WO2020251044A1 - Composition ayant pour principe actif une bactérie bifidobacterium - Google Patents

Composition ayant pour principe actif une bactérie bifidobacterium Download PDF

Info

Publication number
WO2020251044A1
WO2020251044A1 PCT/JP2020/023305 JP2020023305W WO2020251044A1 WO 2020251044 A1 WO2020251044 A1 WO 2020251044A1 JP 2020023305 W JP2020023305 W JP 2020023305W WO 2020251044 A1 WO2020251044 A1 WO 2020251044A1
Authority
WO
WIPO (PCT)
Prior art keywords
cells
nite
bifidobacterium
fusobacterium
composition
Prior art date
Application number
PCT/JP2020/023305
Other languages
English (en)
Japanese (ja)
Inventor
真 吉本
俊孝 小田巻
恵梨 密山
Original Assignee
森永乳業株式会社
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 森永乳業株式会社 filed Critical 森永乳業株式会社
Publication of WO2020251044A1 publication Critical patent/WO2020251044A1/fr

Links

Classifications

    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • 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
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a composition for suppressing adsorption of Fusobacterium spp. To mucosal cells.
  • the present invention is selected from the group consisting of ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells containing Bifidobacterium spp.
  • the present invention relates to a pharmaceutical composition and a food or drink composition for the prevention or treatment of a disease or symptom.
  • Bifidobacterium Bifidum G9-1 is known to be effective in the prevention or treatment of 5-fluorouracil-induced enteropathy (Patent Document 1).
  • Bactidobacterium breve and bacteria belonging to Bifidobacterium longum are effective in preventing and improving arthritis (Patent Document 2).
  • Bifidobacterium spp. Are effective in preventing or treating diseases or symptoms such as ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells. Is not known. against this background, there is a demand for ingredients that are effective in preventing or treating diseases or symptoms such as ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells. ..
  • Fusobacterium is a resident bacterium in the human oropharynx and is known to be associated with the onset of periodontal disease (Patent Document 3). Furthermore, in recent years, it has been pointed out that Fusobacterium spp. Are associated with ulcerative colitis, colorectal cancer, esophageal cancer, and preterm birth. It has been reported that a large number of Fusobacterium spp. Inhabit the large intestine of patients with ulcerative colitis and colorectal cancer, and have the ability to adsorb and invade the large intestine mucosal epithelium (Non-Patent Document 1).
  • Non-Patent Document 2 when the presence of Fusobacterium was confirmed in 325 cases of esophageal cancer tissue, the presence of Fusobacterium spp. Was confirmed in 74 cases, and it was reported that the prognosis of esophageal cancer was poor (non-patented). Document 3). In addition, Fap2 contained in Fusobacterium spp.
  • Non-Patent Document 4 has been reported to be a galactose-inhibiting adhesion factor involved in preterm birth. Against this background, the development of a composition for suppressing the adsorption of Fusobacterium spp. To mucosal cells is required.
  • JP-A-2017-0884040 Japanese Unexamined Patent Publication No. 2012-158568 JP-A-2016-192950
  • An object of the present invention is to provide a composition for suppressing adsorption of Fusobacterium spp. To mucosal cells.
  • the present invention also provides for the prevention or treatment of diseases or symptoms selected from the group consisting of ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells. , Pharmaceutical composition and food and drink composition.
  • the present inventors have found that Bifidobacterium bacteria suppress the adsorption of Fusobacterium bacteria to mucosal cells, and Bifidobacterium bacteria cause ulcers caused by inflammation of mucosal cells. We have found that it is effective for the prevention or treatment of diseases or symptoms selected from the group consisting of sexual colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease, and have completed the present invention.
  • the present invention is a composition for suppressing adsorption of Fusobacterium to mucosal cells, which comprises Bifidobacterium as an active ingredient.
  • the composition for suppressing adsorption preferably has the mucosal cells as colonic epithelial cells, esophageal mucosal epithelial cells, uterine vascular endothelial cells, or gum mucosal cells.
  • the bacterium belonging to the genus Bifidobacterium is a bacterium belonging to Bifidobacterium longum subspecies longum, a bacterium belonging to Bifidobacterium bifidam, and a bacterium belonging to Bifidobacterium longum sub. It is preferably one or more bacteria selected from the group consisting of bacteria belonging to Species Infantis.
  • the bacteria belonging to the Bifidobacterium longum subspecies longum are NITE BP-02572, NITE BP-02573 and NITE BP-02574 of the Bifidobacterium longum subspecies longum.
  • the preferred form is one or more bacteria selected from the group consisting of.
  • the adsorption-suppressing composition is one or a plurality of bacteria belonging to the Bifidobacterium Bifidum selected from the group consisting of Bifidobacterium Bifidum NITE BP-1252, NITE BP-02570 and NITE BP-02571.
  • the preferred form is that it is a bacterium.
  • the adsorption-suppressing composition is a group in which the bacteria belonging to the Bifidobacterium longum subspecies infantis consist of Bifidobacterium longum subspecies infantis ATCC 15697 and NITE BP-02623.
  • the preferred form is one or more bacteria selected from.
  • the present invention is selected from the group consisting of ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells containing Bifidobacterium spp.
  • a pharmaceutical composition for the prevention or treatment of a disease or symptom preferably has an inflammation of the mucosal cells in which the Fusobacterium spp. Are involved.
  • the bacterium belonging to the genus Bifidobacterium is a bacterium belonging to Bifidobacterium longum subspecies longum, a bacterium belonging to bifidobacteria bifidam, and a bacterium belonging to bifidobacteria longum subspecies.
  • the preferred form is one or more bacteria selected from the group consisting of bacteria belonging to Infantis.
  • the bacteria belonging to the Bifidobacterium longum subspecies longum consist of Bifidobacterium longum subspecies longum NITE BP-02572, NITE BP-02573 and NITE BP-02574.
  • the preferred form is one or more bacteria selected from the group.
  • one or more bacteria in which the bacterium belonging to the Bifidobacterium Bifidum is selected from the group consisting of Bifidobacterium Bifidum NITE BP-1252, NITE BP-02570 and NITE BP-02571.
  • the pharmaceutical composition is selected from the group in which the bacterium belonging to the Bifidobacterium longum subspecies infantis consists of the Bifidobacterium longum subspecies infantis ATCC 15697 and NITE BP-02623.
  • the preferred form is one or more bacteria.
  • the present invention is selected from the group consisting of ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells containing Bifidobacterium spp.
  • a food or drink composition for the prevention or treatment of a disease or symptom.
  • the food and drink composition preferably has the inflammation of the mucosal cells being the inflammation of the mucosal cells in which Fusobacterium spp. Are involved.
  • the Bifidobacterium bacterium belongs to Bifidobacterium longum subspecies longum, a bacterium belonging to Bifidobacterium bifidam, and a bifidobacteria longum subspecies.
