Nutritional composition, product comprising same and use thereof

Abstract

The present invention relates to nutritional compositions, products comprising them and uses thereof. The nutritional composition comprises partially hydrolyzed proteins and medium and long chain fatty acid triglycerides. The nutritional composition has a synergistic effect on improving intestinal health, especially inhibiting staphylococcus aureus and / or improving diarrhea. The invention also relates to the use of said nutritional composition in the preparation of a product for improving intestinal health.

Description

Technical Field

[0001] This disclosure relates to the field of food technology, and in particular to nutritional compositions, products containing the same, and their uses. Background Technology

[0002] Diarrhea is a common and prevalent gastrointestinal disease, among which infectious diarrhea is particularly prominent due to its high transmissibility and incidence, posing a serious challenge to global public health systems for a long time. Children, whose immune and digestive systems are not yet fully developed, have a significantly higher incidence and risk of transmission of infectious diarrhea than adults, which not only seriously affects their healthy development but is also a major contributing factor to childhood malnutrition.

[0003] From an etiological perspective, infectious diarrhea is mainly caused by a variety of pathogens, including bacteria, viruses, fungi, and parasites, and is a typical intestinal infectious disease. Among them, Staphylococcus aureus is an important zoonotic pathogen with a high carrier rate in both humans and livestock. This bacterium can cause a variety of diseases ranging from mild to severe, including skin infections, pneumonia, sepsis, and infectious diarrhea. Staphylococcus aureus induces intestinal inflammatory responses by producing various virulence factors (such as enterotoxins and hemolysins), disrupting the intestinal mucosal barrier function, thereby leading to diarrheal symptoms. At the same time, the problem of drug resistance in this bacterium is becoming increasingly prominent. The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has made clinical treatment more complex, and the current lack of an effective vaccine further exacerbates the difficulty of prevention and control.

[0004] Gut health is a crucial foundation for maintaining normal physiological functions. It is not only closely related to nutrient digestion and absorption, but also participates in the body's immune defense through the gut microbiota, intestinal mucosal barrier, and gut-associated immune system. When the gut microbiota is imbalanced or the intestinal barrier is damaged, it can easily induce diarrhea and intestinal inflammation, with particularly significant harm in susceptible populations.

[0005] Currently, Staphylococcus aureus infection and the resulting diarrhea are mainly treated with antibiotics. However, long-term or inappropriate use of antibiotics can easily induce the development of drug-resistant strains and may also cause intestinal flora imbalance and various adverse reactions, limiting their application in long-term conditioning and prevention. In this context, developing safe, effective, and regulatory alternative or adjunctive interventions has become an important research direction in this field.

[0006] Therefore, there remains a need in the art for methods that can improve gut health, particularly by inhibiting Staphylococcus aureus and / or by improving diarrhea. Summary of the Invention

[0007] This invention was made in view of the above-mentioned problems existing in the prior art.

[0008] The first aspect of the present invention provides a nutritional composition comprising partially hydrolyzed protein and medium- and long-chain fatty acid triglycerides.

[0009] The applicant found that when the nutritional composition contains partially hydrolyzed protein and medium- and long-chain fatty acid triglycerides, there is a synergistic effect between the two in improving gut health, particularly in inhibiting Staphylococcus aureus and improving diarrhea.

[0010] A second aspect of the present invention provides a product comprising the nutritional composition described in the first aspect of the present invention.

[0011] A third aspect of the present invention provides the use of a nutritional composition according to the first aspect of the present invention in the preparation of a product for improving gut health. Attached Figure Description

[0012] Figure 1 This is a statistical graph of the fluorescence intensity in the intestines of zebrafish after sample treatment. The graph shows the fluorescence intensity compared to the model control group. This indicates that p < 0.05. This indicates that p < 0.01. ! indicates p < 0.001; compared with Comparative Example 1, ! indicates p < 0.05, !! indicates p < 0.01; compared with Comparative Example 2, @@@ indicates p < 0.001; compared with Comparative Example 3, ## indicates p < 0.01, ### indicates p < 0.001; compared with Comparative Example 4, $ indicates p < 0.05, $$ indicates p < 0.001; compared with Comparative Example 5, %% indicates p < 0.01, %%% indicates p < 0.001.

[0013] Figure 2 This is a typical image of the fluorescence intensity in the zebrafish intestine after sample treatment.

[0014] Figure 3 This is a statistical graph showing the fluorescence intensity of Staphylococcus aureus in the intestine of zebrafish after sample treatment, with comparisons made with the model control group. This indicates that p < 0.05. This indicates that p < 0.01. !! indicates p < 0.001; compared with Comparative Example 1, !! indicates p < 0.01, !!! indicates p < 0.001; compared with Comparative Example 2, @ indicates p < 0.05, @@@ indicates p < 0.001; compared with Comparative Example 3, ## indicates p < 0.01, ### indicates p < 0.001; compared with Comparative Example 4, $$ indicates p < 0.01; compared with Comparative Example 5, %% indicates p < 0.01, %%% indicates p < 0.001.

