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WO2025116013A1 - Composition pour lutter contre la prolifération de bactéries butyriques - Google Patents

Composition pour lutter contre la prolifération de bactéries butyriques Download PDF

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Publication number
WO2025116013A1
WO2025116013A1 PCT/JP2024/042331 JP2024042331W WO2025116013A1 WO 2025116013 A1 WO2025116013 A1 WO 2025116013A1 JP 2024042331 W JP2024042331 W JP 2024042331W WO 2025116013 A1 WO2025116013 A1 WO 2025116013A1
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Prior art keywords
kojibiose
bacteria
composition
information
faecalibacterium
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Japanese (ja)
Inventor
淳也 石田
愛弓 市川
紘生 根岸
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Meiji Co Ltd
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Meiji Co Ltd
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    • 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 OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/13—Fermented milk preparations; Treatment using microorganisms or enzymes using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a composition for controlling the growth of butyric acid bacteria, such as bacteria of the genus Faecalibacterium.
  • Faecalibacterium bacteria are one of the most common bacteria in the intestines of healthy adults, and have physiological functions that are favorable for human health, such as butyric acid production and anti-inflammatory activity. It has been reported that Faecalibacterium is reduced in the intestines of patients with inflammatory bowel diseases, including Crohn's disease and ulcerative colitis (Non-Patent Document 1). Similar reports have also been made of patients with asthma, food allergies, non-alcoholic fatty liver disease, and chronic kidney disease (Non-Patent Documents 2 to 6, respectively).
  • Faecalibacterium bacteria are reduced in the intestines of patients with irritable bowel syndrome (IBS) (Non-Patent Document 7), inflammatory bowel disease (IBD) (Non-Patent Document 8), Parkinson's disease (Non-Patent Document 9), and cancer (Non-Patent Document 10) compared to healthy individuals. It has also been reported that administering this bacterium to IBD model mice improves symptoms such as weight loss and diarrhea (Non-Patent Document 11), and that administering this bacterium to Alzheimer's disease model mice improves cognitive impairment (Non-Patent Document 12). Furthermore, it has been reported that Faecalibacterium prausnitzii exhibits anti-inflammatory effects in cultured cell lines and TNBS colitis model mice (Non-Patent Document 13).
  • Patent Document 2 describes an in vivo lipid regulator that contains one or more active ingredients selected from kojibiose, kojitriose, kojibiosyl glucoside, kojitetraose, and kojitriosyl glucoside.
  • Non-Patent Documents 15 and 16 it has been reported that kojibiose and 4'-galactosyl lactose do not inhibit the growth of Faecalibacterium prausnitzii in stool culture test systems.
  • Non-Patent Document 20 a study of various isomeric glucose disaccharides using a human colon batch fermentation model reported that fermentation of diglucose ⁇ (1-1) (trehalose) resulted in significantly higher butyrate production than other ⁇ -linked diglucoses, including kojibiose.
  • non-Patent Document 20 co-culture of Bifidobacterium adolescentis L2-32 with Faecalibacterium prausnitzii S3/L3 using fructooligosaccharides as the carbon source, and with F. prausnitzii A2-165 using starch as the carbon source, showed that the butyrate concentration was higher in the co-cultures than in the monocultures of F. prausnitzii (Non-Patent Document 21).
  • butyric acid is expected to have effects such as suppressing fatty liver and obesity (Non-Patent Documents 17, 18), and it has been reported that an increase in butyric acid in the intestine acts on immune control, such as suppressing inflammation through an increase in regulatory T cells (Non-Patent Document 19).
  • butyric acid has a characteristic unpleasant odor, it would be preferable to have a means of controlling butyric acid production in the intestine rather than directly ingesting it.
  • prebiotics to control the proliferation of butyric acid bacteria such as Faecalibacterium bacteria, in the intestine, it is expected that various diseases can be prevented and improved.
  • the present invention provides the following: [1] A composition for controlling the growth of butyric acid bacteria, comprising any one selected from kojibiose and oligosaccharides having kojibiose as a constituent sugar. [2] The composition described in 1, wherein the butyric acid bacteria are Faecalibacterium bacteria. [3] The composition according to 1 or 2, for use as a prebiotic or synbiotic.
  • a composition for treating any one selected from inflammation, asthma, food allergy, non-alcoholic fatty liver, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive decline, and atopic dermatitis comprising any one selected from kojibiose and oligosaccharides having kojibiose as a constituent saccharide.
  • a composition for controlling butyric acid production in the intestine comprising any one selected from kojibiose and oligosaccharides having kojibiose as a constituent sugar.
  • composition according to 6 wherein the control of butyric acid production is mediated by control of the proliferation of Faecalibacterium bacteria in the intestine.
  • composition according to any one of 1 to 12 wherein the composition contains, as one selected from kojibiose and oligosaccharides having kojibiose as a constituent saccharide, one having the ability to promote the growth of Parabacteroides.
  • composition according to any one of 1 to 13, comprising galactosyl kojibiose as the saccharide selected from kojibiose and oligosaccharides having kojibiose as a constituent saccharide.
  • the method for providing food information comprises: a step of acquiring information, in which information on the presence or absence or amount of Faecalibacterium bacteria is acquired from information on the intestinal bacterial flora; and a step of deriving food information, in which information on a food that is a composition containing any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent sugar is derived based on the information on the presence or absence or amount of Faecalibacterium bacteria.
  • a composition comprising any one selected from kojibiose and oligosaccharides having kojibiose as a constituent sugar, for use in a method for controlling the growth of butyric acid bacteria.
  • a method or non-therapeutic method for controlling the growth of butyric acid bacteria comprising the step of administering to a subject a composition comprising any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent sugar.
  • compositions comprising any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent sugar, for controlling the growth of butyric acid bacteria.
  • a composition comprising any one selected from kojibiose and oligosaccharides having kojibiose as a constituent saccharide, for use in a method for treating any one selected from inflammation, asthma, food allergies, non-alcoholic fatty liver, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive decline, and atopic dermatitis.
  • any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent saccharide in the manufacture of a composition for treating any one selected from inflammation, asthma, food allergies, non-alcoholic fatty liver, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive decline, and atopic dermatitis.
  • a method or non-therapeutic method for treating any one selected from inflammation, asthma, food allergies, non-alcoholic fatty liver, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive decline, and atopic dermatitis comprising the step of administering to a subject a composition containing any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent sugar.
  • compositions containing any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent sugar for treating any one selected from inflammation, asthma, food allergies, non-alcoholic fatty liver, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive decline, and atopic dermatitis.
  • a composition comprising any one selected from kojibiose and oligosaccharides having kojibiose as a constituent sugar for use in a method for controlling intestinal butyric acid production.
  • a method or non-therapeutic method for controlling intestinal butyric acid production comprising a step of administering to a subject a composition comprising any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent sugar.
  • compositions comprising any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent sugar for controlling intestinal butyric acid production.
  • a composition comprising any one selected from kojibiose and oligosaccharides having kojibiose as a constituent sugar, for use in a method for treating a disease or condition that can be improved by controlling the growth of intestinal Faecalibacterium bacteria.
  • a method or non-therapeutic method for treating a disease or condition that can be improved by controlling the growth of intestinal Faecalibacterium bacteria comprising the step of administering to a subject a composition comprising any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent sugar.
  • compositions comprising any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent sugar, for treating a disease or condition that can be improved by controlling the growth of intestinal Faecalibacterium bacteria.