  • the preferred form is one or more bacteria selected from the group consisting of bacteria belonging to Infantis.
  • the bacteria belonging to the Bifidobacterium longum subspecies longum are from Bifidobacterium longum subspecies longum NITE BP-02572, NITE BP-02573 and NITE BP-02574.
  • the preferred form is one or more bacteria selected from the group consisting of.
  • one or more bacteria belonging to the Bifidobacterium Bifidum are selected from the group consisting of Bifidobacterium Bifidum NITE BP-1252, NITE BP-02570 and NITE BP-02571. It is preferably a bacterium.
  • the food and drink composition comprises a group in which the bacterium belonging to the Bifidobacterium longum subspecies infantis consists of Bifidobacterium longum subspecies infantis ATCC 15697 and NITE BP-02623.
  • the preferred form is one or more bacteria of choice.
  • the present invention also provides Bifidobacterium Longum Subspecies Longham NITE BP-02572, NITE BP-02573 and NITE BP-02574, and Bifidobacterium Bifidum NITE BP-02570 and NITE BP-02571. To do.
  • compositions for suppressing adsorption of Fusobacterium spp. To mucosal cells. Further, according to the present invention, the prevention or treatment of a disease or symptom selected from the group consisting of ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells. Pharmaceutical compositions and food and drink compositions for this purpose can be provided.
  • the composition of the present invention contains a bacterium of the genus Bifidobacterium as an active ingredient.
  • the composition of the present invention includes the following aspects 1 and 2.
  • Aspect 1 A composition for suppressing adsorption of Fusobacterium to mucosal cells, which comprises Bifidobacterium as an active ingredient.
  • Aspect 2 Disease selected from the group consisting of ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells containing Bifidobacterium spp. Or a composition for the prevention or treatment of symptoms.
  • Examples of the composition according to the second aspect include pharmaceutical compositions, food and drink compositions, and the like.
  • Bifidobacterium bacterium exerts various physiological functions, and it is reported that the function is due to the growth of the bacterium in the intestine and the substance produced by the bacterium in the intestine (for example, acetic acid). Has been done. Therefore, according to the present invention, it is possible to expect highly safe efficacy of bifidobacteria, which is generally referred to, in a wide range of age groups, and the efficacy is widely used (for foods and drinks, pharmaceuticals). It can be realized for use, feed, etc.).
  • the bifidobacteria of the present invention can be expected to have a probiotic effect, health promotion, dietary habits improvement, intestinal environment improvement, prevention or treatment of intestinal infection, recovery of immunity, or It can also be used for purposes such as improvement.
  • Bifidobacterium spp. are gram-positive obligate anaerobic bacilli.
  • the bacterium belonging to the genus Bifidobacterium is not particularly limited, and for example, a bacterium belonging to Bifidobacterium longum subspecies longum, a bacterium belonging to Bifidobacterium bifidam, and a bacterium belonging to Bifidobacterium longum subspecies. Bacteria belonging to Infantis can be mentioned.
  • Bifidobacterium longum subspecies longum may be simply referred to as Bifidobacterium longum.
  • Bifidobacterium Longum Subspecies Infantis may be simply referred to as Bifidobacterium Infantis.
  • Bifidobacterium longum subspecies longum NITE BP-02572, Bifidobacterium longum subspecies longum NITE BP-02573, Bifidobacterium longum subspecies longum NITE BP-02574, Bifidobacterium Longum Subspecies Longham ATCC BAA-999, Bifidobacterium Bifidum NITE BP-1252, Bifidobacterium Bifidum NITE BP-02570, Bifidobacterium Bifidum NITE BP-02571, Bifidobacterium longum subspecies infantis ATCC 15697, Bifidobacterium longum subspecies infantis NITE BP-02623, and mutant cells thereof can be mentioned.
  • NITE BP-02572, NITE BP-02573, and NITE BP-02574 are all patented microorganisms of the National Institute of Technology and Evaluation (NITE) on November 13, 2017. International deposits have been made to the Deposit Center (Room 122, 2-5-8 Kazusa Kamashita, Kisarazu City, Chiba Prefecture, 292-0818) based on the Budapest Treaty (the deposit numbers are NITE BP-02572, NITE BP-02573, and NITE, respectively). BP-02574.).
  • Bifidobacterium longum subspecies longum ATCC BAA-999 can be obtained from the American Type Culture Collection (Address: 12301 Parklawn Drive, Rockville, Maryland 20852, United States of America).
  • Bifidobacterium Bifidum NITE BP-1252 was launched on February 23, 2012 by the National Institute of Technology and Evaluation (NITE) Patent Microorganisms Depositary Center (2 Kazusakamatari, Kisarazu City, Chiba Prefecture, 292-0818). It has been deposited internationally in (5-8, Room 122) based on the Budapest Treaty (the deposit number is NITE BP-1252).
  • Bifidobacterium Bifidum NITE BP-02570 and NITE BP-02571 are both NITE National Institute of Technology and Evaluation (NITE) Patent Microorganisms Depositary Center ( ⁇ 292-0818, Chiba Prefecture) on November 13, 2017.
  • NITE National Institute of Technology and Evaluation
  • An international deposit has been made based on the Budapest Treaty at 2-5-8, Room 122, Kazusakamatari, Kisarazu City (the deposit numbers are NITE BP-02570 and NITE BP-02571, respectively).
  • Bifidobacterium Longum Subspecies Infantis ATCC 15697 can be obtained from the American Type Culture Collection (Address: 12301 Parklawn Drive, Rockville, Maryland 20852, United States of America).
  • Bifidobacterium Longum Subspecies Infantis NITE BP-02623 was released on January 26, 2018 by the National Institute of Technology and Evaluation (NITE) Patent Microorganisms Depositary Center ( ⁇ 292-0818, Chiba Prefecture).
  • NITE National Institute of Technology and Evaluation
  • An international deposit has been made based on the Budapest Treaty at Room 122, 2-5-8 Kazusakamatari, Kisarazu City (the deposit number is NITE BP-02623).
  • the bacterium is the same bacterium as Bifidobacterium Longum Subspecies Infantis M-63.
  • Bifidobacterium longum subspecies longum NITE BP-02572 is not limited to the above-mentioned bacteria, and may be a bacterium substantially equivalent to the above-mentioned bacteria.
  • Bacteria substantially equivalent to the above-mentioned bacteria are bacteria classified into Bifidobacterium longum subspecies longum, can realize the uses of the above-mentioned aspects 1 and 2, and further, the base sequence of the 16S rRNA gene thereof. However, it has preferably 98% or more, more preferably 99% or more, more preferably 100% homology with respect to the base sequence of the 16S rRNA gene of the above bacterium, and preferably has the same myciology as the above bacterium.
  • the bacteria classified into Bifidobacterium longum subspecies longum also include mutant strains and genetically modified strains having the same bacterium as a parent strain. This also applies to the other cells mentioned above. Further, in the present invention, it is necessary to use one or more kinds of Bifidobacterium spp., And two or more kinds may be used.
  • the nucleotide sequences of the 16S rRNA genes of Bifidobacterium longum subspecies longum NITE BP-02572, NITE BP-02573, and NITE BP-02574 are represented by SEQ ID NOs: 1, 2 and 3, respectively.
  • Each cell was compared with Bifidobacterium longum subspecies longum JCM 1217, which is the most closely related species on the DNA database (BLAST), using a sequence length of 1535 bp, 99.8% and 99.6, respectively. Has homology of% and 99.8%. Therefore, each bacterial cell was judged to be a bacterium classified into Bifidobacterium longum subspecies longum.