[0015] Figure 4 This is a typical image showing the fluorescence intensity of Staphylococcus aureus in the intestine of zebrafish after sample treatment. Detailed Implementation

[0016] The following definitions are provided to enable those skilled in the art to understand the invention. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Preferred materials and methods are described herein, but any methods and materials similar to or equivalent to those described herein may be used in the practice of testing the invention. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0017] Unless otherwise indicated or defined, all terms used have their ordinary meaning in the art as would be understood by those skilled in the art. Furthermore, unless otherwise stated, all methods, steps, techniques, and operations not specifically detailed herein may be performed and have been carried out in a manner known per se as would be understood by those skilled in the art.

[0018] The present invention will be described in detail below.

[0019] Nutritional composition

[0020] The first aspect of the present invention provides a nutritional composition comprising partially hydrolyzed protein and medium- and long-chain fatty acid triglycerides.

[0021] The applicant found that when the nutritional composition contains partially hydrolyzed protein and medium- and long-chain fatty acid triglycerides, there is a synergistic effect between the two in improving gut health, particularly in inhibiting Staphylococcus aureus and improving diarrhea.

[0022] In some embodiments, the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein in the nutritional composition is 0.1-40; within this range, the synergistic effect of the medium- and long-chain fatty acid triglycerides and the partially hydrolyzed protein in inhibiting Staphylococcus aureus and improving diarrhea is more significant. For example, the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein in the nutritional composition is within the range defined by any two of the following: 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40.

[0023] In some embodiments, the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein in the nutritional composition is 0.1-10; within this range, the synergistic effect of the medium- and long-chain fatty acid triglycerides and the partially hydrolyzed protein in inhibiting Staphylococcus aureus and improving diarrhea is more significant.

[0024] In some embodiments, the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein in the nutritional composition is 0.1-8; within this range, the synergistic effect of the medium- and long-chain fatty acid triglycerides and the partially hydrolyzed protein in inhibiting Staphylococcus aureus and improving diarrhea is more significant.

[0025] In some embodiments, the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein in the nutritional composition is 0.4-8; within this range, the synergistic effect of the medium- and long-chain fatty acid triglycerides and the partially hydrolyzed protein in inhibiting Staphylococcus aureus and improving diarrhea is more significant.

[0026] In some embodiments, the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein in the nutritional composition is 0.4-2; within this range, the synergistic effect of the medium- and long-chain fatty acid triglycerides and the partially hydrolyzed protein in inhibiting Staphylococcus aureus and improving diarrhea is more significant.

[0027] In some embodiments, the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein in the nutritional composition is 0.4-1.6; within this range, the synergistic effect of the medium- and long-chain fatty acid triglycerides and the partially hydrolyzed protein in inhibiting Staphylococcus aureus and improving diarrhea is more significant.

[0028] As used herein, the term "partially hydrolyzed protein" refers to a product obtained by partially hydrolyzing a protein, to a degree less than that of complete hydrolysis. The partially hydrolyzed protein may comprise a mixture of protein fragments, polypeptides, peptides, amino acids, and / or peptones. It should be understood that partial hydrolysis does not include products obtained from complete hydrolysis of a protein consisting solely of free amino acids.

[0029] The hydrolysis process can be, for example, acid hydrolysis, alkaline hydrolysis, and / or enzymatic hydrolysis, with enzymatic hydrolysis being preferred. Unbound by any theoretical constraints, enzymatic hydrolysis offers higher selectivity at cleavage sites on protein molecules compared to acid or alkaline hydrolysis, thereby yielding protein fragments and peptides with more controllable molecular weight distribution and more stable functional properties.

[0030] The partially hydrolyzed protein may be a partially hydrolyzed animal protein and / or a partially hydrolyzed plant protein. In some embodiments, the partially hydrolyzed protein is a partially hydrolyzed plant protein selected from one or more of soy protein, pea protein, wheat protein, and rice protein. In some embodiments, the partially hydrolyzed protein is a partially hydrolyzed animal protein, such as partially hydrolyzed milk protein (i.e., partially hydrolyzed cow's milk protein), selected from whey protein, casein, or mixtures thereof, preferably whey protein. Preferably, the partially hydrolyzed protein is derived from demineralized whey powder.

