0099] Based on non-limiting examples, other advantages and features of the present invention will be apparent.

[0100] Those skilled in the art will understand that they can freely combine all the features of the present invention disclosed herein. Specifically, the features described for the products of the present invention can be combined with the methods of the present invention, and vice versa. Additionally, the features described for different embodiments of the present invention can be combined. If there are known equivalents for specific features, such equivalents are incorporated as if they were explicitly mentioned in this specification.

[0101] Based on non-limiting examples, other advantages and features of the present invention will be apparent.

[0102] Example

[0103] Example 1

[0104] A nutritional supplement in powder form intended to be dissolved in water is provided with the ingredients shown in Table 1 below.

[0105] Table 1 - Nutritional supplement

[0106] Ingredient Amount / daily dose Myo - inositol 4g Vitamin D 10 μg Vitamin B6 2.6 mg Vitamin B12 5.2 μg Vitamin B2 1.8 mg Zinc 10 mg β - Carotene 720 μg Folic acid 400 μg Iron 12 μg Calcium 150 μg Iodine 150 μg <![CDATA[Lactobacillus rhamnosus 1) > <![CDATA[1x10 9 cfu]]> <![CDATA[Bifidobacterium lactis BB12 2) > <![CDATA[1x10 9 cfu]]>

[0107] 1) Lactobacillus rhamnosus is deposited as CGMCC 1.3724.

[0108] 2) Bifidobacterium lactis BB12 is deposited as CNCM I-3446.

[0109] The composition is provided in the form of a sachet containing the probiotic as a powder and all other ingredients. Women who desire pregnancy administer the composition during at least one month prior to pregnancy and the woman then continues to administer the composition until parturition.

[0110] Example 2

[0111] Five hundred and eighty-five women (Godfrey KM et al.; Trials (2017), 18:131) participating in the NiPPeR trial at three clinical sites were included in the analysis. This included 295 in the intervention group and 290 in the control group. The mean age of the women was 30 years, at the upper end of the normal weight range and mostly nulliparous. European and Chinese ethnicities accounted for >80% of the ethnicities. Participants were randomly assigned to receive a control nutritional powdered drink rich in standard micronutrients twice daily, or an intervention nutritional powdered drink rich in micronutrients, myo-inositol and probiotics (i.e., the composition according to the invention) twice daily. Women who became pregnant within the first year of starting the nutritional powdered drink were followed throughout pregnancy and their offspring were studied during the first two years of life.

[0112] The nutritional intervention significantly reduced the risk, statistically, of accelerated growth (weight z-score / year increase >0.67 by age) from birth to 1 year and from birth to 2 years in the offspring of mothers receiving the composition according to the invention. As observed in Table 2, 21.9% of the infants in the intervention experienced accelerated growth from birth to 1 year, compared to 31.1% in the control group. This resulted in an adjusted risk ratio (aRR) of 0.76 for the offspring of women receiving the intervention, equivalent to a 24% reduction in the risk observed in the offspring of control women. Similarly, 7.7% of the offspring of women receiving the intervention experienced accelerated growth from birth to 2 years, compared to 17.1% in the control group. In the case where the aRR is 0.55, the risk of experiencing accelerated growth during this time span is reduced by 45%.

[0113] Table 2 - Adjusted risk ratio (aRR) and 95% confidence interval (CI) for rapid weight gain from birth to 1 year and 2 years (confidence interval, CI)

[0114]

[0115] The data are aRR and their respective 95% CIs derived from logistic regression adjusted for study site (UK / Singapore / New Zealand), infant sex (male / female), parity (nulliparous / multiparous), maternal smoking (none / active / passive), maternal pre-pregnancy BMI, age at visit, and gestational age at birth. Statistically significant comparisons (p>0.05) are shown in bold.

