Fermented milk for increasing IgA crossing pathogenic bacteria of periodontal disease in human saliva, food composition containing said fermented milk as active ingredient, fermented milk for maintaining or improving oral health, and food composition containing fermented milk for maintaining or improving oral health as active ingredient

Abstract

The present invention addresses the problem of providing a more easily and highly safe preventive or inhibitory measure against an increase in periodontal disease pathogenic bacteria. The fermented milk according to the present invention contains lactic acid bacteria belonging to the genus Lactobacillus and has a function of increasing IgA crossing pathogenic bacteria of periodontal diseases in human saliva. It is required to be illustrated that the lactic acid bacteria of the genus Lactobacillus are preferably lactic acid bacteria of the genus Lactobacillus capable of producing exopolysaccharides, more preferably Lactobacillus delbrueckii, further preferably Lactobacillus delbrueckii subsp. Bulgaricus, and particularly preferably Lactobacillus delbrueckii subsp. Bulgaricus OLL1073R-1 (accession number: FERM BP-10741) lactic acid bacteria.

Description

Technical Field

[0001] The present invention relates to a fermented milk that increases IgA cross-reactive with periodontal disease pathogens in human saliva and a food composition containing the fermented milk as an active ingredient. In addition, the present invention relates to a fermented milk for maintaining or improving oral health and a food composition containing the fermented milk as an active ingredient. Background Art

[0002] In recent years, various studies on oral diseases have been conducted. Among oral diseases, in particular, studies on periodontal disease have received much attention (for example, refer to Patent Document 1). Periodontal disease is a general term for inflammatory diseases occurring in periodontal tissues caused by periodontal disease pathogens such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, which are classified as the Red complex (the most important periodontal disease pathogens), and Fusobacterium nucleatum (refer to Non-Patent Document 1). As periodontal disease progresses, the inflammation of periodontal tissues becomes chronic, and eventually tooth loss occurs due to the resorption of alveolar bone.

[0003] In addition, studies have shown that the above-mentioned periodontal disease pathogens not only cause periodontal disease but also other major diseases. For example, studies have shown that Porphyromonas gingivalis produces potent proteolytic enzymes (proteases) such as gingipain, and is thus also closely related to systemic diseases such as atherosclerosis (refer to Non-Patent Document 2). In addition, studies have shown that Fusobacterium nucleatum is closely related to the occurrence of cancer, especially the onset and progression of colorectal cancer (refer to Non-Patent Documents 3 and 4). Furthermore, it has been found that saliva containing these periodontal disease pathogens reaches the lungs through the trachea, and thus the periodontal disease pathogens in the saliva infect the lungs, causing aspiration pneumonia. In summary, preventing or suppressing the increase of these periodontal disease pathogens and maintaining or improving oral health can not only prevent periodontal disease but also contribute to the prevention of major diseases such as systemic diseases, aspiration pneumonia, and cancer, and thus also contribute to improving the quality of life (QOL).

[0004] Conventionally, in order to prevent or suppress the increase of periodontal disease pathogens, methods such as directly killing periodontal disease pathogens with a mouthwash containing a bactericide or an antibacterial agent and a drug administration method by taking an antibiotic have been used. However, especially for infants and the elderly, from the viewpoints of accidental ingestion and side effects, these methods accompanied by bactericides, antibacterial agents, or antibiotics are sometimes not considered highly safe methods. Therefore, in addition to these methods, a more relaxed and highly safe preventive or inhibitory measure against the increase of periodontal disease pathogens is needed.

[0005] Prior art documents

[0006] Patent documents

[0007] Patent Document 1: Japanese Patent Application Laid-Open No. 2022-158418

[0008] Non-patent documents

[0009] Non-patent Document 1: Journal of Clinical Periodontology, Dec 2005, Vol. 25, Issue. 2, p. 134-144

[0010] Non-patent Document 2: Folia Pharmacol. Jpn. 122, 37 - 44 (2003)

[0011] Non-patent Document 3: Anaerobe, June 2016, vol. 39, p. 1 - 3

[0012] Non-patent Document 4: A prospective interventional trial on the effect of periodontal treatment on Fusobacterium nucleatum abundance in patients with colorectal tumours Summary of the invention

[0013] Problems to be solved by the invention

[0014] The technical problem of the present invention is to provide a more relaxed and highly safe preventive or inhibitory measure against the increase of periodontal disease pathogenic bacteria.

[0015] Solutions for solving the problems

[0016] In order to solve the above technical problems, the inventors of the present invention focused on fermented milk containing lactic acid bacteria of the genus Lactobacillus, and studied the effect of ingesting this fermented milk on the production amount of IgA cross-reacting with periodontal disease pathogenic bacteria in human saliva. And, as a result, it was found that by having a person ingest this fermented milk, the IgA cross-reacting with periodontal disease pathogenic bacteria in the saliva of this person can be increased, thereby completing the present invention.

[0017] That is, the present invention is as follows.

[0018] (1) A fermented milk for increasing IgA cross-reacting with periodontal disease pathogenic bacteria in human saliva, which contains lactic acid bacteria of the genus Lactobacillus.

[0019] (2) The fermented milk according to (1), wherein the lactic acid bacterium of the genus Lactobacillus is a lactic acid bacterium of the genus Lactobacillus capable of producing exopolysaccharide.

[0020] (3) The fermented milk according to (2), which is obtained by fermenting milk raw materials with a lactic acid bacterium of the genus Lactobacillus capable of producing exopolysaccharide.

[0021] (4) The fermented milk according to any one of (1) to (3), wherein the lactic acid bacterium of the genus Lactobacillus is Lactobacillus delbrueckii subsp. bulgaricus.

[0022] (5) The fermented milk according to (4), wherein Lactobacillus delbrueckii subsp. bulgaricus is Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (FERM BP-10741).

[0023] (6) The fermented milk according to any one of (1) to (5), which further contains Streptococcus thermophilus.

[0024] (7) The fermented milk according to any one of (1) to (6), wherein the periodontal disease pathogen is Porphyromonas gingivalis.