  • the nucleotide sequences of the 16S rRNA genes of Bifidobacterium Bifidum NITE BP-02570 and NITE BP-02571 are represented by SEQ ID NOs: 4 and 5, respectively.
  • Each cell has a homology of 99.9% in comparison with Bifidobacterium Bifidum JCM 1255, which is the most closely related species on the DNA database (BLAST), using a sequence length of 1422 bp. Therefore, each bacterial cell was judged to be a bacterium classified into Bifidobacterium Bifidum.
  • Bifidobacterium Longum Subspecies Longham JCM 1217 and Bifidobacterium Bifidum JCM 1255 are from Japan Collection of Microorganisms (Japan Collection of Microorganisms, RIKEN BioResource Center, Japan Collection of Microorganisms, Postal Code: 305-0074) , Address: It can be obtained from 3-1-1 Koyadai, Tsukuba City, Ibaraki Prefecture.
  • the bifidobacteria used in the present invention has an action of suppressing the adsorption of Fusobacterium to mucosal cells. Further, in the second aspect, it is preferable that the bifidobacteria have an action of suppressing the adsorption of Fusobacterium to mucosal cells.
  • the action of suppressing the adsorption of Fusobacterium to mucosal cells means the action of reducing the number of Fusobacterium that adsorbs to mucosal cells in a subject, and the subject ingested Bifidobacterium ("administered"). It means that the number of Fusobacterium spp. Adsorbed to mucosal cells is smaller when it is not ingested (including when it is not administered).
  • Bifidobacterium spp. Can be easily grown by culturing the bacterium.
  • the method for culturing is not particularly limited as long as the bacterium can grow, and a method usually used for culturing a bacterium belonging to the genus Bifidobacterium (Bifidobacterium) can be appropriately modified and used as necessary.
  • the culture temperature may be 25 to 50 ° C, preferably 30 to 40 ° C.
  • the culture is preferably carried out under anaerobic conditions, and for example, the culture can be performed while aerating an anaerobic gas such as carbon dioxide.
  • the cells may be cultured under microaerobic conditions such as liquid static culture.
  • the medium used for culturing is not particularly limited, and a medium usually used for culturing bifidobacteria can be appropriately modified and used as necessary. That is, as the carbon source, for example, saccharides such as galactose, glucose, fructose, mannose, cellobiose, maltose, lactose, sucrose, trehalose, starch, starch hydrolysate, and waste sugar honey can be used depending on the assimilation property.
  • the nitrogen source for example, ammonium salts such as ammonia, ammonium sulfate, ammonium chloride, and ammonium nitrate, and nitrates can be used.
  • inorganic salts for example, sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, ferrous sulfate and the like can be used.
  • organic components such as peptone, soybean flour, defatted soybean meal, meat extract, and yeast extract may be used.
  • MRS medium can be preferably used as the prepared medium.
  • the culture obtained after culturing may be used as it is, diluted or concentrated, or cells recovered from the culture may be used.
  • various additional operations such as heating and freeze-drying can be performed after culturing as long as the effects of the present invention are not impaired.
  • the bacterium belonging to the genus Bifidobacterium may be a live bacterium or a dead bacterium. Examples of the dead bacteria include dead bacteria that have been sterilized by heating or the like.
  • the bacterium of the genus Fusobacterium in the present invention is an anaerobic gram-negative bacillus, which produces a high concentration of butyric acid as a metabolite by intestinal fermentation.
  • the Fusobacterium genus bacterium in the present invention is not particularly limited as long as it adsorbs to mucosal cells, and in the second aspect, those involved in inflammation of mucosal cells are preferable. Involvement in inflammation of mucosal cells includes, for example, adsorption to mucosal cells to cause inflammation of the mucosal cells.
  • a bacterium belonging to Fusobacterium nucleatum a bacterium belonging to Fusobacterium gonidiaformans, a bacterium belonging to Fusobacterium naviforme, and a bacterium belonging to Fusobacterium periodonticum.
  • Bacteria bacteria belonging to Fusobacterium necrophorum, bacteria belonging to Fusobacterium varium, bacteria belonging to Fusobacterium canifelinum, bacteria belonging to Fusobacterium equinum, Fusobacterium gastro Bacteria belonging to Switzerland (Fusobacterium gastrosuis), bacteria belonging to Fusobacterium hwasookii, bacteria belonging to Fusobacterium massiliense, bacteria belonging to Fusobacterium mortiferum, Fusobacterium necrogenes ( Bacteria belonging to Fusobacterium necrogenes, bacteria belonging to Fusobacterium perfoetens, bacteria belonging to Fusobacterium russii, bacteria belonging to Fusobacterium simiae, bacteria belonging to Fusobacterium ulcerans And so on.
  • Both cells can be obtained from the American Type Culture Collection (Address: 12301 Parklawn Drive, Rockville, Maryland 20852, United States of America).
  • Fusobacterium nucleatum subspecies nucleatum ATCC 23726 is not limited to the above-mentioned bacteria, and may be a bacterium substantially equivalent to the above-mentioned bacteria.
  • Bacteria substantially equivalent to the above-mentioned bacteria are bacteria classified into Fusobacterium nucleatum, subspecies, and nucleatum, and are bacteria that can be adsorbed on mucosal cells in the first aspect, and mucous membranes in the second aspect.
  • the base sequence of the 16S rRNA gene is preferably 98% or more, more preferably 99% or more, and more preferably 99% or more of the base sequence of the 16S rRNA gene of the above-mentioned bacterium. It is a bacterium having 100% homology and preferably having the same mycological properties as the above-mentioned bacterium. Involvement in inflammation of mucosal cells includes, for example, adsorption to mucosal cells to cause inflammation of the mucosal cells.
  • the bacteria classified into Fusobacterium nucleatum, subspecies, and nucleatum also include mutant strains and recombinant strains having the same bacterium as a parent strain. This also applies to the other cells mentioned above. Further, in the present invention, it is necessary to use one or more kinds of Fusobacterium spp., And two or more kinds may be used.
  • the mucosal cells in the present invention are untreated, that is, when they are not treated with Bifidobacterium spp., For example, when they are not reacted (coexistence) with Bifidobacterium spp., Fusobacterium spp.
  • the cells are not particularly limited as long as they are adsorbed by bacteria, and are not particularly limited in the above aspect 2, but are preferably cells that cause inflammation by adsorbing Fusobacterium spp.
  • colonic epithelial cells, vascular endothelial cells of the uterus, mucosal epithelial cells of the esophagus, mucosal cells of the gums can be mentioned.
  • the effect of the Bifidobacterium bacterium of the present invention on the adsorption of Fusobacterium bacteria on mucosal cells can be confirmed, for example, by the following method described in Examples. After reacting (coexisting) the colorectal cancer cell line HCT116 with a bacterium belonging to the genus Bifidobacterium, the HCT116 is reacted (coexisting) with FITC (fluorescein isothiocyanate) -labeled Fusobacterium nucleatum ATCC 23726.
  • FITC fluorescein isothiocyanate
