WO2023098541A1 - 可提升生物体对金黄色葡萄球菌感染抵御能力的益生元与益生菌组合物 - Google Patents

可提升生物体对金黄色葡萄球菌感染抵御能力的益生元与益生菌组合物 Download PDF

Info

Publication number
WO2023098541A1
WO2023098541A1 PCT/CN2022/133820 CN2022133820W WO2023098541A1 WO 2023098541 A1 WO2023098541 A1 WO 2023098541A1 CN 2022133820 W CN2022133820 W CN 2022133820W WO 2023098541 A1 WO2023098541 A1 WO 2023098541A1
Authority
WO
WIPO (PCT)
Prior art keywords
day
cfu
food
bifidobacterium longum
oligosaccharides
Prior art date
Application number
PCT/CN2022/133820
Other languages
English (en)
French (fr)
Inventor
怀斯吉塞拉·阿德里安娜
凡·鲁-鲍曼卡洛琳·安妮卡
施密特盖瑞特
闫雅璐
王雯丹
司徒文佑
刘彪
刘伟贤
洪维鍊
Original Assignee
内蒙古伊利实业集团股份有限公司
内蒙古乳业技术研究院有限责任公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 内蒙古伊利实业集团股份有限公司, 内蒙古乳业技术研究院有限责任公司 filed Critical 内蒙古伊利实业集团股份有限公司
Publication of WO2023098541A1 publication Critical patent/WO2023098541A1/zh