[0025] (8) The fermented milk according to any one of (1) to (6), wherein the periodontal disease pathogen is Fusobacterium nucleatum.

[0026] (9) The fermented milk according to any one of (1) to (8), wherein the person is an elderly person.

[0027] (10) The fermented milk according to (9), wherein the elderly person is a person aged 65 or above.

[0028] (11) A fermented milk for maintaining or improving oral health, which contains a lactic acid bacterium of the genus Lactobacillus.

[0029] (12) The fermented milk according to (11), wherein maintaining or improving oral health is to inhibit the increase in the number of periodontal disease pathogens or reduce the number of periodontal disease pathogens.

[0030] (13) The fermented milk according to (12), wherein the number of periodontal disease pathogens is the number of Porphyromonas gingivalis.

[0031] (14) The fermented milk according to (12), wherein the number of periodontal disease pathogens is the number of Fusobacterium nucleatum.

[0032] (15) A fermented milk for reducing the risk of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis, which contains lactic acid bacteria of the genus Lactobacillus.

[0033] (16) A fermented milk for preventing the exacerbation of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis, which contains lactic acid bacteria of the genus Lactobacillus.

[0034] (17) The fermented milk according to (15) or (16), which is achieved by increasing IgA cross-reacting with periodontal disease pathogens.

[0035] (18) A food composition for increasing IgA cross-reacting with periodontal disease pathogens in human saliva, which uses the fermented milk described in any one of (1) to (10) as an active ingredient.

[0036] (19) A food composition for maintaining or improving oral health, which uses the fermented milk described in any one of (11) to (14) as an active ingredient.

[0037] (20) A food composition for reducing the risk of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis, which uses the fermented milk described in (15) as an active ingredient.

[0038] (21) A food composition for preventing the exacerbation of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis, which uses the fermented milk described in (16) as an active ingredient.

[0039] In addition, the present invention also includes the following inventions.

[0040] (22) A method for increasing IgA cross-reacting with periodontal disease pathogens in the saliva of an object, which administers a fermented milk containing lactic acid bacteria of the genus Lactobacillus to an object in need.

[0041] (23) Use of fermented milk containing lactic acid bacteria of the genus Lactobacillus for increasing IgA cross-reactive with periodontal disease pathogens in human saliva.

[0042] (24) A fermented milk containing lactic acid bacteria of the genus Lactobacillus, which is used as a composition for increasing IgA cross-reactive with periodontal disease pathogens in human saliva.

[0043] (25) Use of lactic acid bacteria of the genus Lactobacillus for manufacturing fermented milk for increasing IgA cross-reactive with periodontal disease pathogens in human saliva.

[0044] (26) A method for maintaining or improving oral health of a subject, which comprises administering to a subject in need thereof a fermented milk containing lactic acid bacteria of the genus Lactobacillus.

[0045] (27) Use of fermented milk containing lactic acid bacteria of the genus Lactobacillus for maintaining or improving oral health.

[0046] (28) A fermented milk containing lactic acid bacteria of the genus Lactobacillus, which is used as a composition for maintaining or improving oral health.

[0047] (29) Use of lactic acid bacteria of the genus Lactobacillus for manufacturing fermented milk for maintaining or improving oral health.

[0048] (30) A method for reducing the risk of developing rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis, which comprises administering to a subject in need thereof a fermented milk containing lactic acid bacteria of the genus Lactobacillus.

[0049] (31) Use of fermented milk containing lactic acid bacteria of the genus Lactobacillus for reducing the risk of developing rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis.

[0050] (32) A fermented milk containing lactic acid bacteria of the genus Lactobacillus, which is used as a composition for reducing the risk of developing rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis.

[0051] (33) Use of lactic acid bacteria of the genus Lactobacillus for producing fermented milk for reducing the risk of developing rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature birth / low birth weight, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis.

[0052] (34) A method for preventing the exacerbation of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature birth / low birth weight, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis, which comprises administering fermented milk containing lactic acid bacteria of the genus Lactobacillus to a subject in need thereof.

[0053] (35) Use of fermented milk containing lactic acid bacteria of the genus Lactobacillus for preventing the exacerbation of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature birth / low birth weight, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis.

[0054] (36) A fermented milk containing lactic acid bacteria of the genus Lactobacillus, which is used as a composition for preventing the exacerbation of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature birth / low birth weight, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis.

[0055] (37) Use of lactic acid bacteria of the genus Lactobacillus for producing fermented milk for preventing the exacerbation of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature birth / low birth weight, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis.

[0056] Effects of the Invention

[0057] According to the present invention, it is possible to prevent or inhibit the increase of periodontal disease pathogens more safely and easily than conventional methods. In addition, by ingesting the fermented milk of the present invention, it is possible to increase IgA in the saliva of the person that cross-reacts with periodontal disease pathogens. Furthermore, the fermented milk of the present invention can maintain or improve oral health. Therefore, by ingesting the fermented milk of the present invention, it is possible to prevent periodontal disease and prevent major diseases more safely and easily than conventional methods. Brief Description of the Drawings

[0058] Figure 1 It is a graph showing the effect of Meiji Probio yogurt R-1 in the hard type of the test example on the secretion rate of IgA in saliva cross-reacting with Porphyromonas gingivalis and Fusobacterium nucleatum, which are periodontal disease pathogenic bacteria, in the residents of Special Nursing Home A for the Elderly and Nursing Care Facility for the Elderly B.