  • FITC positive rate when FITC-positive cells are regarded as cells adsorbed by FITC-labeled ATCC 23726, and HCT116 and ATCC 23726 that have not reacted (coexisted) with Bifidobacterium spp. Are reacted (coexisted). Is the control (100%), and it is confirmed by the decrease in the proportion of positive cells (FITC positive rate).
  • composition of the present invention is a concept containing a mixture, and it does not matter whether the components of the composition are uniform or non-uniform.
  • To mucosal cells according to the first aspect of the present invention can be used as a food or drink composition for suppressing adsorption or a pharmaceutical composition for suppressing adsorption.
  • the composition according to the first aspect can be used as a food or drink composition or a pharmaceutical composition for the prevention or treatment of diseases or symptoms involving Fusobacterium spp.
  • the food and drink composition according to the first aspect since the food and drink composition according to the first aspect has an action of suppressing the adsorption of Fusobacterium bacteria to mucosal cells, it is preferably prevented by suppressing the adsorption of Fusobacterium bacteria to mucosal cells.
  • Treatment also includes improvement. Specific examples thereof include prevention or treatment of diseases or symptoms such as ulcerative colitis, colorectal cancer, esophageal cancer, premature birth, and periodontal disease. In this specification, “premature birth” is defined as one of "symptoms”.
  • the composition can be used as a food and drink composition.
  • the inflammation of the mucosal cells is preferably inflammation of the mucosal cells in which the bacterium of the genus Fuzobacterium is involved, and more preferably inflammation of the mucosal cells caused by adsorption of the bacterium of the genus Fuzobacterium to the mucosal cells.
  • the food and drink composition of the present invention contains a bacterium of the genus Bifidobacterium.
  • the food and drink composition may be a food or drink regardless of the form such as liquid, paste, gel-like solid, powder, etc.
  • a bacterium of the genus Bifidobacterium may be a food or drink regardless of the form such as liquid, paste, gel-like solid, powder, etc.
  • liquid food, etc. for example, bread, macaroni, spaghetti, noodles, etc. , Cake mix, fried flour, bread flour and other wheat flour products; instant noodles, cup noodles, retort / cooked foods, canned foods, microwave foods, instant soups / stews, instant miso soups / suckers, canned soups, freeze / dry foods, etc.
  • Instant foods such as instant foods; canned agricultural products, canned fruits, jams and marmalades, pickles, boiled beans, dried agricultural products, processed agricultural products such as cereals (processed grain products); canned marine products, fish hams and sausages, marine products Processed marine products such as paste products, marine delicacies, and boiled Tsukuda; processed livestock products such as canned livestock / pastes, livestock ham / sausage; processed milk, dairy drinks, yogurts, lactic acid bacteria drinks, cheese, ice cream, preparation Milk and dairy products such as powdered milk, cream, and other dairy products; fats and oils such as butter, margarine, and vegetable oil; basic seasonings such as soy sauce, miso, sauces, tomato processing seasonings, mirins, and vinegars; Combined seasonings / foods such as cooking mixes, curry ingredients, sauces, dressings, noodle soups, spices, and other compound seasonings; frozen ingredients, frozen foods, semi-cooked foods, frozen foods, etc.
  • processed agricultural products such as cereal
  • Nutritional beverages such as favorite beverages, baby foods, sprinkles, other commercial foods such as Ochazuke paste; prepared powdered milk for childcare; enteral nutritional foods; special purpose foods, health functional foods (specific health foods, nutritional functional foods, etc.) Foods with functional claims);
  • nutritional supplements include nutritional supplements.
  • the food and drink composition may be a supplement, for example, a tablet-shaped supplement.
  • bifidobacteria can be ingested without being affected by other foods in terms of daily dietary intake and calorie intake.
  • the food and drink composition of the present invention can be produced by adding a bacterium of the genus Bifidobacterium to a raw material of a normal food or drink, and is a normal food or drink except that the bacterium of the genus Bifidobacterium is added. It can be manufactured in the same manner as above.
  • the addition of Bifidobacterium spp. May be carried out at any stage of the manufacturing process of the food or drink composition.
  • the food and drink composition may be produced through the fermentation step by the added Bifidobacterium genus bacterium. Examples of such food and drink compositions include bifidobacteria beverages, fermented milk and the like.
  • the raw material of the food and drink composition the raw material used for ordinary food and drink can be used.
  • the food and drink composition produced can be ingested orally.
  • the food and drink composition of the present invention also includes raw materials for manufacturing the food and drink composition, food additives, and the like, which are added to the food and drink composition during or after the manufacturing process of the food and drink composition.
  • the Bifidobacterium bacterium in the present invention can be used as a starter for fermented milk production.
  • the Bifidobacterium genus bacterium of the present invention can be added later to the produced fermented milk.
  • the food and drink composition of the present invention comprises various proteins such as whey protein, casein protein, soybean protein, or pea protein (pea protein) or mixtures thereof, degradation products; amino acids such as leucine, valine, isoleucine or glutamine; It can be produced by blending components such as vitamins such as vitamin B6 or vitamin C; creatin; citrate; or fish oil with the Bifidobacterium genus bacterium of the present invention.
  • the content of Bifidobacterium spp. in the food or drink composition of the present invention is appropriately set depending on the mode of the food or drink composition, but is usually 1 ⁇ 10 4 to 1 ⁇ 10 13 in the food or drink composition. It is preferably in the range of cfu / g or 1 ⁇ 10 4 to 1 ⁇ 10 13 cfu / ml, 1 ⁇ 10 7 to 1 ⁇ 10 11 cfu / g or 1 ⁇ 10 7 to 1 ⁇ 10 11 cfu / ml. It is more preferable that it is within the range of. “Cfu” represents a colony forming unit. If the Bifidobacterium spp. Is dead, cfu / g or cfu / ml can be replaced with individual cells / g or individual cells / ml.
  • the food and drink composition of the present invention may be ingested alone, or other food and drink compositions or foods and drinks, for example, prevention or treatment of other diseases or symptoms involving Fusobacterium spp.
  • the first aspect It may be ingested together with a food or drink composition for food or food or drink.
  • a disease or symptom selected from the group consisting of ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells. It may be taken together with the food composition of the above or food and drink.
  • the food or drink composition of the present invention can be sold as a food or drink composition or a food or drink whose use for the prevention or treatment of a disease or symptom involving Fusobacterium spp. Is indicated.
  • it can be a food or drink composition or a food or drink with a label such as "for prevention or treatment of a disease or symptom involving Fusobacterium spp.”
  • any wording that expresses the secondary effect of suppressing the adsorption of Fusobacterium spp. To mucosal cells can be used.