[0116] Example 3

[0117] Accelerated growth during the first two years of life is associated with a greater risk of obesity during childhood and adulthood (Druet C (2012) Paediatric and perinatal epidemiology 26.1:19-26). Nutritional intervention led to a statistically significant reduction in the risk of obesity at 2 years of age in the offspring of mothers receiving the composition according to the invention (i.e., the intervention), as defined by having a BMI > 95th percentile (BMI > 1.65), as described in Table 3.

[0118] Table 3 - Adjusted risk ratio (aRR) and 95% confidence interval (CI) for rapid weight gain from birth to 1 year and 2 years

[0119] BMI SDS n / N Intervention vs. control aRR 95% CI p - value >1.65 66 / 484 22 [9.2%] vs. 44 [18.0%] 0.51 0.31、0.82 0.006

[0120] The data are aRR and their respective 95% CIs derived from logistic regression adjusted for study site, infant sex, parity (nulliparous / multiparous), maternal smoking during pregnancy (none / active / passive), maternal pre-pregnancy BMI, and gestational age at birth.

[0121] Example 4: Rapid weight gain and percentage of body fat increase (FM%)

[0122] From Example 3, maternal intervention was associated with a lower incidence of rapid weight gain (from birth to 1 year > 0.67SD; from birth to 2 years > 1.34SD). Early rapid weight gain is associated with a later risk of obesity. (Zheng M, et al. Obes Rev. 2018;19(3):321-32). Therefore, we also evaluated potential differences in body composition between children who experienced rapid weight gain and those who did not, regardless of the treatment their mothers received (i.e., adjusted for group and other factors). Similarly, we explored differences in body composition between obese children (BMI > 95th percentile) and non-obese children (BMI ≤ 95th percentile) at 2 years of age.

[0123] Method

[0124] Anthropometry: Birth weight was collected from hospital records, and subsequent weight measurements were made to the nearest 1 g up to 1 year of age. At 2 years of age, weight was measured to the nearest 0.1 kg. Crown-heel length was measured up to 1 year of age using a neonatometer or infantometer. Standing height was measured using a stadiometer at 2 years of age.

[0125] Bioelectrical impedance spectroscopy (BIS) measurements were performed at 6 weeks, 6 months, 1 year, and 2 years of age. Measurements were made using an ImpediMed SFB7 device (ImpediMed, Brisbane, Australia).

[0126] We used PEAPOD measurements and prediction equations specific to our cohort at 6 weeks and 6 months (Lyons-Reid J et al. Prediction of fat-free mass in a multi-ethnic cohort of infants using bioelectrical impedance: Validation against the PEAPOD. Frontiers in Nutrition. 2022;9:980790):

[0127] 6-week-old males: FFM = 0.23 + 0.65W + 0.10L 2 / R 50

[0128] 6-week-old females: FFM = 0.60 + 0.58W + 0.08L 2 / R 50

[0129] 6-month-old males: FFM = 1.26 + 0.46W + 0.14L 2 / R 50

[0130] 6-month-old females: FFM = 1.40 + 0.36W + 0.21L 2 / R 50

[0131] Abbreviations: W, weight (kg); L, length (cm); R 50 , resistance at 50 kHz.

[0132] FM (kg) was calculated as the difference between the measured weight and the estimated FFM, and subsequently the percentage of fat mass (FM%) was calculated:

[0133] FM = W - FFM

[0134] FM% = (FM / (FM + FFM)) * 100

[0135] At 1 and 2 years of age, the same 6 - month equation is used.

[0136] Result

[0137] Data on rapid weight gain from birth to 1 year and birth to 2 years are shown in Table 2.

[0138] Regardless of the intervention effect, those who develop rapid weight gain (>0.67 SD) during the first year of life had similar body composition at 6 weeks, but higher FM% at 6 months, 1 year, and 2 years (+2.0, +2.0, and +1.4 percentage points respectively) compared to those who did not experience rapid weight gain. Children who experienced rapid weight gain >1.34 SD from birth to 2 years had lower FM% at 6 weeks (-0.9 percentage points), but increased FM% at subsequent visits (+1.4, +1.9, and +1.7 percentage points respectively).

[0139] The results showed that regardless of the intervention effect, children who experienced rapid weight gain in infancy or early childhood or high BMI at 2 years of age developed higher levels of obesity (FM%). In summary, Examples 3 and 4 showed that more control group children experienced rapid weight gain and high BMI, characterized by higher FM%.

[0140] In summary, the intervention was associated with a reduced incidence of rapid weight gain in infancy and early childhood and high BMI at 2 years of age. Since children in these high - risk subgroups had higher levels of obesity, nutritional intervention could reduce the risk of experiencing excess fat mass.

Claims

1. A composition for preventing accelerated growth in offspring, the composition comprising a combination of Lactobacillus and Bifidobacterium probiotics, inositol, and at least one vitamin selected from vitamin B2, vitamin B6, vitamin B12, vitamin D, and mixtures thereof, and wherein the composition is administered to the mother of the offspring during preconception and / or pregnancy and / or lactation.

2. The composition for the use according to claim 1, the composition reducing the risk of experiencing an excessive amount of fat in subsequent life.

3. The composition for the use according to any one of claims 1 or 2, wherein the Lactobacillus is a strain of Lactobacillus rhamnosus obtainable under deposit number CGMCC 1.3724, and the Bifidobacterium is a strain of Bifidobacterium lactis BB12 deposited as CNCM I-3446.

4. The composition for the use according to any one of the preceding claims, wherein the accelerated growth occurs during the first 2 to 5 years of the life of the offspring.

5. The composition for the use according to any one of the preceding claims, wherein the composition comprises inositol, vitamin B2, vitamin B6, vitamin B12, vitamin D, and a combination of Lactobacillus rhamnosus CGMCC 1.3724 and Bifidobacterium lactis BB12 CNCM I-3446.

6. A composition for the use according to any one of the preceding claims, wherein the composition comprises 0.2 g to 5 g of myo-inositol, 0.14 mg to 14 mg of vitamin B2, 0.19 mg to 19 mg of vitamin B6, 0.26 μg to 26 μg of vitamin B12, 1.5 μg to 100 μg of vitamin D, 10 5 cfu to 10 12 cfu of Lactobacillus rhamnosus CGMCC 1.3724 and 10 5 cfu to 10 12 cfu of Bifidobacterium lactis BB12 CNCM I-3446, all amounts being defined by the daily dose.

7. The composition for the use according to any one of the preceding claims, wherein the composition further comprises zinc.

8. The composition for the use according to claim 6, wherein the composition comprises zinc in an amount of from 1.1 mg to 40 mg per daily dose.

9. The composition for the use according to any one of the preceding claims, wherein the composition further prevents the development of metabolic disorders in the offspring in subsequent life by preventing the accelerated growth.

10. The composition for the use according to any one of the preceding claims, wherein the metabolic disorder is a cardio-metabolic disorder, obesity, excessive fat mass accumulation, and / or overweight.

11. The composition for the use according to any one of the preceding claims, wherein the mother of the offspring is a mammal, such as a mammal selected from cats, dogs, and humans.

12. The composition for the use according to any one of the preceding claims, wherein the composition is for administration to the mother of the offspring during pregnancy, such as during the entire second and third trimesters of pregnancy.

13. The composition for the use according to any one of the preceding claims, wherein the composition is in the form of a powdered nutritional composition, food product, drink, nutritional supplement, or nutraceutical for reconstitution in milk or water.

14. A multi-component kit for preventing accelerated growth in offspring, the multi-component kit containing at least two physically separated compositions, each composition containing at least one ingredient selected from riboflavin, vitamin B6, vitamin B12, and vitamin D, at least one of the separated compositions containing myo-inositol and at least one of the separated compositions containing a combination of Lactobacillus and Bifidobacterium probiotics, wherein the two physically separated compositions are administered to the mother of the offspring during the pre-pregnancy and / or pregnancy and / or lactation period.

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