[0059] Figure 2 It is a graph showing the correlation between the IgA secretion rate cross-reacting with Fusobacterium nucleatum (Fn) and the presence ratio of Fusobacterium nucleatum in the tongue coating. Detailed Description of the Invention

[0060] The fermented milk of the embodiment of the present invention is fermented milk containing lactic acid bacteria of the genus Lactobacillus or fermented milk prepared using lactic acid bacteria of the genus Lactobacillus, and has the function of increasing IgA in human saliva cross-reacting with periodontal disease pathogenic bacteria. In addition, the fermented milk of the embodiment of the present invention can maintain or improve oral health. In addition, the fermented milk of the embodiment of the present invention can prevent or inhibit systemic diseases caused by periodontal disease pathogenic bacteria and can prevent or inhibit the exacerbation of systemic diseases that can be exacerbated by periodontal disease pathogenic bacteria by preventing or inhibiting the increase of periodontal disease pathogenic bacteria. It should be noted that this fermented milk is particularly effective in increasing IgA in human saliva cross-reacting with periodontal disease pathogenic bacteria. Hereinafter, the definitions of each expression of the present invention will be described in detail.

[0061] 1. Lactic acid bacteria of the genus Lactobacillus

[0062] The sequence number 1 shown in the following sequence listing shows the base sequence (sometimes also referred to as "nucleotide sequence") of the V1-V3 region of the 16S rRNA gene of Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (corresponding to the base sequence at positions 34-535 in the full-length sequence of the 16S rRNA gene). The lactic acid bacteria of the genus Lactobacillus in the embodiments of the present invention are the general name of all bacteria taxonomically recognized as bacteria of the genus Lactobacillus, and are not limited by species, strains, etc. It should be noted that the lactic acid bacteria of the genus Lactobacillus are sometimes classified into either plant-derived or animal-derived according to their sources, but in the present invention, both plant-derived lactic acid bacteria and animal-derived lactic acid bacteria can be used. The strain of the lactic acid bacteria of the genus Lactobacillus in the present invention is preferably one or more strains of the lactic acid bacteria of the genus Lactobacillus that can produce fermented milk (such as yogurt, etc.) with sufficient eating experience. As such lactic acid bacteria of the genus Lactobacillus, lactic acid bacteria of the genus Lactobacillus having a 16S rRNA gene with a sequence identity of 95% or more with the base sequence of this sequence number 1 (that is, the whole or a characteristic part of the sequence of the 16S rRNA gene (V1 region, V2 region, V3 region, or the whole or a part of the V1 region and V2 region and V3 region, or a part including the V1 region and V2 region and V3 region, etc.)) are preferred, more preferably lactic acid bacteria of the genus Lactobacillus having a 16S rRNA gene with a sequence identity of 98% or more with the base sequence of this sequence number 1, further preferably lactic acid bacteria of the genus Lactobacillus having a 16S rRNA gene with a sequence identity of 99% or more with the base sequence of this sequence number 1, and particularly preferably lactic acid bacteria of the genus Lactobacillus having a 16S rRNA gene with a sequence identity of 99.5% or more with the base sequence of this sequence number 1.

[0063] (Sequence Listing)

[0064] <16S rRNA gene (Sequence number 1)>

[0065]

[0066] In the embodiments of the present invention, when sequence identity is mentioned, unless otherwise specified, it refers to the ratio of the number of identical bases shared between two sequences when the two sequences are aligned in an optimal manner. Analysis of base sequence identity can be performed using algorithms or programs well-known to those skilled in the art (e.g., BLASTN, BLASTP, BLASTX, ClustalW). Regarding the parameters when using the programs, those skilled in the art can appropriately set them, and the default parameters of each program can also be used. The specific methods of these analysis methods are also well-known to those skilled in the art. In the calculation of identity, commercially available gene information processing software can also be used.

[0067] In addition, strains having the same mycological properties as Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (hereinafter sometimes referred to as "this strain") can also be used. (For example, including derivative strains and breeding strains). Its mycological properties are as follows.

[0068] (1) Morphological characteristics

[0069] Cell shape: bacillus

[0070] Motility: none

[0071] Presence or absence of spores: none

[0072] Gram staining property: positive

[0073] (2) Growth state on medium

[0074] This strain was spread on a plate of BL agar medium (Glory Science Co., Ltd.) and cultured at 37 °C for 48 hours by the steel wool method, showing an opaque and rough colony morphology.

[0075] (3) Physiological characteristics

[0076] Reduction of nitrate: negative

[0077] Indole production: negative

[0078] Gelatin liquefaction: negative

[0079] Catalase: negative

[0080] Attitude towards oxygen: facultative anaerobiosis

[0081] D(-)-lactic acid is produced by homofermentation of glucose without gas production. Growth at 10 °C in BL liquid medium is negative, and growth at 45 °C is positive.

[0082] Arginine decomposability: negative

[0083] Gas production from malic acid: Negative

[0084] Decomposability of various carbohydrates (Positive +, Negative -)

[0085]

[0086]

[0087] (4) Polysaccharide productivity

[0088] This strain has the following characteristics: It has polysaccharide productivity and produces extracellularly a polysaccharide containing phosphorus with galactose and glucose as constituent sugars.

[0089] The Lactobacillus lactic acid bacteria as an embodiment of the present invention include, for example, Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus johnsonii, Lactobacillus kefiranofaciens, and Lactobacillus paragasseri. After the reclassification of lactic acid bacteria published in the paper "A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae" in INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, Volume 70, Issue 4, released on April 15, 2020, these 8 strains are still classified as the genus Lactobacillus. Therefore, it can be speculated that they will show similar properties and can achieve the target effect. In addition, among the above strains, Lactobacillus lactic acid bacteria that can produce exopolysaccharides are also preferred. Among the above strains, Lactobacillus delbrueckii is more preferred, Lactobacillus delbrueckii subsp. bulgaricus is further preferred, and Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (deposit number: FERM BP-10741) lactic acid bacteria (i.e., OLL1073R-1 strain) is particularly preferred.

[0090] In addition, the exopolysaccharide mentioned here is not particularly limited as long as it has the target effect, but preferably the exopolysaccharide produced by fermenting raw milk with the above-mentioned lactic acid bacteria. The exopolysaccharide used in the embodiments of the present invention can be one kind or a combination of two or more kinds. In addition, the exopolysaccharide preferably contains phosphorylated polysaccharide. In addition, the exopolysaccharide may also contain non-phosphorylated polysaccharide, but it is preferred that the non-phosphorylated polysaccharide does not contain sulfated polysaccharide.

[0091] In addition, as Lactobacillus lactic acid bacteria that produce extracellular polysaccharides containing galactose and glucose as constituent sugars, in addition to the OLL1073R-1 strain, for example, the following Lactobacillus lactic acid bacteria have also been reported. It is considered that these Lactobacillus lactic acid bacteria can achieve the target effect.

[0092] · Lactobacillus johnsonii 151 strain (Non-patent literature: Gorska-Froczek, S., Sandstrom, C., Kenne, L., Paociak, M., Brzozowska, E., Strus, M., Heczko, P., Gamian, A., 2013. The structure and immunoreactivity of exopolysaccharide isolated from Lactobacillus johnsonii strain 151. Carbohydr Res. 378, 148-153.)

[0093] · Lactobacillus delbrueckii subsp. bulgaricus NCFB2074 (Non-patent literature: Harding, L.P., Marshall, V.M., Hernandez, Y., Gu, Y., Maqsood, M., Mclay, N., Laws, A.P., 2005. Structural characterisation of a highly branched exopolysaccharide produced by Lactobacillus delbrueckii ssp. bulgaricus NCFB2074. Carbohydr Res. 340, 1107-1111.)

[0094] · Lactobacillus fermentum TDS030603 (Non-patent literature: K. Fukuda, T. Shi, K. Nagami, F. Leo, T. Nakamura, K. Yasuda, A. Senda, H. Motoshima & T. Urashima: Effects of carbohydrate source on physicochemical properties of the exopolysaccharide produced by Lactobacillus fermentum TDS030603 in a chemically defined medium. Carbohydr. Polym., 79, 1040 (2010))

[0095] · Lactobacillus gasseri FR4 (Non-patent literature: Rizwana Parveen Rani Marimuthu Anandharaj Abraham David Ravindran: Characterization of a novel exopolysaccharide produced by Lactobacillus gasseri FR4 and demonstration of its in vitro biological properties. International Journal of Biological Macromolecules Volume 109, 1 April 2018, Pages 772 - 783.)

[0096] It should be noted that here, Lactobacillus delbrueckii subsp. bulgaricus OLL1073R - 1 was internationally deposited at the Patent Biological Depositary Center of the National Institute of Advanced Industrial Science and Technology (Central 6, Tsukuba Center, 1 - 1 - 1 Higashi, Tsukuba, Ibaraki, Japan) under the Budapest Treaty on November 29, 2006 (deposit date) with the deposit number FERM BP - 10741. It should be noted that the patent microorganism deposit service of the Patent Biological Depositary Center of the National Institute of Advanced Industrial Science and Technology was taken over by the National Institute of Advanced Industrial Science and Technology on April 1, 2012, and the International Patent Biological Depositary Center of the National Institute of Advanced Industrial Science and Technology was transferred to the National Institute of Advanced Industrial Science and Technology premises at 2 - 5 - 8 Kamigou, Kisarazu, Chiba, Japan on April 1, 2013.

[0097] 2. Periodontal disease-causing bacteria

[0098] Periodontal disease-causing bacteria (sometimes referred to as "periodontal pathogens" or "periodontal bacteria") are a general term for bacteria associated with the onset / progression of periodontal disease. As the periodontal disease-causing bacteria in the present invention, it includes Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, etc. listed in the red complex (the most important periodontal disease-causing bacteria), and oral bacteria such as Fusobacterium nucleatum. It is also known that these bacteria have a high ability to produce volatile sulfur compounds (VSCs), which are the main substances causing bad breath, in the oral cavity. The IgA increased in human saliva by the fermented milk according to the embodiment of the present invention will particularly effectively cross-react with Porphyromonas gingivalis and Fusobacterium nucleatum among the above-mentioned periodontal disease-causing bacteria.

[0099] 3. Human

[0100] Regarding the human in the embodiment of the present invention, there are no particular limitations on his / her age, gender, nationality, etc. However, the risk of suffering from periodontal disease tends to increase with age. It is said that about 70% of people over 60 years old suffer from periodontal disease. Therefore, a person over 60 years old is preferably selected.

[0101] In addition, it is said that more than 70% of pneumonia in the elderly is aspiration pneumonia. Many of the bacteria causing aspiration pneumonia are periodontal disease-causing bacteria. Therefore, the human in the present invention is preferably an elderly person. It should be noted that the World Health Organization (WHO) defines the elderly as people over 65 years old.

[0102] Furthermore, periodontal disease-causing bacteria tend to proliferate due to the decline of immune function. Therefore, a person over 65 years old with a tendency of immune function decline is preferably selected. In addition, it can be an elderly person older than 65 years old, such as a person over 70 years old, a person over 75 years old, or a person over 80 years old.

[0103] In people with a smoking habit, the periodontal disease-causing bacteria tend to increase. Therefore, the person in the embodiment of the present invention is preferably a person with a smoking habit.

[0104] In addition, periodontal disease-causing bacteria easily invade blood vessels from swollen gums and then spread throughout the body. Although the bacteria that enter the blood vessels will be eliminated by the body, it is known that endotoxins derived from periodontal disease-causing bacteria will continue to remain in the body and have an adverse effect on the blood sugar level in the body. Therefore, the person according to the embodiment of the present invention is also preferably a person in the pre-diabetic stage or a diabetic person.

[0105] 4. Fermented milk

[0106] As described above, the fermented milk in the embodiment of the present invention refers to fermented milk obtained by fermenting milk (animal milk), including, for example, "fermented milk", "lactic acid bacteria beverage", "milk beverage", "natural cheese", etc. defined in the ordinance of the Ministry of Health, Labour and Welfare regarding the composition standards of milk and dairy products (Ordinance on Milk, etc.), but is not limited to these. For example, the fermented milk refers to "fermented milk" defined in the Ordinance on Milk, etc., that is, milk such as raw milk, cow milk, special cow milk, raw goat milk, pasteurized goat milk, raw sheep milk, adjusted milk, low-fat milk, non-fat milk, and processed milk, or milk containing non-fat milk solid components equivalent to or more than these, is fermented with lactic acid bacteria or yeast to form a solid shape (hard type), paste shape (soft type), or liquid shape (beverage type), or is frozen, but is not limited thereto. In the fermented milk according to the embodiment of the present invention, the concentration range of the non-fat milk solid component is, for example, preferably in the range of 4.0% by mass or more and 12.0% by mass or less, more preferably in the range of 6.0% by mass or more and 10.0% by mass or less, and further preferably in the range of 7.0% by mass or more and 9.0% by mass or less. In addition, the concentration of the milk fat component is, for example, preferably in the range of 0.2% by mass or more and 4.0% by mass or less, more preferably in the range of 0.3% by mass or more and 3.0% by mass or less, and further preferably in the range of 0.4% by mass or more and 2.0% by mass or less. It should be noted that the fermented milk in the embodiment of the present invention may exclude the fermented product of plant milk.

[0107] As a typical example of fermented milk, yogurt can be cited. The international standard defined by the Food and Agriculture Organization of the United Nations (FAO) / World Health Organization (WHO) also stipulates that "the product called yogurt is made from dairy products such as milk and skimmed milk powder through the lactic acid fermentation of Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus, and a large number of live bacteria of the above two kinds of bacteria exist in the final product". In the present invention, "yogurt" includes the yogurt defined by the above FAO / WHO. This yogurt includes, for example, plain yogurt, hard yogurt (set yogurt), soft yogurt, yogurt beverage, etc. As the yogurt according to the embodiment of the present invention, from the viewpoints of eating feeling and satisfaction, hard yogurt is particularly preferred. In addition, when the target is an elderly person, from the viewpoint of preventing aspiration, hard yogurt is particularly preferred.

[0108] As a method for producing fermented milk according to an embodiment of the present invention, for example, there can be mentioned "a method in which raw milk is sterilized and cooled, and then a lactic acid bacterium starter containing the above-mentioned lactic acid bacteria is added to the raw milk, and the raw milk added with the lactic acid bacterium starter is fermented at a fermentation temperature and for a fermentation time that can reach a specified lactic acid acidity". Exopolysaccharides are produced by lactic acid bacteria belonging to the genus Lactobacillus during fermentation. In this method, the lactic acid acidity is, for example, 0.6 to 1.2. It should be noted that the lactic acid acidity is preferably 0.6 to 0.8. In addition, the fermentation temperature is, for example, 40 to 45°C. In addition, the fermentation time is, for example, 2 to 12 hours. It should be noted that the fermentation time is preferably 3 to 8 hours.

[0109] As the lactic acid bacterium starter, from the viewpoints of production efficiency and palatability, it is preferable to use a combination of lactic acid bacteria belonging to the genus Streptococcus or Streptococcus thermophilus and lactic acid bacteria belonging to the genus Lactobacillus. In addition, when the lactic acid bacterium belonging to the genus Lactobacillus is Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (deposit number: FERM BP-10741), the thermophilic bacterium is more preferably Streptococcus thermophilus 1131 or Streptococcus thermophilus OLS3059. It should be noted that here, "Streptococcus thermophilus OLS3059" was internationally deposited at the Patent Biological Depositary Center of the National Institute of Advanced Industrial Science and Technology (6th Central Building, Tsukuba Center, 1-1-1 Higashi, Tsukuba, Ibaraki, Japan) on November 29, 2006 (deposit date) under the accession number FERM BP-10740 based on the Budapest Treaty. It should be noted that the patent microorganism deposit business of the Patent Biological Depositary Center of the National Institute of Advanced Industrial Science and Technology was taken over by the National Institute of Advanced Industrial Science and Technology on April 1, 2012, and the International Patent Biological Depositary Center of the National Institute of Advanced Industrial Science and Technology was transferred to the National Institute of Advanced Industrial Science and Technology premises at 2-5-8 Kamigou, Kisarazu, Chiba, Japan on April 1, 2013. In addition, Streptococcus thermophilus 1131 can be obtained from Meiji Bulgarian-style yogurt "LB81" manufactured by Meiji Co., Ltd.

[0110] In addition, for the purpose of being used as a lactic acid bacterium starter or imparting functionality, etc., fermentation microorganisms such as lactic acid bacteria, lactococci, bifidobacteria, yeasts, etc. other than lactic acid bacteria belonging to the genus Lactobacillus and lactic acid bacteria belonging to the genus Streptococcus or their metabolites can also be added. These fermentation microorganisms can be live bacteria or dead bacteria that have been heat-treated, etc.

[0111] The lower limit of the amount of EPS contained in the fermented milk according to the embodiment of the present invention is preferably 0.5 mg per 100 g, more preferably 1.0 mg, further preferably 2.0 mg, still more preferably 2.5 mg, and particularly preferably 3.0 mg. On the other hand, the upper limit is not particularly limited. For example, it is preferably 100 mg per 100 g, more preferably 50 mg, further preferably 10 mg, still further preferably 7.0 mg, still more preferably 6.0 mg, and particularly preferably 4.0 mg.

[0112] The fermented milk according to the embodiment of the present invention can be easily ingested. In addition, since fermented milk has a long history of consumption and high safety, and there is no need to worry about side effects, consumers can ingest it with confidence.

[0113] By forming the fermented milk according to the embodiment of the present invention into a single-packaged form in an amount suitable for one-time ingestion, the fermented milk according to the embodiment of the present invention can be appropriately and easily ingested, which is preferable in terms of usability. Although the amount suitable for one-time ingestion varies among individuals, when the fermented milk has a non-fat milk solid content of 8.0% by mass, it is preferably in the range of 10 mL or more and 1000 mL or less, more preferably in the range of 30 mL or more and 500 mL or less, further preferably in the range of 50 mL or more and 200 mL or less, and preferably 80 mL or more and 120 mL or less each time. Alternatively, it is preferably in the range of 10 g or more and 1000 g or less, preferably in the range of 30 g or more and 500 g or less, preferably in the range of 50 g or more and 200 g or less, more preferably in the range of 80 g or more and 150 g or less, and further preferably in the range of 100 g or more and 120 g or less each time.

[0114] In the embodiment of the present invention, the "single-packaged form" includes all forms, such as conventional packaging methods like containers with lids, bottles with lids, stand-alone bags, sachets, tubes, etc. In the embodiment of the present invention, by recording instructions such as the uses, effects, and ingestion methods of the fermented milk according to the embodiment of the present invention on each individual package or a package containing multiple individual packages, and / or enclosing an item with the instructions recorded therein, and / or additionally posting an item such as a manual with the instructions recorded thereon, the uses can be clarified.

[0115] From the viewpoint of improving the effect of preventing the proliferation of periodontal disease pathogens, it is preferred to continue to ingest the fermented milk of the embodiment of the present invention for more than 3 days, preferably for more than 5 days, preferably for more than 1 week, preferably for more than 2 weeks, preferably for more than 4 weeks, more preferably for more than 6 weeks, further preferably for more than 8 weeks, further preferably for more than 10 weeks, further preferably for more than 12 weeks, further preferably for more than 24 weeks, and particularly preferably for more than 36 weeks. It should be noted that the fermented milk of the embodiment of the present invention has sufficient edible experience and can be safely ingested, so the upper limit of the ingestion period is not particularly limited, and can be permanently continued. If an upper limit must be set, for example, it is less than 60 weeks. It should be noted that the upper limit can be set to less than 120 weeks, less than 100 weeks, or less than 80 weeks. It should be noted that as a mode of ingestion, oral ingestion is preferred.

[0116] In addition, it is preferred that the fermented milk of the embodiment of the present invention is labeled with instructions on its use, efficacy, function, type of active ingredients, method of use, etc. The "labeling" mentioned here includes all labels for making people in need aware of the above-mentioned effects. The labeling can be any labeling that can be imagined or inferred from the above-mentioned labeling content, and may include all labels that are not limited to the purpose of the labeling, the content of the labeling, and what the object / medium to be labeled is. Examples include marking the above-mentioned instructions on the packaging / container of the product, marking the above-mentioned instructions on advertisements / price lists or transaction documents related to the product and displaying or publishing them, or providing information with these contents through electromagnetic methods (Internet, etc.).

[0117] It is preferred to add labels such as "Increase IgA in saliva that crosses with periodontal disease pathogens", "Maintain oral health", "Improve oral environment", "Maintain or improve oral health", "Maintain or improve oral health and overall health" to the product packaged with fermented milk according to an embodiment of the present invention.

[0118] It should be noted that the expressions used for the above-mentioned indication are not limited to the above-mentioned examples, and may be expressions with the same meaning as the above-mentioned examples. As such expressions, for example, various expressions such as "increasing IgA in saliva", "increasing IgA against periodontal disease pathogens in saliva", "preventing the occurrence of bad breath", "reducing bad breath" are all acceptable to those in need.

[0119] In addition, the proliferation of periodontal disease-causing bacteria represented by Porphyromonas gingivalis has also been pointed out to be related to the onset of rheumatoid arthritis. In addition, as diseases caused by periodontal disease-causing bacteria other than this, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease, arthritis, etc. are known. The fermented milk according to the embodiment of the present invention increases IgA that cross-reacts with periodontal disease-causing bacteria, inhibits the colonization and proliferation of these bacteria, and can not only prevent these bacteria from invading the lungs or blood vessels and spreading throughout the body, releasing endotoxins throughout the body, but also maintain or improve oral health, and can also bring great effects to overall health, such as reducing the risk of contracting the above diseases or preventing the aggravation of the disease.

[0120] It should be noted that the above fermented milk can also be made into forms such as special-purpose foods, comprehensive nutritional foods, nutritional supplements, foods for specified health use, functional labeled foods, processed foods, etc. In addition, the fermented milk can also be blended into compositions such as beverages other than drinkable yogurt, liquid foods, etc. In addition, the fermented milk can also be used after being subjected to drying treatment, concentration treatment, etc.

[0121] Hereinafter, the present invention will be described more specifically based on examples and comparative examples. It should be noted that the examples do not limit the present invention.

[0122] Examples

[0123] (Test examples)

[0124] - Test samples -

[0125] The following test was carried out using Meiji Probio yogurt R-1 hard type manufactured by Meiji Co., Ltd. (each 112 g contains 3.3 mg or more of R-1 lactic acid bacteria EPS. It should be noted that usually each 112 g contains about 5.0 mg of R-1 lactic acid bacteria EPS.). It should be noted that this hard yogurt is obtained by fermenting milk with Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (FERM BP-10741) and Streptococcus thermophilus. Here, Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (FERM BP-10741) is a lactic acid bacterium capable of producing exopolysaccharides. And this hard yogurt contains exopolysaccharides produced by OLL1073R-1 (FERM BP-10741). In addition, since this hard yogurt was put on the market in 2009, it has achieved sufficient sales results, and no serious side effects considered to be caused by this product have been reported in the past.

[0126] - Test methods -

[0127] For several consecutive years, the above-mentioned Meiji Probio yogurt R-1 hard type was provided to Special Nursing Home A, and most of the residents consumed 1 (112 g) per day continuously. Forty-seven residents of Special Nursing Home A (among them, 4 did not consume the above-mentioned Meiji Probio yogurt R-1 hard type) and 52 residents of Nursing Care Welfare Facility B, where the above-mentioned Meiji Probio yogurt R-1 hard type was not provided, were selected as the analysis subjects. In addition, the analysis subjects were divided into a yogurt intake group of 43 people (aged 76 to 102 years (average age 87 years)) and a non-intake group (aged 74 to 99 years (average age 90 years)). Then, 4 years and 8 months after the above-mentioned Meiji Probio yogurt R-1 hard type was provided to Special Nursing Home A, saliva and tongue coatings were collected from the residents of each nursing home, and the saliva secretion rate was measured. For saliva, a saliva collection kit (Salikids) with a thin string on a cotton roll was used, and one subject was paired with one dentist and one oral hygienist to collect saliva, with the collection time being at most 5 minutes (1 minute to 5 minutes, varying from person to person). For the tongue coating, a dentist / oral hygienist used a dedicated cotton swab (swab) to collect the tongue coating.

[0128] (Measurement of IgA secretion rate)

[0129] Next, the total IgA concentration in each collected saliva was measured, and the IgA concentration in the saliva cross-reacting with Porphyromonas gingivalis (hereinafter sometimes referred to as "Pg") and Fusobacterium nucleatum (hereinafter sometimes referred to as "Fn"), which are oral resident bacteria, was measured according to the ELISA method. The IgA secretion rate for each was calculated by multiplying the value of the above-mentioned IgA concentration by the saliva secretion rate. It should be noted that the IgA secretion rate cross-reacting with each bacterium is a value obtained by multiplying the absorbance obtained by the ELISA method by the saliva secretion rate (Arbitrary units (hereinafter sometimes referred to as "AU")). Taking the average value of the residents of Nursing Care Welfare Facility B as 1 AU, it is expressed by its relative value (AU).

[0130] It should be noted that the method for measuring the IgA concentration in saliva cross-reacting with Pg and Fn based on the ELISA method is as follows.

[0131] (1) Reagents / equipment

[0132] · ELISAStarter Accessory Package Kit I (Bethyl Laboratories#E101)

[0133] · ELISA Stop Solution (Bethyl Laboratories #E115)

[0134] · Biotinylation Kit (Sulfo-OSu; Dojindo #BK01)

[0135] · Goat Anti-Human IgA (Bethyl Laboratories #A80-102A)

[0136] · Streptavidin-HRP Solution (Abcam #ab210901)

[0137] · Antigen: Porphyromonas gingivalis ATCC33277 (Pg), live bacteria

[0138] · Antigen: Fusobacterium nucleatum ATCC25586 (Fn), live bacteria

[0139] (2) ELISA Procedure

[0140] (2-1) Antigen Solid Phase Immobilization

[0141] Suspend each of the above antigens in the coating buffer in the ELISAStarter Accessory Package Kit I (hereinafter sometimes referred to as the "kit") so that the optical density (OD) is 1.0. Then, inject 100 μL of this solution into each well of the 96-well plate in the kit. Then, leave the 96-well plate at 4 °C overnight. It should be noted that wells without antigen were also prepared to confirm non-specific reactions.

[0142] (2-2) Blocking

[0143] After washing the 96-well plate immobilized with antigen 3 times with the washing solution in the kit, inject 200 μL of the blocking buffer in the kit into each well of the 96-well plate. Then, leave the 96-well plate at 25 °C for 30 minutes.

[0144] (2-3) Primary Antibody Reaction

[0145] Add Tween 20 to the blocking buffer in the kit at a final concentration of 0.05% to prepare a dilution solution. After washing the blocked 96-well plate 3 times with the washing solution in the kit, inject 100 μL of saliva diluted with the dilution solution into each well of the 96-well plate. Then, leave the 96-well plate at 25 °C for 1 hour.

[0146] (2-4) Secondary Antibody Reaction

[0147] Biotinylate goat anti-human IgA using a biotinylation kit to prepare biotinylated anti-human IgA. After washing the 96-well plate treated with the primary antibody 4 times with the washing solution in the kit, add 100 μL of biotinylated anti-human IgA diluted to 1 μg / mL with the diluent to each well of the 96-well plate. Then, let the 96-well plate stand at 25 °C for 1 hour.

[0148] (2-5) Avidin-biotin binding reaction

[0149] After washing the 96-well plate treated with the secondary antibody 4 times with the washing solution in the kit, add 100 μL of streptavidin-HRP solution diluted 10,000-fold with the diluent to each well of the 96-well plate. Then, let the 96-well plate stand at 25 °C for 1 hour.

[0150] (2-6) Luminescence / detection

[0151] After washing the 96-well plate treated with the secondary antibody 4 times with the washing solution, add 100 μL of the enzyme substrate in the kit to each well of the 96-well plate. Let the 96-well plate stand in the dark at 25 °C for 15 minutes, and then add 100 μL of ELISA stop solution to each well to stop the reaction in each well. Finally, measure the optical density (OD) of the samples in each well at 450 nm.

[0152] -Statistical methods for various data-

[0153] Analyze the inter-group differences in IgA secretion rate using the Mann-Whitney U test.

[0154] (Analysis of the flora in the tongue coating)

[0155] Cut the tip of the swab that has collected the tongue coating (hereinafter referred to as "sample".) into a microcentrifuge tube containing zirconia beads ( 0.3 g), and add Buffer ASL (Qiagen) to the microcentrifuge tube. Then, heat the microcentrifuge tube at 95 °C for 15 minutes using a block heater to extract DNA from the sample in the microcentrifuge tube. Use the QIAamp DNA Stool Mini kit (Qiagen) and perform DNA extraction according to a modified method that shortens the bead disruption time in the method described in the following reference 5 (method of protocol Q) to 4 minutes. Then, use Index PCR (Nextera XT index kit v2 (Illumina)), using the DNA obtained by the above method as a template, and use the primer (5’-TCGTCGGCAGCGTCAGATGTGTATAAGAGACAGCCTACGGGNGGC WGCAG-3’

[0156] The V3-V4 region of the 16S rRNA gene was amplified using (5’-GTCTCGTGGGCTCGGAGATGTGTATAAGAGACAGGACTACHVGGGTATCTAATCC-3’). The amplification of DNA based on this Index PCR was performed according to the manufacturer's recommended method of (Nextera XT index kit v2 (Illumina)) (the method described in Reference 6 shown below). Then, the DNA amplification product obtained by the above method was purified using AMPure. After measuring the DNA concentration of the purified DNA amplification product using the Quant-iT dsDNA High-Sensitivity Assay Kit, a sequencing library was prepared. Here, the reagents and methods for preparing the sequencing library were all implemented according to the protocol provided by Illumina (the methods described in References 6 and 7 shown below). Then, using the obtained sequencing library and the MiSeq Reagent kit v3 (600 cycle) (Illumina Inc., California, U.S.), DNA sequencing of the DNA amplification product was performed using the MiSeq (Illumina). Next, using the data obtained from the above DNA sequencing, OTU (operational taxonomic unit) creation and analysis of bacterial species and genera were performed using the data analysis software, namely the pipeline QIIME2 (https: / / qiime2.org / ), and the presence ratio of Fusobacterium nucleatum subsp. nucleatum in the tongue coating was calculated, and the correlation between the presence ratio of Fn in the tongue coating flora and the IgA secretion rate in saliva that cross-reacts with Fn was investigated.

[0157] Reference 5: Costea PI.et al.Towards stanards for human feacal sampleprocessing in metagenomic studies.Nat Biotechnol.2017,35(11),1069-1076.

[0158] Reference 6: 16S Metagenomic Sequencing Library Preparation(15044223B)

[0159] Reference 7: Quick Reference Guide For Miseq Control Software2.6

[0160] -Test Results-

[0161] As Figure 1 shown, the secretion rate of IgA in saliva cross-reacting with Pg and Fn in the yogurt intake group was significantly higher than that in the non-intake group. It should be noted that the p-values for Pg and Fn were less than 0.05 (p < 0.05). Therefore, it was confirmed that Meiji Probio yogurt R-1 hard type increased IgA in human saliva cross-reacting with periodontal disease pathogens. Thus, by ingesting Meiji Probio yogurt R-1 hard type, it is expected to inhibit the colonization and proliferation of periodontal disease pathogens represented by Porphyromonas gingivalis in the oral cavity, and reduce the risks of onset of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease, and arthritis, and prevent the aggravation of these symptoms. In addition, as Figure 2 shown, there was a significant negative correlation (p < 0.05) between the presence ratio of Fn in the tongue coating flora and the secretion rate of IgA in saliva cross-reacting with Fn. Therefore, it can be considered that in the group with a high secretion rate of IgA in saliva cross-reacting with Fn, the presence ratio of Fn in the oral flora decreases. This indicates that Meiji Probio yogurt R-1 hard type can reduce the number and presence ratio of periodontal disease pathogens and maintain or improve the oral health of humans.

[0162] Industrial Applicability

[0163] The fermented milk of the present invention can increase IgA in human saliva cross-reacting with periodontal disease pathogens, and thus can maintain or improve oral health. Therefore, ingesting the fermented milk of the present invention helps prevent major diseases such as systemic diseases, aspiration pneumonia, and cancer caused by the increase of periodontal disease pathogens, and further helps improve the quality of life (QOL: Quality of life).

[0164] Deposit Number

[0165] FERM BP-10741

[0166] FERM BP-10740

[0167]

[0168]

Claims

1. A fermented milk for increasing IgA cross-reactive with periodontal disease pathogens in human saliva, which contains lactic acid bacteria of the genus Lactobacillus.

2. The fermented milk according to claim 1, wherein, The lactic acid bacteria of the genus Lactobacillus are lactic acid bacteria of the genus Lactobacillus that can produce exopolysaccharides.

3. The fermented milk according to claim 2, which is obtained by fermenting milk raw materials with the lactic acid bacteria of the genus Lactobacillus that can produce exopolysaccharides.

4. The fermented milk according to claim 1, wherein The lactic acid bacteria of the genus Lactobacillus are Lactobacillus delbrueckii subsp. bulgaricus.

5. The fermented milk according to claim 4, wherein, The Lactobacillus delbrueckii subsp. bulgaricus is Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (FERM BP-10741).

6. The fermented milk according to claim 5, which further contains Streptococcus thermophilus.

7. The fermented milk according to claim 1, wherein, The periodontal disease pathogen is Porphyromonas gingivalis.

8. The fermented milk according to claim 1, wherein, The periodontal disease pathogen is Fusobacterium nucleatum.

9. The fermented milk according to claim 1, wherein, The person is an elderly person.

10. The fermented milk according to claim 9, wherein, The elderly person is a person over 65 years old.

11. A fermented milk for maintaining or improving oral health, which contains lactic acid bacteria of the genus Lactobacillus.

12. The fermented milk according to claim 11, wherein, The maintenance or improvement of oral health is to inhibit the increase in the number of periodontal disease pathogens or reduce the number of periodontal disease pathogens.

13. The fermented milk according to claim 12, wherein, The number of periodontal disease pathogens is the number of Porphyromonas gingivalis.

14. The fermented milk according to claim 12, wherein, The number of periodontal disease pathogens is the number of Fusobacterium nucleatum.

15. A fermented milk for reducing the risk of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis, which contains lactic acid bacteria of the genus Lactobacillus.

16. A fermented milk for preventing the exacerbation of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis, which contains lactic acid bacteria of the genus Lactobacillus.

17. The fermented milk according to claim 15 or 16, which is achieved by increasing IgA cross-reactive with periodontal disease pathogens.

18. A food composition for increasing IgA cross-reactive with periodontal disease pathogens in human saliva, which uses the fermented milk according to any one of claims 1 to 10 as an active ingredient.

19. A food composition for maintaining or improving oral health, which uses the fermented milk according to any one of claims 11 to 14 as an active ingredient.

20. A food composition for reducing the risk of developing rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis, which uses the fermented milk described in claim 15 as an active ingredient.

21. A food composition for preventing the exacerbation of rheumatoid arthritis, bacterial pneumonia, bacterial endocarditis, diabetes, arteriosclerosis, myocardial infarction, thromboangiitis obliterans, premature / low birth weight infants, AIDS (activation of latent HIV infection), cancer, osteoporosis, obesity, metabolic syndrome, kidney disease or arthritis, which uses the fermented milk described in claim 16 as an active ingredient.

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