  • a disease or symptom selected from the group consisting of ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells It can be sold as a food or drink composition or a food or drink whose use is indicated.
  • indications such as "for prevention or treatment of diseases or symptoms selected from the group consisting of ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells". It can be a food or drink composition or a food or drink.
  • the food / drink composition of the present invention can be provided / sold as a food / drink composition or a food / drink whose use (including health use) such as probiotics is indicated.
  • the "display” means all actions for informing the consumer of the above-mentioned use, and if the display can recall or infer the above-mentioned use, the purpose of the display, the content of the display, and the display. Regardless of the object, medium, etc., all fall under the "indication" of the present invention. However, it is preferable to display it in an expression that allows the consumer to directly recognize the above application. Specifically, the act of describing the above use in the food or drink composition of the present invention or the product or product packaging related to the food or drink, or the transfer, delivery, transfer or transfer of the product or product packaging in which the above use is described.
  • the display it is preferable that the display is permitted by the government or the like (for example, a display obtained based on various systems established by the government and performed in a manner based on such approval).
  • the display is permitted by the government or the like (for example, a display obtained based on various systems established by the government and performed in a manner based on such approval).
  • labeling as health functional foods more specifically health functional foods, functional foods, enteric nutritional foods, special purpose foods, nutritional functional foods, non-medicinal products, etc. can be exemplified. It can exemplify other labeling approved by the Consumer Affairs Agency, for example, foods for specified health use, foods with nutritional function, foods with functional claims, and labeling approved by a similar system.
  • Examples of the latter include labeling as a food for specified health use, labeling as a food for specified health use as a condition, labeling to the effect that it affects the structure and function of the body, disease risk reduction labeling, and functionality based on scientific evidence. Can be illustrated. More specifically, as a food for specified health use specified in the Cabinet Office Ordinance (Cabinet Office Ordinance No. 57, August 31, 2001) regarding permission for special use labeling prescribed in the Health Promotion Law. (In particular, indications for health uses) and similar indications can be exemplified.
  • infant milk for example, infant formula, etc.
  • infant milk is intended to be taken as a substitute for breast milk by infants, preferably 4-12 months old, more preferably 4-6 months old, which alone meets the nutritional requirements of the infant.
  • infant milk is, for example, one or more probiotics of the genus Bifidobacterium; prebiotics such as human milk oligosaccharides, fructooligosaccharides and galactooligosaccharides; derived from casein, soybean, whey or skim milk.
  • Proteins may contain vitamins and minerals essential to daily foods. It can also contain one or more selected from these groups.
  • the pharmaceutical composition of the present invention contains a bacterium of the genus Bifidobacterium.
  • a bacterium belonging to the genus Bifidobacterium may be used as it is, or a physiologically acceptable liquid or solid preparation carrier may be blended and used as a preparation.
  • the dosage form of the pharmaceutical composition of the present invention is not particularly limited, and specifically, tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, syrups, suppositories, injections, etc. Examples thereof include ointments, patches, eye drops, and nasal drops.
  • excipients binders, disintegrants, lubricants, stabilizers, flavoring agents, diluents, surfactants, solvents for injections, etc., which are usually used as formulation carriers. Agents can be used.
  • preparation carrier various organic or inorganic carriers can be used depending on the dosage form.
  • examples of the carrier in the case of a solid preparation include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents and the like.
  • excipients include sugar derivatives such as lactose, sucrose, glucose, mannit, and sorbit; starch derivatives such as corn starch, horse bell starch, ⁇ -starch, dextrin, and carboxymethyl starch; crystalline cellulose, hydroxypropyl cellulose, etc.
  • Cellulose derivatives such as hydroxypropylmethyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose calcium; gum arabic; dextran; purulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminometasilicate; phosphate derivatives such as calcium phosphate; carbonic acid Carbonated carbonate derivatives such as calcium; sulfate derivatives such as calcium sulfate can be mentioned.
  • binder examples include gelatin; polyvinylpyrrolidone; macrogol, etc., in addition to the above-mentioned excipients.
  • disintegrant examples include, in addition to the above-mentioned excipients, chemically modified starch or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and crosslinked polyvinylpyrrolidone.
  • lubricant examples include talc; stearic acid; metal stearate salts such as calcium stearate and magnesium sulfate; colloidal silica; waxes such as pea gum and gay wax; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid.
  • Sodium carboxylic acid salts such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic acid anhydride and silicate hydrate; starch derivatives and the like. Be done.
  • the stabilizer examples include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; acetic acid anhydride; and sorbic acid.
  • Examples of the flavoring and flavoring agent include sweeteners, acidulants, and flavors.
  • Examples of the carrier used in the case of a liquid preparation for oral administration include a solvent such as water, a flavoring and odorant, and the like.
  • the pharmaceutical composition of the present invention is appropriately set depending on the dosage form, usage, age, sex, type of disease, degree of disease, and other conditions, but is usually used. , 1 ⁇ 10 4 to 1 ⁇ 10 13 cfu / g or 1 ⁇ 10 4 to 1 ⁇ 10 13 cfu / ml, preferably 1 ⁇ 10 7 to 1 ⁇ 10 11 cfu / g or 1 ⁇ More preferably, it is in the range of 10 7 to 1 ⁇ 10 11 cfu / ml. If the Bifidobacterium spp. Is dead, cfu / g or cfu / ml can be replaced with individual cells / g or individual cells / ml.
  • the administration time of the pharmaceutical composition of the present invention is not particularly limited, and the administration time can be appropriately selected according to the treatment method for the target disease or symptom. In addition, it may be administered prophylactically or may be used for maintenance therapy. In addition, the administration form is preferably determined according to the formulation form, the age, sex, other conditions of the patient, the degree of the patient's symptoms, and the like. In any case, the pharmaceutical composition of the present invention can be administered once a day or in multiple divided doses, or may be administered once every few days or weeks. Targets include humans, cows, sheep, goats, pigs, dogs, cats, horses and the like.