[0031] In some embodiments, the degree of hydrolysis of the partially hydrolyzed protein may be 7%-25%; within this range, the nutritional composition is more effective in improving gut health, such as inhibiting Staphylococcus aureus and / or improving diarrhea. The degree of hydrolysis of the partially hydrolyzed protein may be, for example, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, or within the range defined by any two thereof. Preferably, the degree of hydrolysis of the partially hydrolyzed protein is 7%-17%; within this range, the nutritional composition is more effective in improving gut health, such as inhibiting Staphylococcus aureus and / or improving diarrhea. Preferably, the degree of hydrolysis of the partially hydrolyzed protein is 7%-15%; within this range, the nutritional composition is more effective in improving gut health, such as inhibiting Staphylococcus aureus and / or improving diarrhea.

[0032] In some embodiments, peptides with a molecular weight >5000 Da constitute 10%-80% of the mass of the partially hydrolyzed protein; within this range, the nutritional composition is more effective in improving gut health, such as inhibiting Staphylococcus aureus and / or improving diarrhea. In the partially hydrolyzed protein, the proportion of peptides with a molecular weight >5000 Da is, for example, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, or within the range defined by any two of these. Preferably, in the partially hydrolyzed protein, peptides with a molecular weight >5000 Da account for 10%-70% by mass; within this range, the nutritional composition is more effective in improving gut health, such as inhibiting Staphylococcus aureus and / or improving diarrhea.

[0033] In some embodiments, the proportion of peptides with a molecular weight of 1000-5000 Da in the partially hydrolyzed protein is 7%-47% by mass; within this range, the nutritional composition is more effective in improving gut health, such as inhibiting Staphylococcus aureus and / or improving diarrhea. The proportion of peptides with a molecular weight of 1000-5000 Da in the partially hydrolyzed protein is, for example, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, or within the range defined by any two of these. Preferably, in the partially hydrolyzed protein, peptides with a molecular weight of 1000-5000 Da account for 10%-35% by mass; within this range, the nutritional composition is more effective in improving gut health, such as inhibiting Staphylococcus aureus and / or improving diarrhea.

[0034] In some embodiments, peptides with a molecular weight <1000 Da account for 13%-80% of the mass of the partially hydrolyzed protein; within this range, the nutritional composition is more effective in improving gut health, such as inhibiting Staphylococcus aureus and / or improving diarrhea. In the partially hydrolyzed protein, the proportion of peptides with a molecular weight <1000 Da is, for example, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, or within the range defined by any two of these. Preferably, in the partially hydrolyzed protein, peptides with a molecular weight <1000 Da account for 15%-58% by mass; within this range, the nutritional composition is more effective in improving gut health, such as inhibiting Staphylococcus aureus and / or improving diarrhea.

[0035] In some preferred embodiments, the degree of hydrolysis of the partially hydrolyzed protein is 7%-15%, the proportion of peptides with a molecular weight >5000 Da is 10%-70% by mass, the proportion of peptides with a molecular weight of 1000-5000 Da is 10%-35% by mass, and the proportion of peptides with a molecular weight <1000 Da is 15%-58% by mass; within this range, the nutritional composition is more effective in improving gut health, such as inhibiting Staphylococcus aureus and / or improving diarrhea.

[0036] The partially hydrolyzed protein may be a single partially hydrolyzed protein or a mixture of two or more partially hydrolyzed proteins.

[0037] In this application, the term "medium-chain fatty acid" refers to fatty acids with 6-12 carbon atoms in their carbon chain, such as hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, and dodecanoic acid. The term "long-chain fatty acid" refers to fatty acids with 14 or more carbon atoms in their carbon chain, generally 14-30 carbon atoms, such as myristic acid, palmitic acid, oleic acid, linoleic acid, stearic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. The terms "medium-chain fatty acid triglyceride" and "long-chain fatty acid triglyceride" refer to the esterification products of "medium-chain fatty acids" and "long-chain fatty acids" with glycerol, respectively.

[0038] As used herein, the term "medium- and long-chain triglycerides" (MLCT) refers to a class of triglycerides that contain both medium-chain and long-chain fatty acid residues in their molecular structure. MLCTs possess different physicochemical properties, metabolic characteristics, and nutritional value from long-chain triglycerides (LCT) or medium-chain triglycerides (MCT). Studies (see, for example, Yuan Tinglan, Composition and Metabolic Characteristics of Medium- and Long-Chain Triglycerides in Breast Milk Fat [D], Jiangnan University, 2021) show that medium- and long-chain triglycerides (MLCT) are not simply equivalent to a physical mixture of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) (nor are they simply equivalent to a mixture of long-chain and medium-chain fatty acids), and the latter does not possess the physicochemical properties, metabolic characteristics, and nutritional value of the former.

[0039] According to the relevant provisions of the "Administrative Measures for New Resource Foods", MLCT is made from edible vegetable oil and medium-chain triglycerides as raw materials, through lipase transesterification reaction, and then through processes such as distillation separation, decolorization, and deodorization.