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/16—Agglomerating or granulating milk powder; Making instant milk powder; Products obtained thereby
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/20—Dietetic milk products not covered by groups A23C9/12 - A23C9/18
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/20—Dietetic milk products not covered by groups A23C9/12 - A23C9/18
    • A23C9/203—Dietetic milk products not covered by groups A23C9/12 - A23C9/18 containing bifidus-active substances, e.g. lactulose; containing oligosaccharides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention mainly relates to a prebiotic and probiotic composition capable of improving the organism's resistance to Staphylococcus aureus infection and its application, specifically to a composition containing Bifidobacterium longum subsp. infantis ) and human milk oligosaccharides (Human Milk Oligosaccharides, referred to as HMOs) in the preparation of food or medicine for improving the resistance of organisms to Staphylococcus aureus infection.
  • HMOs Human Milk Oligosaccharides
  • breastfed infants Over the last millennium, it has been documented in the medical literature that infants who are not breastfed have higher rates of disease and mortality.
  • Breast milk not only provides the necessary nutrition for the baby, but also the active ingredients in breast milk provide protection for the baby's intestinal development and immunity.
  • Breastfed infants have a higher relative abundance of beneficial bacteria in the gut microbiota, especially bifidobacteria and lactic acid bacteria, compared with formula-fed infants.
  • HMOs Human Milk Oligosaccharides
  • Breast milk oligosaccharides are mainly composed of three categories: (1) fucosyl oligosaccharides, with 2'-fucosyl oligosaccharides and 3'-fucosyl oligosaccharides as representative substances; (2) Sialyl oligosaccharides, represented by 3'-sialyl lactose and 6'-sialyl lactose; (3) Core sugar chain structure without fucosyl or sialic acid groups The formed oligosaccharides are represented by lactose-N-tetraose and lactose-N-neotetraose.
  • HMOs have become a gap that must be crossed for infant formula powder to be closer to the composition of breast milk.
  • the first clinical intervention trial using 2'-FL demonstrated that the inclusion of this specific ingredient in a low-calorie formula is not only safe but also allows formula-fed infants to grow at rates comparable to breastfed infants.
  • 2’-FL is also used as a nutritional supplement for adults to relieve irritable bowel syndrome or inflammatory bowel disease, or as a prebiotic to maintain the balance of intestinal flora.
  • Gut flora is an important component of the human intestinal micro-ecosystem and plays an important role in human health, such as providing essential nutrients, producing vitamin K, assisting the digestive process, and promoting angiogenesis and intestinal nerve function. Both prebiotics and probiotics are regarded as microecological management tools to improve the body's health, which can change, regulate and reorganize the existing intestinal flora.
  • Caenorhabditis elegans As a model organism, Caenorhabditis elegans (C.elegans) has good application prospects in preclinical research and evaluation. It has a short life cycle (21 days), is highly replicable and reproducible, and is easy to operate, transparent and easy to cultivate. Its genome has been fully sequenced, and a quarter of its genes are homologous to the human genome.
  • the genetically mutated nematode organisms produced by editing the genes of nematodes can be used as experimental means for genetic analysis. Nematodes are not currently considered an animal in European legislation. It is widely used as an in vitro assay, such as transcriptomics, proteomics, metabolomics, etc.
  • As a model organism it is often used as the first step in the evaluation of raw materials. Before the design of functional raw materials, in vitro enzyme or cell experiments, mouse models and clinical experiments, nematodes are often used as a high-throughput method to screen test raw materials some of the characteristics.
  • Staphylococcus aureus (S.aureus) is a Gram-positive bacterium belonging to the genus Staphylococcus and a common food-borne pathogenic microorganism. It exists widely in the natural environment. Under appropriate conditions, it can produce enterotoxin and cause food poisoning, causing many food-borne microbial food poisoning incidents caused by Staphylococcus aureus. After the human body is infected by Staphylococcus aureus, common food poisoning symptoms such as nausea, vomiting, and dizziness may occur, and symptoms such as enteritis, pneumonia, skin infection, wound infection and ulceration, and meningitis may occur.
  • the inventors of this case found in their research that the combination of Bifidobacterium longum subsp. infantis and breast milk oligosaccharides can improve the organism's resistance to Staphylococcus aureus infection, improve the organism's innate immunity and/or Anti-aging works synergistically.
  • the present invention provides an application of a composition of prebiotics and probiotics in the preparation of food or medicine, wherein the prebiotics include breast milk oligosaccharides, and the probiotics include Bifidobacterium longum Subspecies (Bifidobacterium longum subsp. infantis), the food or drug is a food or drug used for at least one of the following functions:
  • Anti-aging especially anti-immunosenescence (immunosenescence).
  • the present invention also provides the use of breast milk oligosaccharides in improving the resistance of the organism to Staphylococcus aureus infection, improving the innate immunity of the organism and/or anti-aging aspects of use.
  • the Bifidobacterium longum subsp. infantis includes the bacterial strain whose preservation number is CGMCC No.21109.
  • the Bifidobacterium longum subsp. infantis strain with the preservation number CGMCC No. 21109 was deposited in the General Microbiology Center (CGMCC) of the China Committee for the Collection of Microbial Cultures on December 05, 2020.
  • CGMCC General Microbiology Center
  • This strain is also referred to as YLGB-1496 or GB-1496 in the present invention.
  • the human milk oligosaccharides include 2'-fucosyllactose, 3'-fucosyllactose, lactose-N-tetraose, 3'- One or more of sialyllactose and 6'-sialyllactose.
  • 2'-fucosyllactose (2'-FL), a trisaccharide structure formed by fucose and lactose, is a representative substance of fucosyl oligosaccharides.
  • the commercially available substance is usually prepared by microbial fermentation and has the same structure as 2'-fucosyllactose found in human milk.
  • 3-fucosyllactose (3-FL), a trisaccharide structure formed by fucose and lactose, is isomers with 2'-fucosyllactose. It is a representative substance of fucosyl oligosaccharides. The commercially available substance is usually produced by microbial fermentation and has the same structure as 3-fucosyllactose found in human milk.
  • Lactose-N-tetraose (lacto-N-tetraose, LNT), a hexasaccharide structure formed by lactose and tetrasaccharide, is based on the core sugar chain and does not contain fucosyl or sialic acid groups.
  • a representative substance of sugar The commercially available substance is usually produced by microbial fermentation and has the same structure as lactose-N-tetraose found in human milk.
  • 3'-sialyllactose (3'-sialyllactose, 3'-SL), is a trisaccharide structure formed by sialic acid and lactose, and is isomers with 6'-sialyllactose. Representative substances of oligosaccharides.
  • the commercially available substance is usually produced by microbial fermentation and has the same structure as 3'-sialyllactose found in human milk.
  • 6'-sialyllactose (6'-sialyllactose, 6'-SL), is a trisaccharide structure formed by sialic acid and lactose, and is isomers with 3'-sialyllactose, which is a sialic acid group Representative substances of oligosaccharides.
  • the commercially available substance is usually produced by microbial fermentation and has the same structure as 6'-sialyllactose found in human milk.
  • the human milk oligosaccharides include at least one of fucosyl oligosaccharides, sialyl oligosaccharides, and N-acetylated oligosaccharides .