  • the pharmaceutical composition according to the first aspect has an action of suppressing the adsorption of Fusobacterium bacteria to mucosal cells, it is preferably prevented or treated by suppressing the adsorption of Fusobacterium bacteria to mucosal cells. It can be used for the prevention or treatment of the resulting disease or symptom. "Treatment” also includes improvement. Specific examples thereof include prevention or treatment of diseases or symptoms such as ulcerative colitis, colorectal cancer, esophageal cancer, premature birth, and periodontal disease. In this specification, "premature birth” is defined as one of "symptoms”.
  • the composition can be used as a pharmaceutical composition as described above.
  • the inflammation of the mucosal cells is preferably inflammation of the mucosal cells in which the bacterium of the genus Fuzobacterium is involved, and more preferably inflammation of the mucosal cells caused by adsorption of the bacterium of the genus Fuzobacterium to the mucosal cells.
  • the pharmaceutical composition of the present invention may be administered alone, or for the prevention or treatment of other pharmaceutical compositions or pharmaceuticals, for example, in the above aspect 1, other diseases or symptoms involving Fusobacterium spp.
  • Pharmaceutical composition or drug, pharmaceutical composition or drug for colorectal cancer or esophageal cancer (eg, anticancer drug, etc.), gastrointestinal drug, laxative, analgesic; pharmaceutical composition or drug for ulcerative colitis, periodontal disease It may be used in combination with a pharmaceutical composition or a drug for a disease.
  • Another aspect of the present invention is the use of bifidobacteria in the production of compositions for suppressing the adsorption of Fusobacterium to mucosal cells.
  • another aspect of the present invention is a bifidobacteria bacterium used for suppressing adsorption of Fusobacterium bacterium to mucosal cells.
  • another aspect of the present invention includes a step of administering the Bifidobacterium genus bacterium to the application subject or a step of administering the composition for suppressing the adsorption of the Fusobacterium genus bacterium of the present invention to the mucosal cell to the application subject.
  • Another aspect of the present invention includes a step of administering the Bifidobacterium genus bacterium to the application subject or a step of administering the composition for suppressing the adsorption of the Fusobacterium genus bacterium of the present invention to the application subject.
  • another aspect of the present invention is the prevention or prevention of a disease or symptom selected from the group consisting of ulcerative colitis, colon cancer, esophageal cancer, preterm birth, and periodontal disease caused by inflammation of mucosal cells.
  • Bifidobacterium spp. In the production of therapeutic pharmaceutical or food and drink compositions.
  • another aspect of the present invention is the prevention or prevention of a disease or symptom selected from the group consisting of ulcerative colitis, colon cancer, esophageal cancer, premature birth, and periodontal disease caused by inflammation of mucosal cells. It is a Bifidobacterium spp. Used for treatment.
  • another aspect of the present invention is for inflammation of mucosal cells, which comprises a step of administering a bacterium of the genus Bifidobacterium to an application subject or a step of administering a pharmaceutical composition or a food or drink composition of the present invention to an application subject.
  • a method for preventing or treating a disease or symptom selected from the group consisting of ulcerative colitis, colorectal cancer, esophageal cancer, premature birth, and periodontal disease comprises ulcerative colitis, colorectal cancer, esophageal cancer, premature birth, and periodontal disease caused by mucosal cell inflammation containing Bifidobacterium spp.
  • the display of the function is not particularly limited, but for example, "prevents ulcerative colitis”, “reduces the risk of developing ulcerative colitis”, “reduces the risk of developing ulcerative colitis", “colorectal cancer”. "Preventing”, “Reducing the risk of developing colorectal cancer”, “Reducing the risk of developing colorectal cancer”, “Preventing esophageal cancer”, “Reducing the risk of developing esophageal cancer”, “Esophageal “Reduce the risk of developing colorectal cancer", "Prevent premature birth”, “Reduce the risk of premature birth”, “Prevent periodontal disease”, “Reduce the risk of developing periodontal disease", “Risk of developing periodontal disease””Lower” and so on.
  • the indication of the function may be attached to the composition itself, or may be attached to the container or packaging of the composition.
  • the number of bacteria was calculated from the absorbance at 660 nm of each bacterium culture medium of -02574, and each bacterium of 2.5 ⁇ 10 8 CFU corresponding to MOI 500 was dissolved in 0.1 ml of PBS for 5 ⁇ 10 5 HCT116 cells. .. Then, 5 ⁇ 10 5 HCT116 cells and 2.5 ⁇ 10 8 CFU of each cell were reacted (coexisted) at 37 ° C. for 3 hours in 50 mM phosphate buffer (pH 5.0), and then PBS containing 1% BSA. Washed 3 times with 1 ml.
  • Fusobacterium nucleatum (ATCC 23726) 1 ⁇ 10 10 CFU cultured in GAM medium (GAM bouillon “Nissui”, manufactured by Nissui Pharmaceutical Co., Ltd.) at 37 ° C for 16 hours was FITC using FITC isomer (sigma F7 250). After labeling, washing with PBS was repeated 4 times, and then cells of 2.5 ⁇ 10 7 CFU corresponding to MOI 50 were dissolved in 0.02 ml of PBS.
  • HCT116 cells reacted (coexisted) with each of the above-mentioned cells were reacted (coexisted) with 2.5 ⁇ 10 7 CFU FITC-labeled Fusobacterium nucleatum (ATCC 23726) at room temperature for 1 hour, and then contained 1% BSA. Washing with PBS was repeated 3 times. After that, using a Flowcytometer (BD FACSCanto, manufactured by Becton Dickinson), FITC-positive cells were regarded as cells adsorbed by FITC-labeled Fusobacterium nucleatum (ATCC 23726), and FITC-positive in HCT116 cells treated with each cell. The proportion of cells was calculated. The results are shown in Table 1.
  • the FITC-positive cell rate of HCT116 cells not treated with bacterial cells was 9.89%, whereas that of cells treated with Bifidobacterium breve ATCC 15700 was 8.36%, showing almost no change in the FITC-positive cell rate.
  • the FITC-positive cell rates decreased to 1.19%, 2.04%, and 0.60%, respectively.
  • the number of bacteria was calculated from the absorbance at 660 nm of each bacterial culture medium, and each cell of 1.5 ⁇ 10 8 CFU corresponding to MOI 300 was dissolved in 0.1 ml of PBS for 5 ⁇ 10 5 HCT116 cells. Then, 5 ⁇ 10 5 HCT116 cells and 2.5 ⁇ 10 8 CFU of each cell were reacted (coexisted) at 37 ° C. for 3 hours in 50 mM phosphate buffer (pH 5.0), and then PBS containing 1% BSA. Washed 3 times with 1 ml.
  • Fusobacterium nucleatum (ATCC 23726) 1 ⁇ 10 10 CFU cultured in GAM medium (GAM bouillon “Nissui”, manufactured by Nissui Pharmaceutical Co., Ltd.) at 37 ° C for 16 hours was FITC using FITC isomer (sigma F7 250). After labeling, washing with PBS was repeated 4 times, and then cells of 2.5 ⁇ 10 7 CFU corresponding to MOI 50 were dissolved in 0.02 ml of PBS.
  • HCT116 cells reacted (coexisted) with each of the above-mentioned cells were reacted (coexisted) with 2.5 ⁇ 10 7 CFU FITC-labeled Fusobacterium nucleatum (ATCC 23726) at room temperature for 1 hour, and then contained 1% BSA. Washing with PBS was repeated 3 times. After that, using a Flowcytometer (BD FACSCanto, manufactured by Becton Dickinson), FITC-positive cells were regarded as cells adsorbed by FITC-labeled Fusobacterium nucleatum (ATCC 23726), and FITC-positive in HCT116 cells treated with each cell. The proportion of cells was calculated. The results are shown in Table 2.