[0040] This invention does not have any particular requirements for the MLCT used; any MLCT commonly used in the art can be used. MLCT can be used in pure form or in an impure form rich in MLCT. The MLCT component contained in the nutritional composition can be a single-component MLCT (i.e., each molecular chain has the same long-chain fatty acid residues and the same medium-chain fatty acid residues) or a mixture of two or more different-component MLCTs (i.e., each molecular chain has different long-chain fatty acid residues and / or different medium-chain fatty acid residues).

[0041] In some embodiments, the MLCT used in this invention comprises C6-C 12( For example, C6, C7, C8, C9, C 10 C 11 C 12 (or the range defined by either or both) fatty acid residues and C 14 -C 30 (e.g., C) 14 C 15 C 16 C 17 C 18 C 19 C 20 C 21 C 22 C 23 C 24 C 25 C 26 C 27 C 28 C 29C 30 (or the range defined by either or both) fatty acid residues. The C6-C 12 The fatty acid residues may be derived from one or more of the following: hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, etc., preferably hexanoic acid, octanoic acid, decanoic acid, and lauric acid. The C 14 -C 30 The fatty acid residues may be derived from one or more of the following: myristic acid, palmitic acid, heptadecanic acid, oleic acid, linoleic acid, stearic acid, nonadecanic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapatraenoic acid, docosahexaenoic acid, tricarboxylic acid, docosapetraenoic acid, docosapatraenoic acid, docosahexaenoic acid, arachidonic acid, etc., preferably myristic acid, palmitic acid, oleic acid, linoleic acid, stearic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapatraenoic acid and docosahexaenoic acid.

[0042] In some embodiments, the C6-C in the MLCT 12 Fatty acid residues on the C 14 -C 30 The weight ratio of fatty acid residues is from 0.124 to 2.000. As an example, the C6-C... 12 Fatty acid residues on the C 14 -C 30 The weight ratio of fatty acid residues may be 0.124, 0.125, 0.130, 0.140, 0.150, 0.160, 0.170, 0.180, 0.190, 0.200, 0.300, 0.400, 0.500, 0.600, 0.700, 0.800, 0.900, 1.000, 1.100, 1.200, 1.300, 1.400, 1.500, 1.600, 1.700, 1.800, 1.900, 2.000, or within the range defined by any two of these.

[0043] As used in this article, *Staphylococcus aureus*, also known as "S. aureus," belongs to the genus *Staphylococcus* and is a representative Gram-positive bacterium. It is a common foodborne pathogen widely found in the natural environment. Under suitable conditions, *Staphylococcus aureus* can produce enterotoxins, causing food poisoning. Enterotoxins are single-chain small protein molecules with a molecular weight of approximately 26-29 kDa. They have a relatively low molecular weight, are heat-stable, and damage the human intestines, leading to symptoms such as vomiting and diarrhea.

[0044] In some embodiments, inhibiting Staphylococcus aureus includes inhibiting Staphylococcus aureus in vivo or in vitro. In some embodiments, inhibiting Staphylococcus aureus includes inhibiting infections caused by Staphylococcus aureus in vivo or in vitro. In some embodiments, the infections include purulent inflammation, enteritis, diarrhea, etc. In some embodiments, the inhibition includes inhibiting the growth, proliferation, or production of metabolites of Staphylococcus aureus.

[0045] product

[0046] A second aspect of the present invention provides a product comprising the nutritional composition described in the first aspect of the present invention.

[0047] All descriptions above relating to the first aspect of the present invention are applicable here and will not be repeated here.

[0048] In some embodiments, the product is food or medicine, for example, food.

[0049] In some embodiments, the food is, for example, a functional food, a health food, or a health supplement. In some embodiments, the food is a general food or a specialty food. In some embodiments, the food may be a granular powder, tablet, or liquid. In some embodiments, the food is selected from dairy products, confectionery, beverages, fermented foods, bread, and biscuits, such as dairy products. In some embodiments, the dairy product is selected from milk powder, modified milk powder, formula powder, or solid beverages.

[0050] In some embodiments, the nutritional composition according to the first aspect of the invention is added to dairy products as a beneficial ingredient.

[0051] Furthermore, those skilled in the art will readily understand that, in addition to the nutritional composition of the first aspect of the present invention, the food may also include one or more of the following: raw milk, demineralized whey powder, whey protein concentrate, lactose, blended vegetable oil, fructooligosaccharides, galactooligosaccharides, nucleotides, choline, vitamins, minerals, DHA, and taurine.

[0052] For example, when the food is milk powder, in addition to the nutritional composition described in the first aspect of the present invention, the milk powder may also include proteins such as α-lactalbumin and milk fat globule membrane protein; carbohydrates such as lactose; lipids; minerals such as calcium, iron, and phosphorus; vitamins; and other additives such as whey powder, choline tartrate, docosahexaenoic acid, arachidonic acid, and walnut oil.

[0053] In some embodiments, the drug may be any dosage form, such as a solid dosage form (granules, powders, tablets, etc.) or a liquid dosage form. Furthermore, those skilled in the art will readily understand that, depending on the dosage form and application scenario, the drug may also include various pharmaceutically permissible excipients.

[0054] The products, such as food and pharmaceuticals, can be prepared using methods commonly employed in the art, which will not be elaborated upon here.

[0055] In some embodiments, the content of the partially hydrolyzed protein in the product is 0.1%-50% based on the total dry weight of the product (after deducting moisture). As an example, based on the total dry weight of the product, the content of the partially hydrolyzed protein in the product is within the range defined by 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, or any two of these.

[0056] In some embodiments, the content of medium- and long-chain fatty acid triglycerides in the product is 0.1%-30% based on the total dry weight of the product (after deducting moisture). As an example, the content of medium- and long-chain fatty acid triglycerides in the product is within the range defined by any two of the following, based on the total dry weight of the product: 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%.

[0057] use

[0058] A third aspect of the present invention provides the use of a nutritional composition according to the first aspect of the present invention in the preparation of a product for improving gut health.

[0059] In some embodiments, improving gut health includes improving diarrhea. In some embodiments, improving gut health includes inhibiting Staphylococcus aureus. In some embodiments, improving gut health includes both inhibiting Staphylococcus aureus and improving diarrhea. In some embodiments, the diarrhea is diarrhea caused by Staphylococcus aureus. In some embodiments, inhibiting Staphylococcus aureus includes inhibiting the growth, proliferation, or production of metabolites of Staphylococcus aureus.

[0060] All of the above descriptions regarding the first and second aspects of the present invention are applicable herein and will not be repeated here.

[0061] In some embodiments, the subjects for improving intestinal health are not particularly limited and may include, for example, infants, toddlers, children, juveniles, adults, young people, middle-aged people, and / or the elderly.

[0062] As used herein, the following terms have the following meanings.

[0063] The term "infant" refers to a person from birth to 12 months of age.

[0064] The term "toddler" refers to a person from the age of 1 to 3 years.

[0065] The term "child" refers to a person from the age of 3 to 7 years.

[0066] The term "juvenile" refers to a person from the age of 7 to 17 years.

[0067] The term "adult" refers to a person over 18 years of age.

[0068] The term "young person" refers to a person from the age of 18 to 40 years.

[0069] The term "middle-aged person" refers to a person from the age of 41 to 65 years.

[0070] The term "elderly person" or "the elderly" refers to a person over 65 years of age.

[0071] Examples

[0072] The present invention will be more easily understood by referring to the following examples, which are only used to illustrate some aspects and embodiments of the present invention and are not intended to limit the present invention.

[0073] Unless otherwise specified, the materials used in this example are all commercially available materials or conventional materials.

[0074] Experimental animals and bacteria

[0075] Zebrafish were all raised in fish culture water at 28 °C (water quality: 200 mg of instant sea salt was added to every 1 L of reverse osmosis water, the conductivity was 450 - 550 μS / cm; the pH was 6.5 - 8.5; the hardness was 50 - 100 mg / L CaCO3), provided by the fish culture center of Huante Biotechnology Co., Ltd. The license number for the use of experimental animals was: SYXK(Zhe)2022 - 0004, and the feeding management complied with the requirements of international AAALAC certification (certification number: 001458), and the IACUC ethical review number was: IACUC - 2025 - 202510290010 - 01.

[0076] Staphylococcus aureus, nutrient broth medium, cultured at 37°C.

[0077] Instruments, consumables and reagents

[0078] Motorized focusing continuous zoom fluorescence microscope (AZ100, Nikon, Japan).

[0079] The medium- and long-chain fatty acid triglycerides were derived from medium- and long-chain fatty acid edible oil (production batch number 20250804) supplied by Yihai Kerry, with a purity of 61%.

[0080] The hydrolyzed protein is a partially hydrolyzed whey protein derived from Hilmar PROtelyzeAdvance (with a degree of hydrolysis in the range of 7%-15%) provided by Galaxy Ventures.

[0081] Vancomycin, white powder, batch number C12976208, Shanghai Maclean Biochemical Technology Co., Ltd., solvent is DMSO;

[0082] Nutrient broth culture medium (batch number 1094671, Huankai Microbial Technology Co., Ltd., China);

[0083] Dimethyl sulfoxide (DMSO, batch number 20250624, Sinopharm Chemical Reagent Co., Ltd., China);

[0084] Nile Red (lot number SLBP9326V, Sigma, India); CM-DiI (lot number 2335589, Thermo Fisher Scientific (China) Co., Ltd., USA).

[0085] Evaluation of the efficacy of the sample in improving diarrhea

[0086] Wild-type AB strain zebrafish with a dpf of 4 were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). Water-soluble samples (concentrations shown in Table 1) were used as examples / comparative examples. Vancomycin at a concentration of 1000 μg / mL was used as a positive control. Normal and model control groups were also included, with a volume of 3 mL per well. After treatment at 28℃ for 5 h, Nile red was added as a fluorescent indicator of intestinal contents in each experimental group. Treatment continued at 28℃ for 16 h, after which the samples and Nile red were washed away, and water-soluble samples were added again (concentrations shown in Table 1). Except for the normal control group, the remaining experimental groups were given Staphylococcus aureus in water to establish a zebrafish diarrhea model. After treatment continued at 28℃ for 30 h, 10 zebrafish were randomly selected from each experimental group and photographed under a fluorescence microscope. Data were analyzed and collected using NIS-Elements D 3.20 advanced image processing software. The fluorescence intensity of the zebrafish intestine was analyzed, and the statistical analysis results were used to evaluate the efficacy of the samples in improving Staphylococcus aureus-induced diarrhea. Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software, and p < 0.05 was considered statistically significant.

[0087] Then, for each embodiment and comparative example, the increase in intestinal fluorescence intensity compared to the model control group was calculated (denoted as C), and for each embodiment, the sum of the increases in intestinal fluorescence intensity compared to the model control group for the corresponding comparative example was calculated (denoted as D). For example, for Example 1 (partially hydrolyzed protein concentration 3.12 μg / mL + MLCT concentration 5 μg / mL), the "sum of increases in intestinal fluorescence intensity compared to the model control group for the corresponding comparative example" is the sum of the "increases in intestinal fluorescence intensity compared to the model control group" for Comparative Example 1 (MLCT 5 μg / mL) and Comparative Example 4 (partially hydrolyzed protein 3.12 μg / mL). Finally, based on the partially hydrolyzed protein concentration (denoted as A) and the MLCT concentration (denoted as B), the unit dose contribution value (denoted as E, E=C / (A+B)) was calculated. When C>D, it indicates a synergistic effect; the larger the E value, the stronger the synergistic effect.

[0088] Following the above method, zebrafish were administered medium- and long-chain triglycerides and partially hydrolyzed proteins at different ratios to evaluate their efficacy in improving diarrhea. The dosages are shown in Table 1. The results are also shown in Table 1. Figure 1 and Figure 2 As shown.

[0089] Table 1. Experimental results evaluating the efficacy of the samples in improving diarrhea (n = 10)

[0090]

[0091] Note: Compared with the model control group, This indicates that p < 0.05. This indicates that p < 0.01. This indicates that p < 0.001;

[0092] Compared with Comparative Example 1, ! indicates p < 0.05, and !! indicates p < 0.01;

[0093] Compared with Comparative Example 2, @@@ indicates p < 0.001;

[0094] Compared with Comparative Example 3, ## indicates p < 0.01, and ### indicates p < 0.001;

[0095] Compared with Comparative Example 4, $ indicates p < 0.05, and $$ indicates p < 0.001;

[0096] Compared with Comparative Example 5, %% indicates p < 0.01, and %%% indicates p < 0.001.

[0097] From Table 1, Figure 1 and Figure 2 The results showed that the positive control drug (vancomycin, 1000 μg / mL), single-component partially hydrolyzed protein (12.5 μg / mL and 50 μg / mL), single-component MLCT (125 μg / mL) and Examples 1-7 all had significant effects in improving diarrhea, specifically, compared with the model control, their intestinal fluorescence intensity (pixels) was significantly increased (P<0.05).

[0098] Example 1 (MLCT to partially hydrolyzed protein weight ratio of 1.6) is equivalent to a combination of Comparative Example 1 (MLCT 5 µg / mL) and Comparative Example 4 (single-component partially hydrolyzed protein 3.12 µg / mL). Compared with the model control group, Example 1 showed an increase of 43051 in intestinal fluorescence intensity (pixels), while Comparative Examples 1 and 4 showed increases of 7465 and 28764, respectively. The former was greater than the sum of the latter two (36229), indicating a synergistic effect of Example 1 in improving diarrhea. Similarly, Examples 2-7 also showed a synergistic effect in improving diarrhea.

[0099] Furthermore, Examples 1-5 and 7 (MLCT to partially hydrolyzed protein weight ratio of 0.1-10) had a larger unit dose contribution value (i.e. E value) compared to Example 6 (MLCT to partially hydrolyzed protein weight ratio of 40), indicating that the synergistic effect of MLCT and partially hydrolyzed protein in improving diarrhea was more significant at this weight ratio.

[0100] Furthermore, Examples 1-5 (MLCT to partially hydrolyzed protein weight ratio of 0.1-8) showed a greater contribution per unit dose compared to Examples 6 and 7 (MLCT to partially hydrolyzed protein weight ratios of 40 and 10, respectively), indicating that the synergistic effect of MLCT and partially hydrolyzed protein in improving diarrhea was more significant at this weight ratio.

[0101] Furthermore, Examples 1, 2, 4, and 5 (MLCT to partially hydrolyzed protein weight ratio of 0.4-8) showed a greater contribution per unit dose compared to Examples 3, 6, and 7 (MLCT to partially hydrolyzed protein weight ratios of 0.1, 40, and 10, respectively), indicating that the synergistic effect of MLCT and partially hydrolyzed protein in improving diarrhea was more significant at this weight ratio.

[0102] Furthermore, Examples 1, 2, and 5 (MLCT to partially hydrolyzed protein weight ratio of 0.4-2) showed a greater contribution per unit dose compared to Examples 3, 4, 6, and 7 (MLCT to partially hydrolyzed protein weight ratios of 0.1, 8, 40, and 10, respectively), indicating that the synergistic effect of MLCT and partially hydrolyzed protein in improving diarrhea was more significant at this weight ratio.

[0103] Furthermore, Examples 1 and 2 (MLCT to partially hydrolyzed protein weight ratio of 0.4-1.6) showed a greater contribution per unit dose compared to Examples 3-7 (MLCT to partially hydrolyzed protein weight ratios of 0.1, 8, 2, 40 and 10, respectively), indicating that the synergistic effect of MLCT and partially hydrolyzed protein in improving diarrhea was more significant at this weight ratio.

[0104] Evaluation of the efficacy of the sample in inhibiting Staphylococcus aureus

[0105] Wild-type AB strain zebrafish (4 dpf) were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). Water-soluble samples (concentrations shown in Table 2) were administered, along with a positive control of vancomycin at a concentration of 1000 μg / mL. A model control group was also included, with a volume of 3 mL per well. After treatment at 28℃ for 24 h, Staphylococcus aureus was administered to each experimental group in water. After another 6 h of treatment at 28℃, 10 zebrafish from each experimental group were randomly selected and photographed under a fluorescence microscope. Data were analyzed and collected using NIS-Elements D 3.20 advanced image processing software. The fluorescence intensity of Staphylococcus aureus in the zebrafish intestine was analyzed, and the antibacterial efficacy of the samples was evaluated using statistical analysis of this index. Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software; p < 0.05 indicated statistical significance.

[0106] Then, the fluorescence intensity of Staphylococcus aureus in the gut was reduced compared to the model control group in both the examples and the comparative examples, and for each example, the sum of the fluorescence intensity (pixel) values ​​of Staphylococcus aureus in the gut reduced compared to the model control group and the unit dose contribution value were calculated in the manner described above.

[0107] Following the above method, zebrafish were administered MLCT and partially hydrolyzed protein at different ratios to evaluate their inhibitory efficacy against Staphylococcus aureus. The dosages are shown in Table 2. The results are also shown in Table 2. Figure 3 and Figure 4 As shown.

[0108] Table 2. Experimental results evaluating the efficacy of samples in inhibiting Staphylococcus aureus (n = 10)

[0109]

[0110] Note: Compared with the model control group, This indicates that p < 0.05. This indicates that p < 0.01. This indicates that p < 0.001;

[0111] Compared with Comparative Example 1, !! indicates p < 0.01, and !!! indicates p < 0.001;

[0112] Compared with Comparative Example 2, @ indicates p < 0.05, and @@@ indicates p < 0.001;

[0113] Compared with Comparative Example 3, ## indicates p < 0.01, and ### indicates p < 0.001;

[0114] Compared with Comparative Example 4, $$ indicates p < 0.01;

[0115] Compared with Comparative Example 5, %% indicates p < 0.01, and %%% indicates p < 0.001.

[0116] From Table 2, Figure 3 and Figure 4 The results showed that, compared with the model control group, the positive control (vancomycin, 1000 µg / mL), single-component MLCT (125 μg / mL), and single-component partially hydrolyzed protein (3.12 μg / mL, 12.5 μg / mL, and 50 μg / mL) and Examples 1-7 all had significant inhibitory effects on Staphylococcus aureus, specifically manifested as a significant decrease in the fluorescence intensity of Staphylococcus aureus in the zebrafish intestine (P<0.05).

[0117] Example 1 (MLCT to partially hydrolyzed protein weight ratio of 1.6) is equivalent to a combination of Comparative Example 1 (MLCT 5 µg / mL) and Comparative Example 4 (single-component partially hydrolyzed protein 3.12 µg / mL). Compared with the model control group, Example 1 showed a reduction of 148,981 in the fluorescence intensity (pixels) of Staphylococcus aureus in the intestine, while Comparative Examples 1 and 4 showed reductions of 23,137 and 83,945, respectively. The former was greater than the sum of the latter two (107,082), indicating that Example 1 had a synergistic effect in inhibiting Staphylococcus aureus. Similarly, Examples 2-7 also showed a synergistic effect in inhibiting Staphylococcus aureus.

[0118] Furthermore, Examples 1-5 and 7 (MLCT to partially hydrolyzed protein weight ratio of 0.1-10) showed a greater contribution per unit dose compared to Example 6 (MLCT to partially hydrolyzed protein weight ratio of 40), indicating that the synergistic effect of MLCT and partially hydrolyzed protein in inhibiting Staphylococcus aureus was more significant at this weight ratio.

[0119] Furthermore, Examples 1-5 (MLCT to partially hydrolyzed protein weight ratio of 0.1-8) showed a greater contribution per unit dose compared to Examples 6 and 7 (MLCT to partially hydrolyzed protein weight ratios of 40 and 10, respectively), indicating that the synergistic effect of MLCT and partially hydrolyzed protein in inhibiting Staphylococcus aureus was more significant at this weight ratio.

[0120] Furthermore, Examples 1, 2, 4, and 5 (MLCT to partially hydrolyzed protein weight ratio of 0.4-8) showed a greater contribution per unit dose compared to Examples 3, 6, and 7 (MLCT to partially hydrolyzed protein weight ratios of 0.1, 40, and 10, respectively), indicating that the synergistic effect of MLCT and partially hydrolyzed protein in inhibiting Staphylococcus aureus was more significant at this weight ratio.

[0121] Furthermore, Examples 1, 2, and 5 (MLCT to partially hydrolyzed protein weight ratio of 0.4-2) showed a greater contribution per unit dose compared to Examples 3, 4, 6, and 7 (MLCT to partially hydrolyzed protein weight ratios of 0.1, 8, 40, and 10, respectively), indicating that the synergistic effect of MLCT and partially hydrolyzed protein in inhibiting Staphylococcus aureus was more significant at this weight ratio.

[0122] Furthermore, Examples 1 and 2 (MLCT to partially hydrolyzed protein weight ratio of 0.4-1.6) showed a greater contribution per unit dose compared to Examples 3-7 (MLCT to partially hydrolyzed protein weight ratios of 0.1, 8, 2, 40 and 10, respectively), indicating that the synergistic effect of MLCT and partially hydrolyzed protein in inhibiting Staphylococcus aureus was more significant at this weight ratio.

[0123] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A nutritional composition comprising partially hydrolyzed protein and medium- and long-chain fatty acid triglycerides.

2. The nutritional composition according to claim 1, wherein the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein is 0.1-40.

3. The nutritional composition according to claim 1, wherein the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein is 0.1-10.

4. The nutritional composition according to claim 1, wherein the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein is 0.1-8.

5. The nutritional composition according to claim 1, wherein the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein is 0.4-8.

6. The nutritional composition according to claim 1, wherein the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein is 0.4-2.

7. The nutritional composition according to claim 1, wherein the weight ratio of the medium- and long-chain fatty acid triglycerides to the partially hydrolyzed protein is 0.4-1.

6.

8. The nutritional composition according to claim 1, wherein the partially hydrolyzed protein is selected from partially hydrolyzed whey protein or partially hydrolyzed milk protein.

9. The nutritional composition according to claim 1, wherein the degree of hydrolysis of the partially hydrolyzed protein is 7%-25%.

10. The nutritional composition according to claim 1, wherein the degree of hydrolysis of the partially hydrolyzed protein is 7%-17%.

11. The nutritional composition according to claim 1, wherein the degree of hydrolysis of the partially hydrolyzed protein is 7%-15%.

12. A product comprising the nutritional composition according to any one of claims 1-11.

13. The product according to claim 12, wherein the product is food or medicine.

14. The product of claim 13, wherein the food is selected from dairy products, confectionery, beverages, fermented foods, bread, and biscuits.

15. The product according to claim 14, wherein the dairy product is selected from milk powder, modified milk powder, formula powder or solid beverage.

16. The product according to any one of claims 12-15, characterized by The product contains 0.1%-50% partially hydrolyzed protein and 0.1%-30% medium- and long-chain fatty acid triglycerides, based on the total dry weight of the product.

17. Use of the nutritional composition according to any one of claims 1-11 in the preparation of products for improving gut health.

18. The use according to claim 17, wherein improving gut health includes improving diarrhea.

19. The use according to claim 18, wherein the diarrhea is caused by Staphylococcus aureus.

20. The use according to claim 17, wherein improving gut health includes inhibiting Staphylococcus aureus.

21. The use according to claim 20, wherein inhibiting Staphylococcus aureus includes inhibiting the growth, proliferation, or production of metabolites of Staphylococcus aureus.

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