  • the breast milk oligosaccharides are fucosyl oligosaccharides; preferably 2'-fucosyllactose, 3'-fucosyllactose .
  • the breast milk oligosaccharides are N-acetylated oligosaccharides; preferably lactose-N-tetraose, lactose-N-neotetraose.
  • the breast milk oligosaccharide is a sialyl oligosaccharide, preferably one of 3'-sialyl lactose and 6'-sialyl lactose one or more species.
  • the human milk oligosaccharides include 2'-fucosyllactose.
  • the content of 2'-fucosyllactose in the human milk oligosaccharides may be more than 80%, such as more than 85%, more than 90%, more than 95%, or 100%.
  • the content of 2'-fucosyllactose in the human milk oligosaccharides is 0%-73%, preferably 0%-63%, further Preferably 0%-58%, more preferably 2%-55%, such as 3%-8%, 25%-35% or 51%-56%, more specifically 5%, 30% or 53% %.
  • the ratio of the Bifidobacterium longum subsp. infantis to the breast milk oligosaccharide is 1 ⁇ 10 8 CFU:0.08g ⁇ 0.3g.
  • the ratio of the bifidobacterium longum infant subspecies to the breast milk oligosaccharide is based on the amount of the two in the same composition.
  • the organism in the application of the composition of the present invention, includes animals or humans.
  • the animal is preferably a mammal.
  • the composition of the present invention is used in the preparation of food or medicine that can effectively improve the organism's resistance to Staphylococcus aureus infection, improve the organism's innate immunity and/or anti-aging effect
  • said improving the ability of organisms to resist Staphylococcus aureus infection includes: improving the ability of individuals to prevent Staphylococcus aureus infection, reducing the ability of individuals infected by Staphylococcus aureus, and/or alleviating various symptoms caused by Staphylococcus aureus infection Symptoms such as food poisoning (including nausea, vomiting, dizziness, etc.), enteritis, pneumonia, skin infection, wound ulceration, or meningitis.
  • the composition of the present invention can be used to prepare various health foods, health care products, medicines and the like.
  • the food may be liquid beverage, solid beverage, oral liquid, milk product, tablet or capsule and the like.
  • the food is food for infants and young children (including formula powder for infants and young children, food supplements, nutritional supplements), or nutritional supplements or food for children over 3 years old, adolescents or adults (such as non-infant food Infant milk powder) has broad application prospects.
  • the medicine can be an oral preparation, or an external preparation, such as ointment for application.
  • the present invention also provides a food, which contains Bifidobacterium longum infant subspecies and breast milk oligosaccharides, wherein:
  • the breast milk oligosaccharides include one of 2'-fucosyllactose, 3'-fucosyllactose, lactose-N-tetraose, 3'-sialyl lactose and 6'-sialyllactose one or more kinds;
  • the human milk oligosaccharides include 2'-fucosyllactose
  • said Bifidobacterium longum subsp. infantis includes the bacterial strain whose preservation number is CGMCC No.21109.
  • the application amount of the Bifidobacterium longum subspecies in food is 1 ⁇ 10 3 CFU/day to 1 ⁇ 10 12 CFU/day, more preferably 1 ⁇ 10 6 CFU/day ⁇ 1 ⁇ 10 11 CFU/day;
  • the amount of human milk oligosaccharides used in food is 0.015g/day to 15g/day, more preferably 0.1g/day to 12g/day, more preferably 1.5g/day to 10g/day;
  • the food is food for at least one of the following effects: improving the resistance of the organism to Staphylococcus aureus infection; improving the innate immunity of the organism; and/or anti-aging, especially anti-immunoaging.
  • the application amount of Bifidobacterium lactis in the food is 1 ⁇ 10 8 CFU/day.
  • the application amount of the human milk oligosaccharides in the food is 0.015g/day to 15g/day, more preferably 0.1g/day to 12g/day, more preferably 1.5g/day day ⁇ 10g/day.
  • the present invention also provides a method for improving the resistance of organisms to Staphylococcus aureus infection, improving the innate immunity and/or anti-aging of organisms, the method comprising administering an effective amount of probiotics to organisms in need A composition of probiotics and probiotics, wherein the prebiotics include breast milk oligosaccharides, and the probiotics include Bifidobacterium longum subsp. infantis.
  • the anti-aging is anti-immunoaging.
  • the Bifidobacterium longum infantis subspecies includes a bacterial strain whose preservation number is CGMCC No.21109.
  • the amount of Bifidobacterium longum subsp. infantis administered to organisms in need is 1 ⁇ 10 3 CFU/day to 1 ⁇ 10 12 CFU/day, preferably 1 ⁇ 10 6 CFU/day day to 1 ⁇ 10 11 CFU/day.
  • the amount of human milk oligosaccharides administered to organisms in need is 0.015 g/day to 15 g/day, more preferably 0.1 g/day to 12 g/day, more preferably 1.5 g/day day ⁇ 10g/day.
  • the food or medicine comprising the prebiotic and probiotic composition of the present invention has the ability to improve the resistance of organisms to Staphylococcus aureus infection, and has the ability to improve the innate ability of organisms Immunity and/or anti-aging benefits.
  • Figure 1 shows the effect of 15 mg/mL of human milk oligosaccharide 2'-FL and probiotic YLGB-1496 composition on the survival rate of Caenorhabditis elegans infected by Staphylococcus aureus.
  • Bifidobacterium infantis YLGB-1496 (or GB-1496) strain Bifidobacterium infantis YLGB-1496 (or GB-1496) strain:
  • CGMCC General Microbiology Center
  • the probiotics Bifidobacterium longum infant subspecies YLGB-1496 or GB-1496 used in the present invention (the source is the breast milk of Chinese healthy mothers, has been preserved in the General Microbiology Center (CGMCC) of China Microbiological Culture Collection Management Committee on December 05, 2020 ), depositor address: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing, Institute of Microbiology, Chinese Academy of Sciences, deposit date: December 05, 2020; deposit number: CGMCC No.21109; classification name: Bifidobacterium longum Infant subspecies (Bifidobacterium longum subsp. infantis)).
  • CGMCC General Microbiology Center
  • the tested probiotics were grown in MRS medium supplemented with 1% cysteine and incubated overnight at 37°C in an anaerobic environment.
  • the cells were harvested and rinsed with physiological saline solution, and the concentration of probiotics was adjusted to inoculate them on plates containing nematode growth medium.
  • the probiotics in each plate were 1 ⁇ 10 8 CFU or 1 ⁇ 10 7 CFU.
  • the HMO raw materials used in the present invention all come from Jennewein. Prepare the human milk oligosaccharide solution with distilled water.
  • Nematodes of the same age were obtained and cultured in a petri dish containing nematode agar medium (NGM medium, nematode medium containing Escherichia coli OP50 as food), and different doses of HMO (15mg/mL) and probiotics were added Bacteria (1 ⁇ 10 8 CFU, 1 ⁇ 10 7 CFU) composition for co-cultivation (the total volume of liquid added to each nematode culture dish is 10 mL. For the HMO test group with a concentration of 15 mg/mL, each culture dish The final amount of HMO in the medium is 150mg.
  • the ratio of probiotics to HMO is: 1 ⁇ 10 8 CFU: 150mg, or 1 ⁇ 10 7 CFU: 150mg).
  • Example 1 The composition of human milk oligosaccharides and probiotics YLGB-1496 has a golden yellow effect on Caenorhabditis elegans Influence of Survival Rate During Staphylococcal Infection
  • Embodiment 2 Combination of added breast milk oligosaccharides and Bifidobacterium longum infant subspecies YLGB-1496 composition formula powder
  • This embodiment provides an infant formula milk powder, the total protein content in the formula milk powder is 11.1g/100g powder, the fat content is 28.3g/100g powder, the carbohydrate content is 52.9g/100g powder, breast milk oligosaccharide 2'- FL content is 1.5g/100g powder, and Bifidobacterium longum subsp. infantis YLGB-1496 is 1 ⁇ 10 8 CFU/100g powder.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Mycology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nutrition Science (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

提供了一种益生元与益生菌的组合物在制备食品或药品中的应用，其中，所述益生元包括母乳低聚糖，所述益生菌包括长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)，所述食品或药品是用于以下至少一种功效的食品或药品：提升生物体对金黄色葡萄球菌感染的抵御能力；提高生物体先天免疫；和/或抗衰老。所述长双歧杆菌婴儿亚种优选包括保藏编号为CGMCC No.21109的菌株。

Description

可提升生物体对金黄色葡萄球菌感染抵御能力的益生元与益生菌组合物 技术领域
本发明主要是关于一种可提升生物体对金黄色葡萄球菌感染抵御能力的益生元与益生菌组合物及其应用，具体是指一种包含长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)与母乳低聚糖(Human Milk Oligosaccharides，简称HMOs)的组合物在制备用于提升生物体对金黄色葡萄球菌感染的抵御能力的食品或药品中的应用。
背景技术
在上个千年，已有医学文献记载，未经母乳喂养的婴儿有较高的疾病率和死亡率。母乳不仅为婴儿提供所需营养，母乳中的活性成分更为婴儿的肠道发育和免疫力完善提供保障。母乳喂养的婴儿与配方奶喂养的婴儿相比，肠道菌群中有益菌的相对丰度更高，特别是双歧杆菌和乳酸菌。
母乳通过菌群的传递，加上母乳低聚糖和母乳中的细胞因子等活性成分，为新生儿建立起健康的肠道菌群。婴儿每天通过母乳摄入10 7～10 8个细菌，包括乳酸菌和双歧杆菌。这些菌通过母乳直接传递给婴儿，部分可在婴儿肠道定植，促进生命早期肠道菌群的建立。婴儿肠道菌群的建立，对其肠道的发育，以及对健康和免疫系统有着短期，甚至终生的影响。
母乳低聚糖(Human Milk Oligosaccharides，简称HMOs)属于母乳中除乳糖和脂肪外，含量第三丰富的物质。其总含量在泌乳期的各个阶段有变化，在成熟乳中大约是12～14g/L，而初乳中大约是20～24g/L。每一种母乳低聚糖的结构在还原端都有一个乳糖，大部分以聚乳糖胺作为结构主链，并在链端含有岩藻糖、唾液酸或二者均有。母乳低聚糖主要由三大类组成：(1)岩藻糖基类低聚糖，以2’-岩藻糖基低聚糖和3’-岩藻糖基低聚糖为代表性物质；(2)唾液酸基类低聚糖，以3’-唾液酸基乳糖和6’-唾液酸基乳糖为代表性物质；(3)不含岩藻糖基或唾液酸基的核心糖链结构形成的低聚糖，以乳糖-N-四糖和乳糖-N-新四糖为代表性物质。
HMOs的存在与含量存在个体差异，并与哺乳母亲的路易斯分泌型组成有关。由于婴幼儿配方粉的原料通常是牛乳，而牛乳中通常不含或含有很少这类低聚糖物质， HMOs便成为了婴幼儿配方粉想要更加接近母乳成分所必须跨越的一道鸿沟。
上世纪90年代，作为在大部分母乳中均含有的HMO，2-岩藻糖基乳糖(2’-FL)被发现可有效地减轻大肠杆菌中稳定毒素的毒性；到了2003年，该低聚糖被报道可抑制弯曲空肠杆菌的附着和感染。随后，母乳低聚糖的三大主要功能被逐步报道和发现：(1)抑制特定病菌的附着和感染；(2)作为益生元，促进肠道共生系统里面细菌的生长；(3)直接减缓粘膜在有毒刺激下的炎症反应。使用了2’-FL的首个临床干预试验证实了在低卡路里配方中加入这个特定成分不仅安全还可以让配方奶喂养的婴儿生长速率与母乳喂养的婴儿具有可比性。2’-FL也被用作成年人的营养补充剂，缓解肠道应激性综合症或炎症性肠病，或被用作益生元维持肠道菌群平衡。
肠道菌群是人体肠道微生态系统的重要组成物质，对人类健康有重要作用，如可提供必需营养素，生成维生素K，辅助消化过程与促进血管生成和肠道神经作用。益生元和益生菌均被视为改善机体健康的微生态管理工具，可改变、调节和重组已经存在的肠道菌群。
目前在婴幼儿配方粉、辅食及营养补充剂领域，需要有缓解婴幼儿肠道不适及提升自身抵御致病菌如金黄色葡萄球菌感染能力的解决方案。同时，在3岁以上儿童、青少年及成人领域，也需要缓解肠道不适及提升自身抵御致病菌如金黄色葡萄球菌感染能力的解决方案。
秀丽隐杆线虫(C.elegans)作为一种模型生物，在临床前研究与评估中有较好的应用前景。它具有较短的生命周期(21天)，可复制和再生性较强，操作简便、透明且易于培养。它的基因组已全部被测序，并且有四分之一的基因与人类基因组是同源的。对线虫的基因进行编辑从而产生的基因突变的线虫生物体，可用作基因分析的实验手段。目前线虫在欧洲的立法中并不被认为是一种动物。它被广泛用作活体外的测定，比如转录组学、蛋白组学、代谢组学等。作为模式生物，它也常常被作为原料评估的第一个步骤，在功效原料的设计、体外酶或细胞实验、小鼠模型和临床实验前，往往用线虫作为高通量的手段来筛选测试原料的一些特性。
金黄色葡萄球菌(Staphylococcus aureus,S.aureus)是一种革兰氏阳性菌，属于葡萄球菌属，是常见的食源性致病微生物。它广泛存在于自然环境中，在适当条件下，能产生肠毒素并能引起食物中毒，引发过多起由金黄色葡萄球菌导致的食源性微生物食物中毒事件。人体在受到金黄色葡萄球菌感染后，可能会出现恶心、呕吐、头晕等 常见的食物中毒症状，并可能出现肠炎、肺炎、皮肤感染、伤口感染溃烂、脑膜炎等症状。
发明内容
本案发明人在研究中发现，长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)和母乳低聚糖组合，对于提高生物体对金黄色葡萄球菌感染抵御能力、提高生物体先天免疫和/或抗衰老具有协同作用。
从而，一方面，本发明提供了一种益生元与益生菌的组合物在制备食品或药品中的应用，其中，所述益生元包括母乳低聚糖，所述益生菌包括长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)，所述食品或药品是用于以下至少一种功效的食品或药品：
提升生物体对金黄色葡萄球菌感染的抵御能力；
提高生物体先天免疫；和/或
抗衰老特别是抗免疫衰老(immunosenescence)。
另一方面，本发明还提供了母乳低聚糖在用于提升所述长双歧杆菌婴儿亚种在提升生物体对金黄色葡萄球菌感染的抵御能力、提高生物体先天免疫和/或抗衰老方面的用途。
根据本发明的具体实施方案，本发明中，所述长双歧杆菌婴儿亚种包括保藏编号为CGMCC No.21109的菌株。
保藏编号为CGMCC No.21109的长双歧杆菌婴儿亚种菌株已于2020年12月05日保藏于中国微生物菌种保藏管理委员会普通微生物中心(CGMCC)，保藏单位地址：北京市朝阳区北辰西路1号院3号，中国科学院微生物研究所，保藏日期：2020年12月05日；保藏编号：CGMCC No.21109；分类命名：长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)。本发明中将该菌株也称为YLGB-1496或GB-1496。
根据本发明的具体实施方案，本发明的组合物中，所述母乳低聚糖包括2’-岩藻糖基乳糖、3’-岩藻糖基乳糖、乳糖-N-四糖、3’-唾液酸基乳糖、6’-唾液酸基乳糖中的一种或多种。
2’-岩藻糖基乳糖(2’-fucosyllactose，2’-FL)，为岩藻糖与乳糖形成的三糖结构，是 岩藻糖基类低聚糖的代表性物质。市售该物质通常为经微生物发酵法制备，与人乳中发现的2’-岩藻糖基乳糖具有相同结构。
3-岩藻糖基乳糖(3-fucosyllactose，3-FL)，为岩藻糖与乳糖形成的三糖结构，与2’-岩藻糖基乳糖互为同分异构体。是岩藻糖基类低聚糖的代表性物质。市售该物质通常为经微生物发酵法制备，与人乳中发现的3-岩藻糖基乳糖具有相同结构。
乳糖-N-四糖(lacto-N-tetraose，LNT)，为乳糖与四糖形成的六糖结构，是以核心糖链为基础结构，且不含岩藻糖基或唾液酸基的低聚糖的代表性物质。市售该物质通常为经微生物发酵法制备，且与人乳中发现的乳糖-N-四糖具有相同结构。
3’-唾液酸基乳糖(3’-sialyllactose，3’-SL)，为唾液酸与乳糖形成的三糖结构，与6’-唾液酸基乳糖互为同分异构体，是唾液酸基类低聚糖的代表性物质。市售该物质通常为经微生物发酵法制备，与人乳中发现的3’-唾液酸基乳糖具有相同结构。
6’-唾液酸基乳糖(6’-sialyllactose，6’-SL)，为唾液酸与乳糖形成的三糖结构，与3’-唾液酸基乳糖互为同分异构体，是唾液酸基类低聚糖的代表性物质。市售该物质通常为经微生物发酵法制备，与人乳中发现的6’-唾液酸基乳糖具有相同结构。
根据本发明的一些具体实施方案，本发明的组合物中，所述母乳低聚糖包括岩藻糖基低聚糖、唾液酸基低聚糖、N-乙酰化低聚糖中的至少一种。
根据本发明的一些具体实施方案，本发明的组合物中，所述母乳低聚糖为岩藻糖基低聚糖；优选为2’-岩藻糖基乳糖、3’-岩藻糖基乳糖。
根据本发明的一些具体实施方案，本发明的组合物中，所述母乳低聚糖为N-乙酰化低聚糖；优选为乳糖-N-四糖、乳糖-N-新四糖。
根据本发明的一些具体实施方案，本发明的组合物中，所述母乳低聚糖为唾液酸基低聚糖，优选为3’-唾液酸基乳糖、6’-唾液酸基乳糖中的一种或多种。
根据本发明的一些具体实施方案，本发明的组合物中，所述母乳低聚糖包括2’-岩藻糖基乳糖。2’-岩藻糖基乳糖在所述母乳低聚糖中的含量可为80％以上，例如85％以上，90％以上，95％以上，或100％。
根据本发明的一些具体实施方案，本发明的组合物中，2’-岩藻糖基乳糖在所述母乳低聚糖中的含量为0％-73％，优选为0％-63％，进一步优选为0％-58％，更进一步优选为2％-55％，例如可以为3％-8％、25％-35％或51％-56％，更具体可以为5％、30％或53％。
根据本发明的具体实施方案，本发明的组合物中，所述长双歧杆菌婴儿亚种与母乳低聚糖的比例为1×10 3CFU～1×10 12CFU：0.1g～10g，优选为1×10 6CFU～1×10 10CFU：1g～10g。在本发明的一些更具体实施方案中，所述长双歧杆菌婴儿亚种与母乳低聚糖的比例为1×10 8CFU：0.08g～0.3g。所述长双歧杆菌婴儿亚种与母乳低聚糖的比例是以二者在同一组合物中的用量计。
根据本发明的具体实施方案，本发明的组合物的应用中，所述生物体包括动物或人。所述动物优选为哺乳动物。
根据本发明的具体实施方案，本发明的组合物在制备具有可有效提升生物体对金黄色葡萄球菌感染的抵御能力、可提高生物体先天免疫和/或抗衰老功效的食品或药品中的应用中，所述提升生物体对金黄色葡萄球菌感染抵御能力包括：提升个体预防金黄色葡萄球菌感染的能力，降低金黄色葡萄球菌感染个体的能力，和/或缓解金黄色葡萄球菌感染引起的各种症状例如食物中毒(包括恶心、呕吐、头晕等)、肠炎、肺炎、皮肤感染、伤口溃烂或脑膜炎等。
根据本发明的具体实施方案，本发明的组合物可用于制备各种健康食品、保健品以及药品等。具体地，所述食品可以为液体饮料、固体饮料、口服液、奶制品、片剂或胶囊等。在本发明的一些具体实施方案中，所述食品为婴幼儿食品(包括婴幼儿配方粉、辅食、营养补充剂)，或3岁以上儿童、青少年或成人的营养补充剂或食品(例如非婴幼儿乳粉)中，具有广阔的应用前景。所述药品可以是口服制剂，也可以是外用制剂，例如涂抹用药膏等。
本发明还提供了一种食品，其中包含有长双歧杆菌婴儿亚种与母乳低聚糖，其中：
所述母乳低聚糖包括2’-岩藻糖基乳糖、3’-岩藻糖基乳糖、乳糖-N-四糖、3’-唾液酸基乳糖、6’-唾液酸基乳糖中的一种或多种；
优选地，所述母乳低聚糖包括2’-岩藻糖基乳糖；
优选地，所述长双歧杆菌婴儿亚种包括保藏编号为CGMCC No.21109的菌株。
根据本发明的具体实施方案，本发明的食品中，所述长双歧杆菌婴儿亚种在食品中的应用量为1×10 3CFU/天～1×10 12CFU/天，更优选为1×10 6CFU/天～1×10 11CFU/天；
优选地，所述母乳低聚糖在食品中的应用量为0.015g/天～15g/天，进一步优选为0.1g/天～12g/天，更优选为1.5g/天～10g/天；
所述食品是用于以下至少一种功效的食品：提升生物体对金黄色葡萄球菌感染的 抵御能力；提高生物体先天免疫；和/或抗衰老特别是抗免疫衰老。
在本发明的一些具体实施例方案中，乳双歧杆菌在所述食品中的应用量为1×10 8CFU/天。
根据本发明的具体实施方案，所述母乳低聚糖在所述食品中的应用量为0.015g/天～15g/天，进一步优选为0.1g/天～12g/天，更优选为1.5g/天～10g/天。
另一方面，本发明还提供了一种提升生物体对金黄色葡萄球菌感染的抵御能力、提高生物体先天免疫和/或抗衰老的方法，该方法包括给予有需要的生物体有效量的益生元与益生菌的组合物，其中，所述益生元包括母乳低聚糖，所述益生菌包括长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)。
根据本发明的具体实施方案，所述抗衰老为抗免疫衰老。
根据本发明的具体实施方案，所述长双歧杆菌婴儿亚种包括保藏编号为CGMCC No.21109的菌株。
根据本发明的具体实施方案，所述长双歧杆菌婴儿亚种给予有需要的生物体的量为1×10 3CFU/天～1×10 12CFU/天，优选为1×10 6CFU/天～1×10 11CFU/天。
根据本发明的具体实施方案，所述母乳低聚糖给予有需要的生物体的量为0.015g/天～15g/天，进一步优选为0.1g/天～12g/天，更优选为1.5g/天～10g/天。
本发明的包括所述益生元和益生菌组合物的食品或药品，因包括所述益生元和益生菌组合物而具有可提升生物体对金黄色葡萄球菌感染抵御能力，具有可提高生物体先天免疫和/或抗衰老功效。
附图说明
图1显示15mg/mL的母乳低聚糖2’-FL与益生菌YLGB-1496组合物对秀丽隐杆线虫受到金黄色葡萄球菌感染时存活率的影响。
用于专利程序的微生物保藏：
婴儿双歧杆菌YLGB-1496(或GB-1496)菌株：
保藏日期：2020年12月05日；
保藏单位：中国微生物菌种保藏管理委员会普通微生物中心(CGMCC)；
保藏单位地址：北京市朝阳区北辰西路1号院3号，中国科学院微生物研究所；
保藏编号：CGMCC No.21109；
分类命名：长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)。
具体实施方式
为了对本发明的技术特征、目的和有益效果有更加清楚的理解，现对本发明的技术方案进行以下详细说明，但不能理解为对本发明的可实施范围的限定。
本发明中所用益生菌长双歧杆菌婴儿亚种YLGB-1496或GB-1496(来源为中国健康妈妈母乳，已于2020年12月05日保藏于中国微生物菌种保藏管理委员会普通微生物中心(CGMCC)，保藏单位地址：北京市朝阳区北辰西路1号院3号，中国科学院微生物研究所，保藏日期：2020年12月05日；保藏编号：CGMCC No.21109；分类命名：长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis))。用补充了1％半胱氨酸的MRS培养基来培养受试的益生菌，并在37℃厌氧环境中孵育过夜。收获菌体并用生理盐水溶液冲洗，调整益生菌浓度将其接种在含有线虫生长培养基的平皿中，每个培养皿平板中益生菌为1×10 8CFU或1×10 7CFU。
本发明中所用HMO原料均来自于Jennewein。用蒸馏水配置母乳低聚糖溶液。
线虫感染模型
获取了年龄一致的线虫并将其培养在含线虫琼脂培养基(NGM培养基，线虫培养基中含有大肠杆菌OP50为食物)的培养皿中，添加了不同剂量的HMO(15mg/mL)与益生菌(1×10 8CFU、1×10 7CFU)组合物进行共培养(每个线虫培养皿中加入的液体总体积是10mL。对于浓度为15mg/mL的HMO受试组，每个培养皿中HMO的最终量是150mg。因此每个培养皿平板中，益生菌与HMO的添加量比例为：1×10 8CFU：150mg，或1×10 7CFU：150mg)。在线虫成年后，它们被转移到接种了金黄色葡萄球菌ATCC25923的培养皿中，添加量为10 8～10 9CFU/mL，来模拟受到金黄色葡萄球菌感染的情况。各组别在感染阶段添加的干预物(益生菌和/或HMO)情况分别与培养阶段相同。使用了两个对照，分别是没有致病菌的条件(线虫培养皿中含有大肠杆菌OP50)，以及有致病菌金黄色葡萄球菌感染但没有任何干预物的(只含有金黄色葡萄球菌的培养皿)。另设置培养阶段添加干预物而感染阶段没有任何干预物的组别、以及培养阶段未添加干预物而感染阶段添加干预物的组别。
将线虫培养几天后，对它们的存活率进行每日计数。如果线虫对铂丝没有反应，则可被认为是死亡。每种条件均进行了两次独立测定。
对存活曲线进行了统计学的比较分析，用GraphPad Prism 4统计学软件包进行了log rank survival显著性分析。用One-way ANOVA分析在感染第三天存活率的显著性差异。对各组在每一天的存活率数据，用Two-way ANOVA进行了统计分析，并用Dunnett’posthoc test进行了显著性分析。
实施例1：母乳低聚糖与益生菌YLGB-1496组合物对秀丽隐杆线虫受到金黄色 葡萄球菌感染时存活率的影响
如图1所示，15mg/mL的HMO 2’-FL与YLGB-1496(10 8CFU)对于线虫受到金黄色葡萄球菌的感染情况下的存活率，都起到了显著的保护与提升作用(P<0.0001)，并且二者的保护作用是比较相近的。当2’-FL与YLGB-1496菌株(10 8CFU)形成组合物，这种情况下对于线虫受到金葡菌感染时的存活率的提升作用，比单独的这两种物质，即单独菌株或者单独HMO，效果都显著更好，且组合物相比单独的原料，实现了22％的存活率提升(P<0.001)。可见当2’-FL与YLGB-1496形成组合物，二者体现了较好的协同效应。
实施例2：添加的母乳低聚糖组合与长双歧杆菌婴儿亚种YLGB-1496组合物的 配方粉
本实施例提供一种婴儿配方奶粉，该配方奶粉中总蛋白质含量为11.1g/100g粉，脂肪含量为28.3g/100g粉，碳水化合物含量为52.9g/100g粉，母乳低聚糖2’-FL含量1.5g/100g粉，长双歧杆菌婴儿亚种YLGB-1496为1×10 8CFU/100g粉。

Claims (15)

  1. 一种益生元与益生菌的组合物在制备食品或药品中的应用，其中，所述益生元包括母乳低聚糖，所述益生菌包括长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)，所述食品或药品是用于以下至少一种功效的食品或药品：
    提升生物体对金黄色葡萄球菌感染的抵御能力；
    提高生物体先天免疫；和/或
    抗衰老特别是抗免疫衰老。
  2. 根据权利要求1所述的应用，其中，所述长双歧杆菌婴儿亚种包括保藏编号为CGMCC No.21109的菌株。
  3. 根据权利要求1或2所述的应用，其中，所述母乳低聚糖包括2’-岩藻糖基乳糖、3’-岩藻糖基乳糖、乳糖-N-四糖、3’-唾液酸基乳糖、6’-唾液酸基乳糖中的一种或多种；
    优选地，所述母乳低聚糖包括岩藻糖基低聚糖、唾液酸基低聚糖、N-乙酰化低聚糖中的至少一种；
    进一步地，优选为岩藻糖基低聚糖；优选为2’-岩藻糖基乳糖、3’-岩藻糖基乳糖；和/或，
    优选为N-乙酰化低聚糖；优选为乳糖-N-四糖、乳糖-N-新四糖；和/或，
    优选为唾液酸基低聚糖，优选为3’-唾液酸基乳糖、6’-唾液酸基乳糖中的一种或多种；
    更优选地，所述母乳低聚糖包括2’-岩藻糖基乳糖。
  4. 根据权利要求1或2所述的应用，其中，所述益生元与益生菌的组合物中，长双歧杆菌婴儿亚种与母乳低聚糖的比例为1×10 3CFU～1×10 12CFU：0.1g～10g，优选为1×10 6CFU～1×10 10CFU：1g～10g。
  5. 根据权利要求1所述的应用，其中，所述提升生物体对金黄色葡萄球菌感染抵御能力包括：提升个体预防金黄色葡萄球菌感染的能力，降低金黄色葡萄球菌感染个体的能力，和/或缓解金黄色葡萄球菌感染引起的个体食物中毒、肠炎、肺炎、皮肤感染、伤口溃烂和/或脑膜炎。
  6. 根据权利要求1所述的应用，其中，所述食品为液体饮料、固体饮料、口服液、奶制品、片剂或胶囊。
  7. 根据权利要求1所述的应用，其中，所述食品为乳粉，例如非婴幼儿乳粉或婴幼儿配方粉。
  8. 根据权利要求1或6或7所述的应用，其中，所述长双歧杆菌婴儿亚种在食品或药品中的应用量为1×10 3CFU/天～1×10 12CFU/天，优选为1×10 6CFU/天～1×10 11CFU/天；和/或
    所述母乳低聚糖在食品或药品中的应用量为0.015g/天～15g/天，进一步优选为0.1g/天～12g/天，更优选为1.5g/天～10g/天。
  9. 一种组合物，包括长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)和母乳低聚糖，所述母乳低聚糖包括2’-岩藻糖基乳糖、3’-岩藻糖基乳糖、乳糖-N-四糖、3’-唾液酸基乳糖、6’-唾液酸基乳糖中的一种或多种；
    优选地，所述母乳低聚糖包括2’-岩藻糖基乳糖；
    优选地，所述长双歧杆菌婴儿亚种包括保藏编号为CGMCC No.21109的菌株。
  10. 一种食品，其中包含有长双歧杆菌婴儿亚种与母乳低聚糖，其中：
    所述长双歧杆菌婴儿亚种在食品中的应用量为1×10 3CFU/天～1×10 12CFU/天，更优选为1×10 6CFU/天～1×10 11CFU/天；
    优选地，所述母乳低聚糖在食品中的应用量为0.015g/天～15g/天，进一步优选为0.1g/天～12g/天，更优选为1.5g/天～10g/天；
    优选地，所述食品是用于以下至少一种功效的食品：
    提升生物体对金黄色葡萄球菌感染的抵御能力；
    提高生物体先天免疫；和/或
    抗衰老特别是抗免疫衰老。
  11. 母乳低聚糖在用于提升长双歧杆菌婴儿亚种在提升生物体对金黄色葡萄球菌感染的抵御能力、提高生物体先天免疫和/或抗衰老方面的用途。
  12. 一种提升生物体对金黄色葡萄球菌感染的抵御能力、提高生物体先天免疫和/或抗衰老的方法，该方法包括给予有需要的生物体有效量的益生元与益生菌的组合物，其中，所述益生元包括母乳低聚糖，所述益生菌包括长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)。
  13. 根据权利要求12所述的方法，其中，所述抗衰老为抗免疫衰老。
  14. 根据权利要求12所述的方法，其中，所述长双歧杆菌婴儿亚种包括保藏编 号为CGMCC No.21109的菌株。
  15. 根据权利要求12所述的方法，其中，所述长双歧杆菌婴儿亚种给予有需要的生物体的量为1×10 3CFU/天～1×10 12CFU/天，优选为1×10 6CFU/天～1×10 11CFU/天；和/或
    所述母乳低聚糖给予有需要的生物体的量为0.015g/天～15g/天，进一步优选为0.1g/天～12g/天，更优选为1.5g/天～10g/天。
PCT/CN2022/133820 2021-11-30 2022-11-23 可提升生物体对金黄色葡萄球菌感染抵御能力的益生元与益生菌组合物 WO2023098541A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202111447740.6 2021-11-30
CN202111447740.6A CN116195740A (zh) 2021-11-30 2021-11-30 可提升生物体对金黄色葡萄球菌感染抵御能力的益生元与益生菌组合物

Publications (1)

Publication Number Publication Date
WO2023098541A1 true WO2023098541A1 (zh) 2023-06-08

Family

ID=86515181

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/133820 WO2023098541A1 (zh) 2021-11-30 2022-11-23 可提升生物体对金黄色葡萄球菌感染抵御能力的益生元与益生菌组合物

Country Status (2)

Country Link
CN (1) CN116195740A (zh)
WO (1) WO2023098541A1 (zh)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090098240A1 (en) * 2007-05-17 2009-04-16 The Regents Of The University Of California Human milk oligosaccharides to promote growth of beneficial gut bacteria
CN101909644A (zh) * 2007-12-17 2010-12-08 雀巢产品技术援助有限公司 在免疫妥协的个体中机会感染的预防
CN102511714A (zh) * 2011-12-21 2012-06-27 浙江康恩贝健康产品有限公司 一种适合婴幼儿的高活性益生菌组合物及制备方法
CN112167346A (zh) * 2019-07-05 2021-01-05 内蒙古伊利实业集团股份有限公司 用以抗氧化的含乳酸菌菌株的食品组合物以及医药组合物
CN112515170A (zh) * 2019-11-29 2021-03-19 内蒙古伊利实业集团股份有限公司 提高胃肠道免疫能力的乳双歧杆菌与益生元组合物及应用
CN112868800A (zh) * 2019-11-29 2021-06-01 内蒙古伊利实业集团股份有限公司 含母乳低聚糖提高免疫力的婴幼儿配方奶粉及其制备方法
CN113491289A (zh) * 2020-04-03 2021-10-12 内蒙古伊利实业集团股份有限公司 可提升生物体对金黄色葡萄球菌感染的抵御能力的母乳低聚糖

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090098240A1 (en) * 2007-05-17 2009-04-16 The Regents Of The University Of California Human milk oligosaccharides to promote growth of beneficial gut bacteria
CN101909644A (zh) * 2007-12-17 2010-12-08 雀巢产品技术援助有限公司 在免疫妥协的个体中机会感染的预防
CN102511714A (zh) * 2011-12-21 2012-06-27 浙江康恩贝健康产品有限公司 一种适合婴幼儿的高活性益生菌组合物及制备方法
CN112167346A (zh) * 2019-07-05 2021-01-05 内蒙古伊利实业集团股份有限公司 用以抗氧化的含乳酸菌菌株的食品组合物以及医药组合物
CN112515170A (zh) * 2019-11-29 2021-03-19 内蒙古伊利实业集团股份有限公司 提高胃肠道免疫能力的乳双歧杆菌与益生元组合物及应用
CN112868800A (zh) * 2019-11-29 2021-06-01 内蒙古伊利实业集团股份有限公司 含母乳低聚糖提高免疫力的婴幼儿配方奶粉及其制备方法
CN113491289A (zh) * 2020-04-03 2021-10-12 内蒙古伊利实业集团股份有限公司 可提升生物体对金黄色葡萄球菌感染的抵御能力的母乳低聚糖

Also Published As

Publication number Publication date
CN116195740A (zh) 2023-06-02

Similar Documents

Publication Publication Date Title
JP6985231B2 (ja) プレバイオティクスとしての、精製された２’−フコシルラクトース、３−フコシルラクトース、およびラクトジフコテトラオースの使用
EP4129302A1 (en) Breast milk oligosaccharides for improving resistance of organism against staphylococcus aureus infection
Pushpanathan et al. Gut microbiota and its mysteries
KR101095712B1 (ko) 점막 면역 부활 작용을 갖는 유산균
WO2023088290A1 (zh) 一种含乳双歧杆菌与母乳低聚糖的组合物及其应用
Edens An alternative for antibiotic se in poultry: probiotics
Griffiths et al. In vivo effects of bifidobacteria and lactoferrin on gut endotoxin concentration and mucosal immunity in Balb/c mice
CN102905712B (zh) 用于治疗肠炎的益生菌组合物
Cheng et al. The bidirectional relationship between host physiology and microbiota and health benefits of probiotics: A review
Heavey et al. The gut microflora of the developing infant: microbiology and metabolism
TW201302205A (zh) 預防急性呼吸道感染及／或緩解感染症狀之組合物
CN114223729B (zh) 长双歧杆菌婴儿亚种与母乳低聚糖组合物在配方奶粉中的应用
Pande et al. Prospectus of probiotics in modern age diseases
CN111528486A (zh) 一种含乳铁蛋白的组合物
WO2023098541A1 (zh) 可提升生物体对金黄色葡萄球菌感染抵御能力的益生元与益生菌组合物
CN114223728B (zh) 含有益生元与益生菌的早产/低出生体重婴儿配方奶粉
CN114504107B (zh) 一种含鼠李糖乳杆菌与母乳低聚糖的组合物及其应用
CN114504108B (zh) 一种含副干酪乳杆菌与母乳低聚糖的组合物及其应用
García-Elorriaga et al. Nutrition and intestinal microflora
KR102083470B1 (ko) 흑효모 발효 다당체를 유효성분으로 포함하는 장내 균총 개선 및 비만 예방, 치료용 조성물
CN113116938A (zh) 四联活菌制剂及其应用
Srivastava et al. ROLE OF PROBIOTICS IN CONTROL OF GASTROINTESTINAL DISEASES.
CN114568701B (zh) 含低聚果糖和益生菌的组合物及其应用
CN114431484A (zh) 人乳寡糖在提高肠道对沙门氏菌感染抵御能力中的应用
Mazzola The role of bifidobacteria in newborn health and the intestinal microbial balance

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22900346

Country of ref document: EP

Kind code of ref document: A1