  • the FITC-positive cell rate of HCT116 cells not treated with cells was 7.09%, whereas that of cells treated with Bifidobacterium breve ATCC 15700 was 7.67%, showing almost no change in the FITC-positive cell rate.
  • the FITC-positive cell rates decreased to 3.03%, 2.17%, and 2.85%, respectively.
  • the number of bacteria was calculated from the above, and each cell of 2.5 ⁇ 10 7 CFU corresponding to MOI 50 was lysed in 0.1 ml of PBS for 5 ⁇ 10 5 HCT116 cells. Then, 5 ⁇ 10 5 HCT116 cells and 2.5 ⁇ 10 7 CFU of each cell were reacted (coexisted) at 37 ° C. for 2 hours in 50 mM phosphate buffer (pH 5.0), and then PBS containing 1% BSA. Washed 3 times with 1 ml.
  • Fusobacterium nucleatum (ATCC 23726) 1 ⁇ 10 10 CFU cultured in GAM medium (GAM bouillon “Nissui”, manufactured by Nissui Pharmaceutical Co., Ltd.) at 37 ° C for 16 hours was FITC using FITC isomer (sigma F7 250). After labeling, washing with PBS was repeated 4 times, and then cells of 5 ⁇ 10 6 CFU corresponding to MOI 10 were dissolved in 0.02 ml of PBS.
  • HCT116 cells reacted (coexisted) with each of the above-mentioned cells were reacted (coexisted) with 5 ⁇ 10 6 CFU FITC-labeled Fusobacterium nucleatum (ATCC 23726) at room temperature for 1 hour, and then contained 1% BSA. Washing with PBS was repeated 3 times. After that, using a Flowcytometer (BD FACSCanto, manufactured by Becton Dickinson), FITC-positive cells were regarded as cells adsorbed by FITC-labeled Fusobacterium nucleatum (ATCC 23726), and FITC-positive in HCT116 cells treated with each cell. The proportion of cells was calculated. The results are shown in Table 3.
  • the FITC-positive cell rate of HCT116 cells not treated with cells was 7.93%, whereas that of cells treated with Bifidobacterium breve ATCC 15700 was 8.61%, showing almost no change in the FITC-positive cell rate.
  • cells treated with Bifidobacterium longum subsp. Infantis ATCC 15697 had a reduced FITC-positive cell rate of 3.52%.
  • Colorectal cancer cell line HCT116 cells 5 ⁇ 10 5 cells were suspended in 0.1 ml of PBS.
  • Bifidobacterium longum subsp. Infantis ATCC 15697 strain Bifidobacterium longum subsp. Infantis NITE BP-02623 (M-63) cultured in GAM medium (GAM bouillon “Nissui", manufactured by Nissui Pharmaceutical Co., Ltd.) at 37 ° C for 16 hours, respectively.
  • the number of bacteria was calculated from the absorbance at 660 nm of each bacterial culture medium of the strain, and each cell of 5 ⁇ 10 7 CFU corresponding to MOI 100 was dissolved in 0.1 ml of PBS for 5 ⁇ 10 5 HCT116 cells.
  • FITC-positive cells were regarded as cells adsorbed by FITC-labeled Fusobacterium nucleatum (ATCC 23726 strain), and FITC in HCT116 cells treated with each cell. The percentage of positive cells was calculated. The results are shown in Table 4. As shown in the results below, the FITC-positive cell rate of HCT116 cells not treated with bacterial cells was 27.6%, whereas that of cells treated with the Bifidobacterium longum subsp. Infantis ATCC 15697 strain was 5.2%, Bifidobacterium longum subsp. In cells treated with infantis NITE BP-02623 (M-63) strain, the FITC positive cell rate decreased to 2.3%.
  • Each bacterial powder and Whey protein concentrate (WPC) are uniformly mixed to obtain a composition.
  • the crystalline cellulose is put into a stirring granulator and mixed. Then, purified water is added to granulate and the granulated product is dried to obtain a granulated product containing an extract component of each bacterium and containing an excipient.
  • Oral administration of the composition can be expected to have an effect of suppressing adsorption of bacteria of the genus Fuzobacterium to colonic epithelial cells, vascular endothelial cells of the uterus, mucosal epithelial cells of the esophagus, and mucosal cells of the gums.
  • CFU / kg body weight / day Is 1 ⁇ 10 8 to 1 ⁇ 10 10 CFU / kg body weight / day and is provided daily for one week at breakfast. If the bifidobacteria are dead, CFU / kg bw / day can be replaced with individual cells / kg bw / day. It may be mixed with food and drink such as fermented milk.
  • oligosaccharide isomaltooligosaccharide, lactulose, raffinose, fructooligosaccharide, galactooligosaccharide, soybean oligosaccharide, and human milk oligosaccharide (HMO) can be used.
  • sialic acid 2'-fucosyl lactose, 3-fucosyl lactose, 2', 3-difucosyl lactose, 3'-sialyl lactose, 6'-sialyl lactose, 3-fucosyl-3'-sialyl Lactose, lacto-N-tetraose, lacto-N-neotetraose, lacto-N-fucopentaose I, lacto-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V, lacto-N-difucosyl Hexaose I, lacto-N-difucosyl hexaose II, and lactose-N-sialyl pentaose, LSTa, LSTb, LSTc and the like can
  • Oral administration of the composition can be expected to have an effect of suppressing adsorption of bacteria of the genus Fuzobacterium to colonic epithelial cells, vascular endothelial cells of the uterus, mucosal epithelial cells of the esophagus, and mucosal cells of the gums.
  • a composition can be obtained in the same manner as in Production Example 4 except that at least one or two kinds are used from Bifidobacterium bifidum NITE BP-1252, NITE BP-02570, and NITE BP-02571.
  • a composition can be obtained in the same manner as in Production Example 4 except that at least one or two kinds are used from Bifidobacterium longum subsp. Infantis ATCC 15697 and NITE BP-02623.
  • a lactic acid bacterium starter is added (inoculated) to a heat-sterilized sterilized emulsion and fermented at a predetermined fermentation temperature to obtain a fermented product. Fermentation forms curds.
  • the lactic acid bacterium starter for example, lactic acid bacteria usually used for yogurt production such as Lactobacillus bulgaricus, Lactococcus lactis, and Streptococcus thermophilus can be used.
  • the pH reaches the target value, the formed curd is crushed by stirring and cooled to 10 ° C. or lower to obtain a fermented product. By cooling to 10 ° C. or lower, the activity of lactic acid bacteria can be reduced and the production of acid can be suppressed.
  • the fermented product obtained in the fermentation step is heat-treated to obtain a fermented product after heating (fermented product after heat treatment).
  • a fermented product after heating By appropriately heating the fermented product, it is possible to suppress the production of acid by lactic acid bacteria in the fermented product after heating. As a result, it is possible to suppress a decrease in pH during the subsequent production process and / or during storage of the concentrated fermented milk containing bifidobacteria, and as a result, the survivability of bifidobacteria can be improved.
  • the Bifidobacterium genus bacterium of the present invention is added to the fermented product after heating obtained in the heat treatment step.
  • the amount of Bifidobacterium to be added is preferably 1 ⁇ 10 7 to 1 ⁇ 10 11 CFU / ml, more preferably 1 ⁇ 10 8 to 1 ⁇ 10 10 CFU / ml, based on the fermented product after heating. If the bifidobacteria are dead, CFU / ml can be replaced with individual cells / ml. After heating, Bifidobacterium spp. Are added to the fermented product and then concentrated. The concentration step can be carried out by appropriately using a known concentration method. For example, a centrifugation method or a membrane separation method can be used.
  • whey in the concentrate (fermented product after heating to which bifidobacteria are added) is removed to obtain concentrated fermented milk containing bifidobacteria having an increased solid content concentration.
  • concentrated fermented milk containing bifidobacteria having an increased solid content concentration.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Molecular Biology (AREA)