  • a method for controlling the proliferation of Faecalibacterium bacteria in intestinal bacterial flora comprising a step of causing intestinal bacterial flora containing Faecalibacterium bacteria to contain any one selected from kojibiose and oligosaccharides having kojibiose as a constituent sugar.
  • butyric acid bacteria such as Faecalibacterium bacteria
  • Faecalibacterium bacteria By using kojibiose or any of the oligosaccharides whose constituent sugars are kojibiose as a prebiotic, it is possible to increase butyric acid bacteria, such as Faecalibacterium bacteria, in the intestines. Furthermore, by increasing the amount of butyric acid bacteria in the intestines, it is expected that various diseases can be prevented and improved.
  • This embodiment relates to a composition for controlling the growth of butyric acid bacteria, such as Faecalibacterium, that contains kojibiose and oligosaccharides having kojibiose as its constituent sugars as active ingredients.
  • butyric acid bacteria such as Faecalibacterium
  • the composition of the present embodiment contains, as an active ingredient, any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent saccharide.
  • any one is used to mean “at least one” unless otherwise specified.
  • any one selected from the group consisting of kojibiose and oligosaccharides having kojibiose as a constituent saccharide includes only kojibiose, only one type of oligosaccharide having kojibiose as a constituent saccharide, one type of oligosaccharide having kojibiose and kojibiose as a constituent saccharide, two types of oligosaccharides having kojibiose as a constituent saccharide, etc.
  • Constants as an active ingredient refers to the fact that the active ingredient is used in the composition in an effective amount to exert the intended function, that the active ingredient is specified by labeling as an ingredient that contributes to the intended purpose, and the like.
  • active ingredients are sometimes referred to as functional ingredients (ingredients that contribute to specific health purposes (excluding those related to reducing the risk of disease)).
  • the kojibiose and oligosaccharides having kojibiose as a constituent sugar used in the composition are not particularly limited as long as they have the intended effect.
  • the kojibiose and oligosaccharides having kojibiose as a constituent sugar used in the composition may be one type or a combination of two or more types.
  • oligosaccharides that contain kojibiose include the trisaccharides galactosyl kojibiose, kojitriose, selaginose (kojibiosylglucoside), centose, and kojibiosylfructoside, as well as tetrasaccharides in which one molecule of a monosaccharide such as glucose is bonded to each of these trisaccharides, such as kojitetraose and kojitriosylglucoside.
  • the composition contains either kojibiose or galactosyl kojibiose.
  • examples of such compositions include a composition containing kojibiose, a composition containing galactosyl kojibiose, a composition containing kojibiose and galactosyl kojibiose, and a composition containing kojibiose, galactosyl kojibiose, and a tetrasaccharide in which one glucose molecule is bound to galactosyl kojibiose.
  • galactosyl kojibiose refers to kojibiose in which galactose is ⁇ - or ⁇ -linked to any of positions 1 to 8 of the following kojibiose.
  • galactose can be linked to the OH at position 8 in four ways ( ⁇ - ⁇ , ⁇ - ⁇ , ⁇ - ⁇ , ⁇ - ⁇ ) and to the OH at positions 2 to 7 in two ways, so 18 types of galactosyl kojibiose are expected.
  • 8 ⁇ - ⁇ kojibiose 8 ⁇ - ⁇ kojibiose, 8 ⁇ - ⁇ kojibiose, 8 ⁇ - ⁇ kojibiose, 8 ⁇ - ⁇ kojibiose, 1 ⁇ kojibiose, 2 ⁇ kojibiose, 2 ⁇ kojibiose, 2 ⁇ kojibiose, 3 ⁇ kojibiose, 3 ⁇ kojibiose, 4 ⁇ kojibiose, 4 ⁇ kojibiose, 5 ⁇ kojibiose, 5 ⁇ kojibiose, 6 ⁇ kojibiose, 6 ⁇ kojibiose, 7 ⁇ kojibiose, and 7 ⁇ kojibiose, respectively.
  • the composition includes any one of the 18 types of galactosyl kojibiose, namely, 8 ⁇ - ⁇ kojibiose, 8 ⁇ - ⁇ kojibiose, 8 ⁇ - ⁇ kojibiose, 8 ⁇ - ⁇ kojibiose, 1 ⁇ kojibiose, 2 ⁇ kojibiose, 2 ⁇ kojibiose, 2 ⁇ kojibiose, 3 ⁇ kojibiose, 3 ⁇ kojibiose, 4 ⁇ kojibiose, 4 ⁇ kojibiose, 5 ⁇ kojibiose, 5 ⁇ kojibiose, 6 ⁇ kojibiose, 6 ⁇ kojibiose, 7 ⁇ kojibiose, and 7 ⁇ kojibiose, and may include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18.
  • the galactosyl kojibiose contained in the composition is ⁇ -D-glucopyranosyl-(1 ⁇ 2)-[ ⁇ -D-galactopyranosyl-(1 ⁇ 4)-]D-glucopyranoside.
  • This sugar can also be expressed as a type of glucosyl lactose.
  • galactosyl kojibiose has been confirmed to have an excellent effect of inhibiting the proliferation of Faecalibacterium bacteria, a type of butyric acid bacteria.
  • galactosyl kojibiose is a type of oligosaccharide that contains kojibiose as a constituent sugar, and after being administered to a subject, it can be broken down by lactase in the subject's digestive tract to produce kojibiose. Therefore, any sugar that contains kojibiose as a constituent sugar can similarly produce kojibiose in the intestines and exert the same effect as galactosyl kojibiose.
  • the composition contains either kojibiose or an oligosaccharide having kojibiose as a constituent sugar, and has the ability to promote the growth of Parabacteroides bacteria.
  • Parabacteroides bacteria are one of the bacteria that are most commonly present in the intestines of healthy adults. According to the inventors' study, when Faecalibacterium bacteria, a type of butyric acid bacteria, were cultured in the culture supernatant of Parabacteroides bacteria, the growth was promoted compared to when the bacteria were cultured in a fresh medium. Therefore, it can be said that the growth of butyric acid bacteria such as Faecalibacterium bacteria can be controlled through the growth of Parabacteroides bacteria. The inventors have separately confirmed that kojibiose and oligosaccharides containing kojibiose as a constituent sugar promote the growth of Parabacteroides bacteria (PCT/JP2023/030455). Furthermore, another experiment has suggested that the growth of Faecalibacterium can be controlled by promoting the growth of Parabacteroides bacteria (application in preparation).
  • kojibiose and oligosaccharides having kojibiose as a constituent sugar promote the growth of Parabacteroides bacteria.
  • Other oligosaccharides having kojibiose as a constituent sugar and promoting the growth of Parabacteroides bacteria can be identified according to the procedure for evaluating whether a certain component controls the growth of Faecalibacterium bacteria in the intestine, as described below.
  • the composition contains either kojibiose or an oligosaccharide having kojibiose as a constituent sugar, which promotes the growth of Parabacteroides bacteria selected from P. distasonis and P. merdae, preferably P. distasonis.
  • the kojibiose and oligosaccharides having kojibiose as a constituent sugar used in the present invention are not particularly limited in terms of origin or production method, and may be produced by any method, such as fermentation, enzymatic or organic synthesis.
  • One preferred production method includes a production method including a step of reacting a raw material composition containing lactose and sucrose with glucansucrase, or a lactic acid bacterium expressing glucansucrase, or a processed product thereof, to obtain a composition containing galactosyl kojibiose.
  • glucansucrase refers to an enzyme belonging to glycoside hydrolase (also called glycosyl hydrolases) family 70 (GH70), unless otherwise specified (see (CAZy) databases and Cantarel et al., Nucleic Acids Res. 37:D233-238, 2009).
  • glycoside hydrolase also called glycosyl hydrolases family 70 (GH70)
  • lactic acid bacteria When lactic acid bacteria are used, they are preferably lactic acid bacteria that express glucansucrase.
  • lactic acid bacteria include lactic acid bacteria belonging to the family Leuconostoc, more preferably lactic acid bacteria belonging to the genus Leuconostoc, and even more preferably Leuconostoc mesenteroides.
  • lactic acid bacteria When using lactic acid bacteria, it is preferable that the lactic acid bacteria constantly express glucansucrase.
  • lactic acid bacteria are lactic acid bacteria belonging to the Lactobacillaceae family, more preferably, lactic acid bacteria belonging to the Liquorilactobacillus genus or lactic acid bacteria belonging to the Limosilactobacillus genus, and even more preferably, Limosilactobacillus reuteri and Liquorilactobacillus satsumensis.
  • the lactic acid bacteria it is preferable that the lactic acid bacteria constantly express glucansucrase, and more preferably, the glucansucrase is of the cell-bound type.
  • a preferred example of lactic acid bacteria is a lactic acid bacteria belonging to the Lactobacillaceae family, more preferably, a lactic acid bacteria belonging to the Liquorilactobacillus genus, and even more preferably, Liquorilactobacillus satsumensis.
  • a particularly preferred example of Liquorilactobacillus satsumensis strain is JCM12392. Note that JCM12392 is written as Lactobacillus satsumensis in RIKEN BioResource Center, GENERAL CATALOG No.9, 2012, JAPAN COLLECTION OF MICROORGANISMS, M51.
  • the lactic acid bacteria expressing glucansucrase or a processed product thereof is preferably any one selected from the group consisting of live bacteria, killed bacteria, a culture containing bacteria, a disrupted bacteria product, and a purified product of glucansucrase.
  • Glucansucrase or lactic acid bacteria expressing glucansucrase, or processed products thereof, used for producing kojibiose and oligosaccharides having kojibiose as a constituent sugar can be produced using transformation, chemical synthesis, or genome editing techniques.
  • the composition containing galactosyl kojibiose obtained by such a production method can be used as it is as a solution containing kojibiose and oligosaccharides whose constituent sugars are kojibiose, or after purification with an ion exchange resin or the like.
  • the composition of the present invention may be a composition containing galactosyl kojibiose obtained by acting a composition containing sucrose and lactose with glucansucrase, or a lactic acid bacterium expressing glucansucrase, or a processed product thereof.
  • the composition of the present embodiment can be used to control the growth of butyric acid bacteria.
  • butyric acid bacteria are good bacteria (bacteria useful for health) that can produce butyric acid in the intestine.
  • Butyric acid bacteria are also called butyrate-producing bacteria.
  • the composition can be used to control the growth of butyric acid bacteria in the human intestine. Controlling the growth of butyric acid bacteria in the human intestine refers to controlling the growth of butyric acid bacteria in a state in which various bacteria living in the human intestine are present (sometimes referred to as intestinal flora).
  • intestinal flora refers to a flora in which various bacteria living in the intestine are present, including, for example, a flora contained in feces, and is not limited to a flora in the intestine.
  • control includes upward control (sometimes referred to as promotion or increase) and downward control (sometimes referred to as suppression or decrease), and is preferably upward control.
  • the control of growth can be the control of the number of bacteria or the control of the occupancy rate described later.
  • the intestine refers to the digestive organ in humans and animals where bacteria reside and which digests and absorbs ingested food.
  • the intestine includes the small intestine and large intestine, and is preferably the large intestine.
  • the composition is used to control the proliferation of any of the butyric acid bacteria selected from the group consisting of bacteria belonging to the genus Faecalibacterium, bacteria belonging to the genus Coprococcus, bacteria belonging to the genus Clostridium, bacteria belonging to the genus Eubacterium, bacteria belonging to the genus Roseburia, bacteria belonging to the genus Butyrivibrio, bacteria belonging to the genus Anaerostipes, bacteria belonging to the genus Subdoligranulum, bacteria belonging to the genus Anaerotruncus, bacteria belonging to the genus Ruminococcus, bacteria belonging to the genus Shuttleworthia, bacteria belonging to the genus Lachnospira, bacteria belonging to the genus Megasphaera, and bacteria belonging to the genus Butyricicoccus.
  • the butyric acid bacteria selected from the group consisting of bacteria belonging to the genus Faecalibacterium, bacteria belonging to the genus Coprococcus, bacteria belonging to the genus Clos
  • the composition is used to control the growth of any selected from the following bacteria, which are the major strains of Clostridium butyricum isolated from the human large intestine: Faecalibacterium prausnitzii, Faecalibacterium longum, Faecalibacterium butyricigenerans, Faecalibacterium hattorii, Faecalibacterium duncaniae, Eubacterium lomosum, Eubacterium rectale, Roseburia intestinalis, Roseburia faecis, Roseburia hominis, Roseburia inulinivorans, Roseburia ceccicola, Butyrivibrio fibrisolvens, Butyrivibrio crossotus, Butyrivibrio proteoclasticus, Eubacterium ramulus, Eubacterium hallii, Anaerostipes caccae, Anaerostipes butyraticus, Anaerostipes handrus, Anaerostipes rhamnosivorans, SSC/2, SS
  • the composition is used to control the proliferation of bacteria belonging to the genus Faecalibacterium (sometimes simply referred to as Faecalibacterium bacteria) in the intestine.
  • Faecalibacterium bacteria sometimes simply referred to as Faecalibacterium bacteria
  • the present invention, embodiments, and examples will be explained using Faecalibacterium bacteria as an example of butyric acid bacteria, but those skilled in the art will be able to understand and apply the explanation to other butyric acid bacteria as well.
  • Faecalibacterium bacteria examples include: Faecalibacterium prausnitzii; Faecalibacterium duncaniae Faecalibacterium longum Faecalibacterium butyricigenerans Faecalibacterium hattorii, The Faecalibacterium bacterium is preferably Faecalibacterium prausnitzii.
  • Faecalibacterium bacteria refers to bacteria that are identified as belonging to the genus Faecalibacterium by molecular phylogenetic analysis based on the 16S rRNA gene.
  • the criteria for determining genera by molecular phylogenetic analysis based on the 16S rRNA gene are well known to those skilled in the art (Stackebrandt E, Ebers J. Taxonomic parameters revisited: tarnished gold standards. Microbiol Today 2006;33:152-155.).
  • controlling the proliferation of a specific bacterium in a bacterial flora means controlling the proportion (occupancy rate) of the specific bacterium in the bacterial flora.
  • Faecalibacterium bacteria in the intestine can be evaluated as follows: Feces containing Faecalibacterium bacteria provided by a healthy individual is added to an appropriate culture medium and, if necessary, cultivated for a certain period of time. After that, the component to be evaluated is added and cultivated under appropriate conditions (e.g., cultivation for 48 hours at 37°C under anaerobic conditions, which are similar to the conditions in the intestine). The number of Faecalibacterium bacteria in the bacterial flora in the culture is then measured. The measurement results can then be compared with those of a culture cultivated under identical conditions, except that a control (e.g., sterilized water) has been added instead of the component to be evaluated, to make a judgment.
  • a control e.g., sterilized water
  • the number of bacteria of the genus Faecalibacterium contained in the bacterial flora can be determined by a known method.
  • One of the preferred methods is to perform 16S metagenomic analysis (sequence analysis of 16S rRNA gene amplicon) on DNA extracted from the culture.
  • DNA can be extracted using a commercially available kit.
  • the genomic region to be analyzed is not particularly limited as long as it can identify bacteria, but the V3-V4 region of the 16S rRNA gene can be used. Methods such as primers, amplification conditions, and amplicon purification for analyzing bacteria can also be methods well known to those skilled in the art. It is preferable to decipher the sequence using a next-generation sequencer with higher performance.
  • a next-generation microbiome bioinformatics platform such as QIIME 2 TM can be used to analyze the obtained data.
  • QIIME 2 TM can be used to analyze the obtained data.
  • 16S metagenomic analysis those skilled in the art can refer to information such as Sanschagrin S, Yergeau E. Next-generation sequencing of 16S ribosomal RNA gene amplicons. J Vis Exp. 2014;(90):51709. Published 2014 Aug 29. doi:10.3791/51709.
  • the composition can be used for the treatment of any of inflammation, asthma, food allergies, non-alcoholic fatty liver disease, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive decline, and atopic dermatitis.
  • the treatment is not limited to those mediated by controlling the proliferation of Faecalibacterium bacteria in the intestine, unless otherwise specified.
  • Faecalibacterium bacteria are one of the bacteria most commonly found in the intestines of healthy adults, and have physiological functions that are favorable for human health, such as butyric acid production and anti-inflammatory activity. It has also been reported that Faecalibacterium is reduced in the intestines of patients with inflammatory bowel diseases, including Crohn's disease and ulcerative colitis (Non-Patent Document 1). Similar reports have also been made of patients with asthma, food allergies, non-alcoholic fatty liver disease, and chronic kidney disease (Non-Patent Documents 2 to 6, respectively).
  • Faecalibacterium bacteria are reduced in the intestines of patients with irritable bowel syndrome (IBS) (Non-Patent Document 7), inflammatory bowel disease (IBD) (Non-Patent Document 8), Parkinson's disease (Non-Patent Document 9), and cancer (Non-Patent Document 10) compared to healthy individuals. It has also been reported that administering Faecalibacterium prausnitzii to IBD model mice improves symptoms such as weight loss and diarrhea (Non-Patent Document 11), and that administering Faecalibacterium prausnitzii to Alzheimer's disease model mice improves cognitive impairment (Non-Patent Document 12).
  • the composition can be used for treating inflammation in the intestine through growth control of Faecalibacterium bacteria in the intestine, and in another embodiment, the composition can be used for treating Crohn's disease and inflammatory bowel disease through growth control of Faecalibacterium bacteria in the intestine.
  • Inflammatory bowel disease includes ulcerative colitis and Crohn's disease.
  • the composition can be used to treat any disease or condition selected from asthma, food allergies, non-alcoholic fatty liver disease, chronic kidney disease, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), Parkinson's disease, cancer, symptoms associated with IBD such as weight loss and diarrhea, cognitive impairment in Alzheimer's disease, and inflammation, through growth control of Faecalibacterium bacteria in the intestine.
  • any disease or condition selected from asthma, food allergies, non-alcoholic fatty liver disease, chronic kidney disease, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), Parkinson's disease, cancer, symptoms associated with IBD such as weight loss and diarrhea, cognitive impairment in Alzheimer's disease, and inflammation, through growth control of Faecalibacterium bacteria in the intestine.
  • the composition can be configured to be free of any of the following: Oligosaccharides (e.g., raffinose, stachyose, galactooligosaccharides, isomaltooligosaccharides, lactofructose oligosaccharides, lactulose, xylooligosaccharides, agarooligosaccharides, mannooligosaccharides, or fructooligosaccharides), inulin, pectin, processed pectin, guar gum, decomposed guar gum, psyllium seed gum, karaya gum, tragacanth gum, gum arabic, resistant starch, resistant dextrin, polydextrose, cellulose, hemicellulose, soybean polysaccharides, ⁇ -glucan, glucomannan, galactomannan, chondroitin sulfate, hyal
  • Oligosaccharides e.g., raffin
  • the composition When used for anti-inflammatory purposes or for treating inflammatory bowel disease, the composition contains as an active ingredient any one selected from sugar acid-containing oligosaccharides and salts thereof, and may not contain any other oligosaccharides.
  • the composition can also be used to treat diseases or conditions that can be improved by controlling the proliferation of Faecalibacterium bacteria in the intestine. There can be a variety of such diseases or conditions.
  • composition of this embodiment can also be used to control butyric acid production in the intestine, and preferably to promote butyric acid production.
  • the composition controls butyric acid production through controlling the proliferation of Faecalibacterium bacteria in the intestine.
  • Whether or not a certain component can control butyrate production in the intestine can be determined by measuring the butyrate concentration in feces provided by healthy individuals who have ingested the component, and comparing it with an appropriate control if necessary.
  • feces provided by healthy individuals can be added to an appropriate culture medium, and after culturing for a certain period of time if necessary, the component to be evaluated is added and cultured under appropriate conditions (e.g., culturing for 48 hours at 37 °C under anaerobic conditions, similar to the conditions in the intestine). The butyrate concentration in the culture is then measured.
  • the measurement results can then be compared with the measurement results for a culture cultured under the same conditions except for the addition of a control (e.g., sterile water, or something that clearly does not control butyrate production) instead of the component to be evaluated, to determine whether or not the butyrate in the sample can be measured.
  • a control e.g., sterile water, or something that clearly does not control butyrate production
  • the means for measuring butyrate in the sample can be determined appropriately depending on the sample and butyrate concentration, and can be measured by, for example, HPLC, gas chromatography, etc.
  • Butyric acid is one of the short-chain fatty acids present in the intestine. Butyric acid is expected to have effects such as suppressing fatty liver and obesity (Non-Patent Documents 17 and 18). It has also been reported that an increase in butyric acid in the intestine acts on immune control, such as inflammation suppression via an increase in regulatory T cells (Non-Patent Document 19). Therefore, the composition of the present invention can be used to treat diseases or conditions that can be prevented or improved by increasing butyric acid in the intestine, or diseases or conditions caused by a decrease in butyric acid in the intestine, and can also be used for suppressing fatty liver, obesity, and immune control.
  • treatment when referring to a disease or condition, the term "treatment” includes reducing the risk of onset, delaying onset, prevention, treatment, and halting or delaying progression. Treatment also includes maintaining a normal or desirable state, maintaining ability, and alleviating symptoms (preferably temporary alleviation of symptoms). Treatment further includes helping to improve from a disease or condition, alleviating a disease or condition, and reducing the risk of developing a disease or condition. Treatment includes radical treatment (treatment to remove the cause) and symptomatic treatment (treatment to improve symptoms).
  • Actions for improvement or treatment include medical actions performed by doctors and nurses and midwives under the instructions of doctors, as well as non-therapeutic actions performed by persons other than doctors, such as pharmacists, nutritionists (including registered dietitians and sports nutritionists), public health nurses, midwives, nurses, clinical laboratory technicians, sports instructors, pharmaceutical manufacturers, pharmaceutical distributors, food manufacturers, food distributors, etc. Also includes subjects who are suggested to take foods, beverages, or medicines that can control Fusobacterium bacteria based on the judgment of a computer program. Furthermore, prevention or reduction of the risk of developing the disease includes recommending the intake of certain foods and providing nutritional guidance (including nutritional guidance necessary for the medical treatment of injured or sick persons, and nutritional guidance for maintaining and promoting health).
  • composition of this embodiment is suitable for administration to subjects for whom it is desirable or necessary to control the proliferation of butyric acid bacteria, preferably Faecalibacterium bacteria, in the intestine; subjects for whom it is desirable or necessary to control butyric acid production in the intestine; subjects with a disease or condition that can be prevented or improved by increasing butyric acid in the intestine; subjects with a disease or condition caused by a decrease in butyric acid in the intestine; subjects with fatty liver or at risk thereof; obese subjects or at risk of obesity; subjects for whom it is desirable or necessary to regulate immunity; subjects for whom it is desirable or necessary to perform anti-inflammatory treatment in the intestine; subjects with inflammatory bowel disease or at risk thereof; and subjects with a disease or condition that can be improved by controlling the proliferation of Faecalibacterium bacteria in the intestine.
  • butyric acid bacteria preferably Faecalibacterium bacteria
  • Faecalibacterium bacteria examples include those with inflammatory bowel disease, those with allergies (asthma), those with food allergies, those with non-alcoholic fatty liver, those with chronic kidney disease, and those with dementia.
  • Subjects for which it is desirable or necessary to control the proliferation of intestinal butyric acid bacteria, preferably Faecalibacterium bacteria include subjects in which intestinal butyric acid bacteria, preferably Faecalibacterium bacteria, are detected in at least one of the intestine and stool, or in which the amount of butyric acid in the intestine is relatively low.
  • subjects for whom it is desirable or necessary to control the proliferation of butyric acid bacteria, preferably Faecalibacterium bacteria, in the intestine include subjects who have been found to have a relatively low number or occupancy rate of butyric acid bacteria, preferably Faecalibacterium bacteria, in the intestine, or a relatively low amount of butyric acid in the intestine, as determined by any test or analysis, such as an intestinal flora test, a test for substances in feces, or a fecal metabolome analysis; subjects who have been found to have a high risk of any of the following conditions selected from inflammation, asthma, food allergies, non-alcoholic fatty liver disease, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive decline, and atopic dermatitis; and subjects who have been recommended to take a food, drink, or medicine that controls the proliferation of butyric acid bacteria, preferably Faecalibacterium bacteria, in the intestine, based on the results of the test or
  • Subjects in which a relatively low number or occupancy rate of Faecalibacterium bacteria has been detected in at least one of the intestines and feces include, for example, cases in which, when a culture solution containing stool collected from a subject is cultured at 37°C under anaerobic conditions for 24 hours, the occupancy rate of Faecalibacterium bacteria in the culture solution is 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, or 0.3% or less.
  • the subject is healthy (not diagnosed with a disease by a physician).
  • the subject may be a human or a non-human animal.
  • the age of the subject is not particularly limited, and the subject may be, for example, a newborn (within 28 days of birth); an infant (less than 1 year of age); a toddler (1-6 years of age); a child (7 years of age or older, but under 15 years of age); an adult (15 years of age or older); or a person aged 65 years or older.
  • composition of the present invention can be a food composition or a pharmaceutical composition.
  • Food and pharmaceutical products include not only those for humans but also those for animals other than humans, unless otherwise specified.
  • Food includes general food, functional food, nutritional composition, and also therapeutic food (for the purpose of treatment. Prepared based on a menu prepared by a nutritionist or the like according to a doctor's meal prescription), dietary therapy food, ingredient-adjusted food, nursing care food, and food for medical support, unless otherwise specified.
  • Food includes not only solid food but also liquid food, such as beverages, energy drinks, liquid food, and soup, unless otherwise specified.
  • Functional foods refer to foods that can impart a certain functionality to a living body, and include, for example, foods for specified health uses (including conditionally designated health foods [specified health foods]), functional foods, health functional foods including foods with nutritional functions, foods for special dietary uses, dietary supplements, dietary supplements, supplements (for example, tablets, coated tablets, sugar-coated tablets, enteric preparations, capsules (enteric soft capsules, enteric hard capsules, colon delivery capsules, etc.), liquids, and other various dosage forms), dietary supplements, food supplements, medical foods (following the definition of the Food and Drug Administration (FDA)), beauty foods (for example, diet foods), and other health foods in general.
  • foods for specified health uses including conditionally designated health foods [specified health foods]
  • functional foods including foods with nutritional functions, foods for special dietary uses
  • dietary supplements for example, tablets, coated tablets, sugar-coated tablets, enteric preparations, capsules (enteric soft capsules, enteric hard capsules, colon delivery capsules, etc.), liquids, and other various dosage forms
  • the term "functional foods” includes health foods to which a health claim based on the food standards of Codex (the Joint FAO/WHO Food Standards Commission) is applied.
  • Food supplements are supplements to normal meals and are concentrated with nutrients or other substances that have nutritional or physiological effects, either alone or in combination, and are labeled as "Food Supplement” on the product.
  • a dietary supplement is a product (excluding tobacco) intended to supplement the diet, which contains one or more of the targeted ingredients and is labeled as a dietary supplement.
  • the composition may also be a refined product of a specific sugar. Refined products include fractions, partially refined products, and crude refined products. When actually labeling food products, the labeling laws of each country must be followed.
  • composition of the present invention may be administered orally, parenterally, for example, through a tube (gastrostomy, enterostomy), or nasally, but is preferably administered orally.
  • administration is used not only when a pharmaceutical product is administered to a subject, but also when a food other than a pharmaceutical product is ingested by a subject.
  • administer can be read as "intake”
  • administer can be read as "administer.”
  • the composition can be administered to a subject repeatedly, and can be administered to a subject continuously for an extended period of time.
  • the period is not particularly limited, but in order to fully demonstrate the effect, it is preferable to administer the composition continuously for a relatively long period of time, for example, 3 days or more, 1 week or more, 2 weeks or more, 1 month or more, 3 months or more, 6 months or more, or 1 year or more.
  • the composition may be administered routinely, proactively, such as when there is a high risk, or when the need arises.
  • the composition may be administered with a meal, before, after, or between meals, or at the onset of the disease or condition that it is desired to ameliorate with the composition.
  • the active ingredient kojibiose or any one selected from oligosaccharides having kojibiose as a constituent sugar can be used in an amount acceptable for food or medicine.
  • the dosage of the composition of this embodiment may be any amount that exerts the desired effect.
  • the dosage can be appropriately set in consideration of various factors such as the age, weight, and symptoms of the subject.
  • the daily dosage of the composition may be an amount acceptable for use as a food or pharmaceutical, and may be 0.5 g or more, 1 g or more, preferably 2 g or more, preferably 3 g or more, more preferably 5 g or more, and even more preferably 10 g or more, in terms of the amount of active ingredient.
  • the upper limit of the amount of active ingredient per day, whatever the lower limit, may be 80 g or less, 70 g or less, 60 g or less, 50 g or less, 40 g or less, 30 g or less, 20 g or less, or 15 g or less.
  • the amount of active ingredient refers to the total amount of active ingredients contained.
  • Dosage may be once a day or multiple times a day, for example 2 to 10 times.
  • the amount of active ingredient per dose may be, for example, 0.5 g or more, 1 g or more, preferably 2 g or more, more preferably 3 g or more, and even more preferably 5 g or more.
  • the upper limit of the amount of active ingredient per dose, whatever the lower limit, may be 70 g or less, 60 g or less, 50 g or less, 40 g or less, 30 g or less, 25 g or less, or 10 g or less.
  • the content of the active ingredient in the composition may be an amount acceptable for use as a food or medicine, and may be set appropriately depending on the form of the composition.
  • the content of the active ingredient per 100 g of the composition may be 0.01% or more, preferably 0.1% or more, more preferably 0.3% or more, and even more preferably 0.5% or more.
  • the upper limit of the active ingredient per 100 g of the composition may be 8% or less, 5% or less, 4% or less, or even 3% or less.
  • the content of the active ingredient per solid content of the composition may be 0.1% or more, preferably 1% or more, more preferably 3% or more, and even more preferably 5% or more.
  • the upper limit of the active ingredient per solid content may be 80% or less, 50% or less, 40% or less, or 30% or less.
  • % means % by mass, unless otherwise specified.
  • the composition may contain other active ingredients or nutritional ingredients that are acceptable as foods or pharmaceuticals.
  • ingredients include lipids (e.g., milk fat, vegetable oils and fats, oils and fats containing medium-chain fatty acids), proteins (e.g., milk proteins, milk protein concentrates (MPC), whey protein concentrates (WPC), whey protein isolates (WPI), ⁇ -lactalbumin ( ⁇ -La), ⁇ -lactoglobulin ( ⁇ -Lg), heat-denatured whey proteins, and enzyme-treated whey proteins), amino acids (e.g., lysine, arginine, glycine, alanine, glutamic acid, leucine, isoleucine, valine), kojibiose, and sugars containing kojibiose as a constituent sugar.
  • lipids e.g., milk fat, vegetable oils and fats, oils and fats containing medium-chain fatty acids
  • proteins e.g., milk proteins, milk protein concentrate
  • suitable nutrients include carbohydrates other than oligosaccharides (glucose, sucrose, fructose, maltose, trehalose, erythritol, maltitol, palatinose, xylitol, dextrin), electrolytes (e.g., sodium, potassium, calcium, magnesium), vitamins (e.g., vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, biotin, folic acid, pantothenic acid, and nicotinic acids), minerals (e.g., copper, zinc, iron, cobalt, manganese), antibiotics, and dietary fiber.
  • carbohydrates other than oligosaccharides e.g., sucrose, fructose, maltose, trehalose, erythritol, maltitol, palatinose, xylitol, dextrin
  • electrolytes e.g., sodium, potassium, calcium,
  • the composition may contain a prebiotic other than the active ingredient.
  • Prebiotics can be defined as indigestible food ingredients that have a beneficial effect on the host and improve the host's health by selectively altering the growth and activity of specific bacteria in the large intestine.
  • the composition may contain one type or two or more types of prebiotics other than the active ingredient.
  • prebiotics other than the active ingredient there are no particular limitations on prebiotics other than the active ingredient, so long as they do not interfere with the effects of the active ingredient contained in the composition.
  • prebiotics other than the active ingredient include galactooligosaccharides, fructooligosaccharides (GF2, GF3, GF4), xylooligosaccharides, isomaltooligosaccharides, raffinose, lactulose, lactosucrose, soybean oligosaccharides, coffee oligosaccharides, dietary fiber, and gluconic acid.
  • composition can also be used as a synbiotic, and may contain probiotics in addition to the active ingredient.
  • Synbiotics are a combination of probiotics and prebiotics.
  • Probiotics can be defined as microorganisms that have a beneficial effect on the host when introduced into the intestine of the host in a live state.
  • probiotics there are no particular limitations on the probiotics, so long as they do not interfere with the effects of the active ingredients contained in the composition.
  • Certain lactic acid bacteria are known as examples of probiotics.
  • the composition may further contain additives that are acceptable for use as food or medicine.
  • additives include inert carriers (solid or liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coating agents, colorants, preservatives, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, flavors, acidulants, and natural products.
  • these include water, other aqueous solvents, pharma- ceutical acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymers, sodium alginate, dextrin, water-soluble dextran, water-soluble dextrin, corn starch, sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, petrolatum, paraffin, stearyl alcohol, stearic acid, magnesium stearate, precipitated calcium carbonate, talc, human serum albumin, mannitol, sorbitol, lactose, sucralose, lactose hydrate, candy powder, white sugar, stevia, aspartame, acesulfame potassium, citric acid, lactic acid, malic acid, tartaric acid, phosphoric acid, acetic acid, fruit juice, vegetable juice, vegetable
  • the food composition may be prepared in any form, such as a solid, liquid, mixture, suspension, powder, granule, paste, jelly, gel, capsule, etc.
  • the food composition according to the present invention may be in any form, such as a dairy product, a supplement (e.g., a tablet, a coated tablet, a sugar-coated tablet, an enteric coating, etc., a capsule (enteric soft capsule, enteric hard capsule, large intestine delivery capsule, etc.), a confectionery, a beverage, a drink, a seasoning, a processed food, a side dish, a soup, etc.
  • a dairy product e.g., a tablet, a coated tablet, a sugar-coated tablet, an enteric coating, etc., a capsule (enteric soft capsule, enteric hard capsule, large intestine delivery capsule, etc.)
  • a confectionery e.g., a beverage, a drink, a seasoning, a processed food, a side dish, a soup,
  • the composition according to the present invention may be in the form of a liquid food, a semi-liquid food, a jelly, a gel, a powder, a formula, a liquid formula, a powder or liquid milk for pregnant women and lactating women, a fermented milk, a bar, a mousse, a chocolate, a biscuit, an ice cream, a fermented milk, a lactic acid bacteria drink, a dairy drink, a milk drink, a soft drink, a fruit juice drink, a tablet, a cheese, a bread, a biscuit, a cracker, a pizza crust, a food for the sick, a nutritional food, a frozen food, a processed food, etc.
  • the formula may be in the form of granules, powder, paste, thickened liquid, etc., for mixing with beverages or foods.
  • the granules and powder may be in the form of cubes or sticks (each packaged in a single serving).
  • modified powdered milk refers to raw milk, cow's milk, special cow's milk, raw buffalo milk, or foods made from these ingredients, processed or used as the main ingredient, to which nutrients necessary for infants are added, and made into a powder, as defined in the "Ministerial Ordinance on the Compositional Standards, etc. of Milk and Dairy Products (hereinafter referred to as the "Ministerial Ordinance on Milk, etc.”).
  • modified liquid milk refers to raw milk, cow's milk, special cow's milk, raw buffalo milk, or foods made from these ingredients, processed or used as the main ingredient, to which nutrients necessary for infants are added, and made into a liquid, as defined in the Ministerial Ordinance on Milk, etc.
  • the pharmaceutical composition can be in any dosage form suitable for oral administration, such as solid preparations such as tablets, granules, powders, pills, and capsules, liquid preparations such as solutions, suspensions, and syrups, gels, and aerosols.
  • solid preparations such as tablets, granules, powders, pills, and capsules
  • liquid preparations such as solutions, suspensions, and syrups, gels, and aerosols.
  • the stage of blending the active ingredient in the production of the composition, can be appropriately selected.
  • the stage of blending is not particularly limited as long as it does not significantly impair the properties of the active ingredient.
  • the active ingredient can be blended by mixing it with the raw material.
  • the active ingredient can be added at the final stage of production to produce a composition containing the active ingredient.
  • the composition can be labeled with its intended use (application), and in another embodiment, the function of the composition or active ingredient or the usage based on the function is displayed. Examples of usage based on the function are as described above for the functions, actions, and effects.
  • the composition of the present invention can be labeled with the fact that it can be used as a prebiotic or as a synbiotic (a combination of probiotics and prebiotics). Note that a period such as "temporary" or "long-term” may be displayed at the beginning of each wording as appropriate.
  • the composition is labeled to recommend administration to a specific subject.
  • Examples of subjects to which the labeling is provided are as described above for subjects.
  • Display can be explicit or implicit.
  • An example of explicit display is a direct statement on a tangible object such as the product itself, packaging, container, label, tag, etc.
  • an example of implicit display includes advertising and promotional activities by place or means such as websites, storefronts, pamphlets, exhibitions, seminars such as media seminars, books, newspapers, magazines, television, radio, mail, email, and voice.
  • the recommendation to consume the composition is displayed personally.
  • a display can be made using a document (whether written or electronic) addressed to the subject, the subject's tablet, smartphone, personal computer, the subject's SNS, etc.
  • a display can be made together with the display of the results of any test or analysis, such as an intestinal flora test, a test of substances in the feces, and a fecal metabolome analysis, for the subject. It can also be used for precision nutrition (individualized nutrition, which refers to proposing appropriate meals (nutrition) according to an individual's constitution).
  • a food information providing device comprising: an information acquisition unit for acquiring information on the intestinal microbiota of a subject; A derivation unit that derives information on food to be provided to the subject based on the information on the intestinal flora; and a provision unit that provides the derived food information to the subject.
  • the information acquisition unit of the device acquires information on the presence or absence or amount of butyric acid bacteria from the intestinal bacterial flora information, and the derivation unit derives information on a food that is a composition containing either kojibiose or an oligosaccharide having kojibiose as a constituent sugar, based on the information on the presence or absence or amount of butyric acid bacteria.
  • any of the following information about the subject may be obtained: - Attribute information of the subject, including any one selected from the group consisting of gender and age; - Test result information on the subject's physical and health condition, including any selected from the group consisting of height, weight, body mass index (BMI), obesity level, body fat, waist circumference, blood pressure, lipids, liver and pancreas function, metabolic system, blood, urine, renal function, and large intestine; Survey results information on the subject's preferences and lifestyle, including any of the following: eating habits (preferences), drinking habits, smoking habits, smoking history, exercise habits, and sleep time; and the subject's subjective symptoms, stress, illnesses currently being treated or monitored, medicines and health foods being taken, medical history, pregnancy and childbirth experience; and the subject's work history and general lifestyle, etc.
  • the information may be obtained based on responses obtained from the subject to predetermined questions (e.g., responses to a questionnaire).
  • the food information providing device is capable of displaying the provided food information on a target terminal.
  • the device further includes a display unit that displays the provided food information.
  • the display unit may be the target terminal, for example, a tablet terminal, a smartphone, or a personal computer.
  • the food information providing device may include an analysis unit that performs analysis of the bacterial flora and fecal substances, the amount of butyric acid, and fecal metabolome analysis of samples obtained from the subject, and may also include an order receiving unit that receives an order for food from the subject based on the provided food information.
  • This embodiment also provides a food information providing method, comprising the steps of: Obtaining information about the gut microbiota of a subject; Deriving information about foods to be provided to the subject based on the information about the intestinal microbiota; and providing the derived food information to the subject.
  • information on the presence or absence or amount of butyric acid bacteria is acquired from information on the intestinal flora
  • information on the food which is a composition containing any one selected from kojibiose and oligosaccharides having kojibiose as a constituent sugar, is derived based on the information on the presence or absence or amount of butyric acid bacteria.
  • Such a method may further include a step of displaying the provided food information on a target terminal.
  • the target terminal may be, for example, a tablet terminal, a smartphone, or a personal computer.
  • This embodiment also provides a method for controlling Faecalibacterium bacteria in the intestine of a subject or a method for supporting the diet or health of a subject, comprising carrying out the above-mentioned method for providing food information and further carrying out the following steps: A method for controlling Faecalibacterium bacteria in the intestines of a subject, or a method for supporting the diet or health of a subject, comprising a step of providing food to the subject based on the derived food information.
  • the food in this embodiment is preferably intended for use as a prebiotic or synbiotic.
  • the food here can also be called a food composition, and the explanation in the composition section above applies as is.
  • a method for culturing butyric acid bacteria preferably bacteria of the genus Faecalibacterium, using any one selected from kojibiose and oligosaccharides having kojibiose as a constituent sugar, or a use of any one selected from kojibiose and oligosaccharides having kojibiose as a constituent sugar in culturing butyric acid bacteria, preferably bacteria of the genus Faecalibacterium.
  • the culturing or use may be performed in an intestinal flora.
  • a method for controlling the proliferation of bacteria of the genus Faecalibacterium in an intestinal flora comprising a step of including any one selected from kojibiose and oligosaccharides having kojibiose as a constituent sugar in an intestinal flora containing bacteria of the genus Faecalibacterium.
  • the step of including can be achieved by adding, providing, strengthening, supplementing, or the like, a target component.
  • Lactobacillus satsumensis JCM12392 was cultured overnight at 30°C in a commercially available MRS liquid medium, and then cooled to below 10°C to terminate the culture.
  • JCM12392 is available from the RIKEN BioResource Center, Microbial Materials Development Division (RIKEN BRC JCM; Tsukuba, Ibaraki, Japan).
  • the resulting culture medium was centrifuged and the supernatant discarded to collect the bacteria, after which an equal volume of citrate phosphate buffer (pH 5.0) was added and the bacteria were collected again to wash the bacteria.
  • the above buffer was added to the obtained bacteria in an amount half that of the original culture medium, and the resulting suspension was used as the enzyme solution.
  • Parabacteroides distasoins JCM5825T and Parabacteroides merdae JCM9497T were cultured in a filtered semi-solid medium for GAM sugar degradation. The culture was then centrifuged and the supernatant was filter-sterilized to remove the bacterial cells.
  • F. prausnitzii NCIMB13872T, F. hattorii, F. longum, F. gallinarum, and F. butyricigenerans, which had been stimulated and cultured in MRC medium, were added at 1% to the filter-sterilized culture medium and cultured under anaerobic conditions for 24 hours. The growth of these Faecalibacterium bacteria was evaluated by measuring the turbidity during the culture.
  • Strains with NCIMB in the strain name are available from the National Collection of Industrial and Marine Bacteria, UK. Strains with JCM in the strain name can be obtained from the RIKEN BioResource Center Microbial Materials Division (RIKEN BRC JCM; Tsukuba, Ibaraki, Japan).
  • Faecalibacterium bacteria by kojibiose and oligosaccharides containing kojibiose may be mediated by the growth of Parabacteroides bacteria.
  • oligosaccharides that have the ability to promote the growth of Parabacteroides bacteria may also have the ability to promote the growth of Faecalibacterium bacteria.
  • Faecalibacterium bacteria are a type of butyric acid bacteria known to produce butyric acid in the intestine. Therefore, it can be said that kojibiose and oligosaccharides containing kojibiose as a constituent sugar can be used to control the proliferation of butyric acid bacteria, control the production of butyric acid in the intestine, and further, to treat diseases or conditions that are improved by controlling the proliferation of butyric acid bacteria.
  • Non-Patent Document 1 It has also been reported that the amount of Faecalibacterium bacteria in the intestines is reduced in patients with inflammatory bowel diseases, including Crohn's disease and ulcerative colitis (Non-Patent Document 1, etc.), and that similar reports have been made in patients with asthma, food allergies, non-alcoholic fatty liver disease, and chronic kidney disease (Non-Patent Documents 2 to 6, respectively).
  • Non-Patent Document 7 Faecalibacterium bacteria in the intestines of patients with irritable bowel syndrome (IBS) (Non-Patent Document 7), inflammatory bowel disease (IBD) (Non-Patent Document 8), Parkinson's disease (Non-Patent Document 9), and cancer (Non-Patent Document 10) is reduced compared to healthy individuals, that administration of this genus of bacteria to IBD model mice improves symptoms such as weight loss and diarrhea (Non-Patent Document 11), and that administration of this genus of bacteria to Alzheimer's disease model mice improves cognitive dysfunction (Non-Patent Document 12).
  • Non-Patent Document 13 It has also been reported that Faecalibacterium prausnitzii has an anti-inflammatory effect in cultured cell lines and TNBS colitis model mice. Therefore, it can be said that kojibiose and oligosaccharides having kojibiose as a constituent sugar can be used to treat these diseases or conditions. Furthermore, it can be said that the ingestion of a composition containing kojibiose and oligosaccharides having kojibiose as a constituent sugar is useful for supporting the dietary habits and promoting the health of a subject.
  • Food Production Example 2 Drinkable Yogurt
  • the raw material cream, skim milk concentrate, and raw material water are mixed and dissolved, heat sterilized at 110°C for 30 seconds, cooled to 43°C, and then a lactic acid bacteria starter consisting of Lactobacillus bulgaricus and Streptococcus thermophilus is added, fermented to an acidity of 0.75, and the homogenized solution is mixed and dissolved with raw material water, pectin, sucralose, a trisaccharide fraction containing galactosyl kojibiose as the main component, and a flavor, heat sterilized at 80°C for 10 minutes, and mixed and stirred under cooling.
  • the mixing ratio of the raw materials is shown in the table below.
  • the resulting drink yogurt can be used for anti-obesity purposes.
  • Raw milk is prepared by mixing 500.0 g of raw milk, 53.2 g of skim milk powder, 23.0 g of fresh cream, 403.6 g of tap water, and 50 g of sucrose.
  • the raw milk is heat-sterilized at a temperature of 95°C, and the heat-sterilized raw milk is cooled.
  • the raw milk is inoculated with 0.5% of Liquorilactobacillus satsumensis concentrate, and fermented under static conditions at 48°C for 18 hours, and Lactobacillus bulgaricus and Streptococcus thermophilus are added as lactic acid bacteria starters.
  • the amount of lactic acid bacteria starter added is 20 g.
  • the raw milk to which the lactic acid bacteria starter has been added is filled into a cup container (capacity: 100 ml, made of plastic).
  • the raw milk filled into the cup container is statically fermented in a fermentation room at a temperature of 43°C until the lactic acid acidity reaches 0.7%.
  • the obtained fermented milk can be used for immune control.
  • the raw milk to which the lactic acid bacteria starter has been added is filled into a cup container (capacity: 100 ml, made of plastic).
  • the raw milk filled into the cup container is left to ferment in a fermentation chamber at a temperature of 43°C until the lactic acid acidity reaches 0.7%.
  • the obtained fermented milk can be used to improve liver function.
  • the present invention supports the maintenance and improvement of people's health by using a composition for controlling the proliferation of butyric acid bacteria, which contains any one selected from the group consisting of kojibiose and oligosaccharides whose constituent sugar is kojibiose.
  • the present invention also provides a food composition and a method for producing food that supports the maintenance and improvement of people's health. Furthermore, the present invention can improve the nutrition of various people, ensure healthy lives, and promote welfare.

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Abstract

L'invention concerne un moyen lutter contre la production d'acide butyrique dans l'intestin. La présente invention aborde le problème de la fourniture d'un moyen de lutter contre la prolifération de bactéries butyriques, dont les bactéries Faecalibacterium sont un exemple représentatif. L'invention concerne une composition pour lutter contre la prolifération de bactéries butyriques, de préférence des bactéries Faecalibacterium, ladite composition contenant un saccharide choisi entre du kojibiose et un oligosaccharide ayant du kojibiose comme que saccharide constitutif. Dans un mode de réalisation, la composition comprend du galactosyl kojibiose comme saccharide choisi entre du kojibiose et un oligosaccharide ayant du kojibiose comme saccharide constitutif.
PCT/JP2024/042331 2023-12-01 2024-11-29 Composition pour lutter contre la prolifération de bactéries butyriques Pending WO2025116013A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0322957A (ja) * 1989-06-20 1991-01-31 Showa Sangyo Co Ltd 食品素材
WO2024043298A1 (fr) * 2022-08-25 2024-02-29 株式会社明治 Composition pour améliorer la flore bactérienne intestinale
WO2024043297A1 (fr) * 2022-08-25 2024-02-29 株式会社明治 Procédé de production de composition, composition contenant un oligosaccharide ainsi obtenue et utilisation dudit procédé et de ladite composition

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0322957A (ja) * 1989-06-20 1991-01-31 Showa Sangyo Co Ltd 食品素材
WO2024043298A1 (fr) * 2022-08-25 2024-02-29 株式会社明治 Composition pour améliorer la flore bactérienne intestinale
WO2024043297A1 (fr) * 2022-08-25 2024-02-29 株式会社明治 Procédé de production de composition, composition contenant un oligosaccharide ainsi obtenue et utilisation dudit procédé et de ladite composition

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DíEZ-MUNICIO MARINA; KOLIDA SOFIA; HERRERO MIGUEL; RASTALL ROBERT A.; MORENO F. JAVIER: "In vitrofaecal fermentation of novel oligosaccharides enzymatically synthesized using microbial transglycosidases acting on sucrose", JOURNAL OF FUNCTIONAL FOODS, ELSEVIER BV, NL, vol. 20, 1 December 2015 (2015-12-01), NL , pages 532 - 544, XP029360158, ISSN: 1756-4646, DOI: 10.1016/j.jff.2015.11.032 *
GARCÍA-CAYUELA TOMÁS, DÍEZ-MUNICIO MARINA, HERRERO MIGUEL, MARTÍNEZ-CUESTA M. CARMEN, PELÁEZ CARMEN, REQUENA TERESA, MORENO F. JAV: "Selective fermentation of potential prebiotic lactose-derived oligosaccharides by probiotic bacteria", INTERNATIONAL DIARY JOURNAL, ELSEVIER APPLIED SCIENCE, BARKING,, GB, vol. 38, no. 1, 1 September 2014 (2014-09-01), GB , pages 11 - 15, XP093142685, ISSN: 0958-6946, DOI: 10.1016/j.idairyj.2014.03.012 *
RUIZ-MATUTE ANA I., BROKL MICHAL, SANZ M. LUZ, SORIA ANA C., CÔTÉ GREG L., COLLINS MICHELLE E., RASTALL ROBERT A.: "Effect of Dextransucrase Cellobiose Acceptor Products on the Growth of Human Gut Bacteria", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 59, no. 8, 27 April 2011 (2011-04-27), US , pages 3693 - 3700, XP093319381, ISSN: 0021-8561, DOI: 10.1021/jf104886d *

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