Abstract

L'invention a pour objet de fournir une composition pour inhibition d'adsorption d'une bactérie Fusobacterium dans les cellules des muqueuses, et de fournir une composition alimentaire ainsi qu'une composition de boisson ou d'aliment qui sont destinées à la prévention ou au traitement de maladies ou de symptômes parmi une colite ulcéreuse, un cancer du gros intestin, un cancer de l'œsophage, une naissance prématurée et une maladie parodontale, provoqués par une inflammation des cellules des muqueuses. À cet effet, l'invention concerne une composition pour inhibition d'adsorption d'une bactérie Fusobacterium dans les cellules des muqueuses, ayant pour principe actif une bactérie Bifidobacterium, et une composition alimentaire ainsi qu'une composition de boisson ou d'aliment ayant également pour principe actif une bactérie Bifidobacterium, qui sont destinées à la prévention ou au traitement de maladies ou de symptômes parmi une colite ulcéreuse, un cancer du gros intestin, un cancer de l'œsophage, une naissance prématurée et une maladie parodontale, provoqués par une inflammation des cellules des muqueuses.
PCT/JP2020/023305 2019-06-13 2020-06-12 Composition ayant pour principe actif une bactérie bifidobacterium WO2020251044A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201962860948P 2019-06-13 2019-06-13
US62/860,948 2019-06-13

Publications (1)

Publication Number Publication Date
WO2020251044A1 true WO2020251044A1 (fr) 2020-12-17

Family

ID=73781236

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2020/023305 WO2020251044A1 (fr) 2019-06-13 2020-06-12 Composition ayant pour principe actif une bactérie bifidobacterium

Country Status (1)

Country Link
WO (1) WO2020251044A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117210380A (zh) * 2023-11-09 2023-12-12 天赋能(天津)功能食品研究发展有限公司 长双歧杆菌婴儿亚种nku fb3-14在抑制肿瘤方面的应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016166169A (ja) * 2015-03-06 2016-09-15 株式会社ファンケル ダイエット用の製剤
WO2018155565A1 (fr) * 2017-02-24 2018-08-30 森永乳業株式会社 Composition pour soulager des troubles de la santé mentale
WO2018180728A1 (fr) * 2017-03-30 2018-10-04 森永乳業株式会社 Composition favorisant l'expression d'un gène anti-inflammatoire
WO2019117212A1 (fr) * 2017-12-12 2019-06-20 森永乳業株式会社 Composition contenant une bactérie appartenant au genre bifidobacterium en tant que substance active

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016166169A (ja) * 2015-03-06 2016-09-15 株式会社ファンケル ダイエット用の製剤
WO2018155565A1 (fr) * 2017-02-24 2018-08-30 森永乳業株式会社 Composition pour soulager des troubles de la santé mentale
WO2018180728A1 (fr) * 2017-03-30 2018-10-04 森永乳業株式会社 Composition favorisant l'expression d'un gène anti-inflammatoire
WO2019117212A1 (fr) * 2017-12-12 2019-06-20 森永乳業株式会社 Composition contenant une bactérie appartenant au genre bifidobacterium en tant que substance active

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
NAGANUMA MAKOTO ET AL.: "Treatment of inflammatory digestive system disease and prevention of carcinogenesis (inflammatory bowel disease) practise of long term drug treatmentof inflammatory bowel disease from the viewpoint of carcinogenesis prevention.", CLINICS IN GASTROENTEROLOGY, vol. 13, no. 6, 2010, pages 675 - 680, ISSN: 1344-3070 *
VANDER HAAR EMILIE L., SO JEEWON, GYAMFI-BANNERMAN CYNTHIA, HAN YIPING W.: "Fusobacterium nucleatum and adverse pregnancy outcomes: Epidemiological and mechanistic evidence", ANAEROBE, vol. 50, April 2018 (2018-04-01), pages 55 - 59, XP055770964 *
YAMAMURA, K. ET AL.: "Human Microbiome Fusobacterium Nucleatum in Esophageal Cancer Tissue Is Associated with Prognosis", CLINICAL CANCER RESEARCH, vol. 22, no. 22, 2016, pages 5574 - 5581, XP055636821, DOI: 10.1158/1078-0432.CCR-16-1786 *
YOSHIMURA ATSUTOSHI ET AL.: "Induction of TNT- a release frommouse peritoneal macrophages by stimulation with LPS from periodontopathic bacteria", JOURNAL OF THE JAPANESE SOCIETY OF PERIODONTOLOGY, vol. 37, no. 3, 1995, pages 468 - 474 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117210380A (zh) * 2023-11-09 2023-12-12 天赋能(天津)功能食品研究发展有限公司 长双歧杆菌婴儿亚种nku fb3-14在抑制肿瘤方面的应用
CN117210380B (zh) * 2023-11-09 2024-01-26 天赋能(天津)功能食品研究发展有限公司 长双歧杆菌婴儿亚种nku fb3-14在抑制肿瘤方面的应用

Similar Documents

Publication Publication Date Title
JPWO2019117212A1 (ja) ビフィドバクテリウム属細菌を有効成分とする組成物
WO2020246585A1 (fr) Composition nutritionnelle
WO2021149663A1 (fr) Composition
WO2020246583A1 (fr) Composition
JP2019116423A (ja) 整腸用組成物
JP7436358B2 (ja) 母乳成分増強用組成物
WO2020251044A1 (fr) Composition ayant pour principe actif une bactérie bifidobacterium
WO2019188943A1 (fr) Composition pour prévenir et/ou améliorer une diminution du débit sanguin cérébral
JP7368484B2 (ja) 組成物並びに該組成物含有する飲食品組成物および調製乳
WO2020116511A1 (fr) Composition servant à la suppression d'une infection au norovirus
JP6847577B2 (ja) ビフィドバクテリウム属細菌および／または乳酸菌の増殖促進および／または減少抑制剤
WO2021025154A1 (fr) Composition pour bébés et nourrissons destinée à améliorer la capacité de mémoire dans l'enfance
JP7152472B2 (ja) Ｆｇｆ２１分泌促進用組成物
JP7266580B2 (ja) 学童期以降の高血糖に起因する疾患の予防のための乳幼児用組成物
JP2021023188A (ja) ラクチュロースを資化しないビフィドバクテリウム属細菌の増殖促進用組成物
JP6978621B1 (ja) 組成物
JP7333732B2 (ja) 筋肉量及び／又は筋力の維持、或いは筋肉量及び／又は筋力の低下抑制用組成物、並びに、該組成物を用いた医薬品組成物及び飲食品組成物
JP2022016960A (ja) 健康寿命延長用組成物

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: 20823311

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20823311

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP