SACCHAROMYCES CEREVISIAE VAR BOULARDII STRAIN FOR THE TREATMENT OF ORAL CAVITY INFECTION

Description

Domaine de l'Invention

[0001] The present invention relates to the field of oral health. The invention relates more particularly to a strain Saccharomyces cerevisiae var boulardii specific, used alone or in combination with a yeast Saccharomyces cerevisiae dry inactivated, in the treatment and / or prevention of infectious diseases of the oral cavity such as dental caries and periodontal diseases. Contexte de l'Invention

[0002] In humans, the oral cavity is a complex ecosystem, open to the interior, inhabited by numerous microorganisms including more than 700 bacterial species detected (Ghannoum et al., PLoS Pathog., 2010; 6: e1000713; Marsh et al., Periodontol., 2000, 55: 16-35; Paster et al., Periodontol., 2000, 42: 80-87). For the same individual, the number of resident bacterial species varies from 150 to 250. Most of these species are commensal and necessary to maintain the balance of this ecosystem. However, in certain situations (high carbohydrate intake, tobacco use, or physiological changes such as aging, puberty or pregnancy, etc.), a disruption of this balance occurs and can lead to the development of infectious diseases of the oral cavity.

[0003] The main infectious diseases of the oral cavity are dental caries and periodontal disease. Dental caries is a polybacterial disease that manifests itself by demineralization of the hard tissues of the tooth. This demineralization is due to the production of acids by fermentative bacteria present in dental plaque. Streptococci of the group mutans and Lactobacilli are considered the main cariogenic bacteria. The World Health Organization (WHO) report on oral health notes the high prevalence of caries, especially among young people. Compared to the rest of the world, the risk of caries during childhood is much higher in developed countries (North America, Australia, Europe, Japan), due to a diet very rich in sugar in these countries.

[0004] Periodontal diseases are a group of pathologies affecting the periodontium (i.e., the supporting tissues of the tooth - bone and gingival mucosa). These diseases are divided into two broad categories: gingivitis and periodontitis. Gingivitis corresponds to any inflammation limited to the superficial periodontium. Periodontitis is an advanced infectious lesion of the periodontium and often follows gingivitis. The presence of certain bacteria and an intense inflammatory response lead to the destruction of the periodontium. The transition from a healthy state to a state of periodontal disease is accompanied by a progressive transition to a flora richer in anaerobic bacteria and Gram-negative bacteria. This phenomenon is called anaerobic drift. Among the bacterial species most frequently involved in periodontal disease are: Fusobacterium nucleatum And Porphyromonas gingivalis whose co-aggregation appears to enhance their survival and pathogenicity (Diaz et al., Microbiology, 2002, 148: 467-472; Saito et al., FEMS Immunol. Med. Microbiol., 2008, 54: 349-355; Polak et al., J. Clin. Periodontol., 2009, 36: 406-410).

[0005] The treatment of tooth decay, which only affects the enamel or dentin, includes a filling with a composite or silver amalgam. When the tooth is severely damaged, the dentist will restore it with a crown; and if the nerve is affected, a root canal treatment must be performed. Untreated decay continues to progress and bacteria eventually attack the alveolar bone under the root, leading to a painful abscess that must be treated with antibiotics and then mechanical treatment. Antibiotics are also used in the treatment of periodontal disease in combination with scaling and root planing, curettage, dental surgery, or as a stand-alone treatment to reduce bacteria before and / or after these common periodontal procedures.

[0006] The intensive use of antibiotics has introduced a selection pressure leading to the worrying development of populations of antibiotic-resistant microorganisms and a general decline in therapeutic efficacy. Initially punctual, these resistances have become massive and worrying. Some bacterial strains have become multi-resistant, i.e., resistant to several antibiotics, and other strains have become toto-resistant, i.e., resistant to all available antibiotics. The latter case is fortunately still rare, but the phenomenon is increasing and places doctors in a therapeutic impasse. Thus, in the current context of growing and worrying antibiotic resistance, scientists and health professionals are seeking to identify new therapeutic strategies, including in the treatment and / or prevention of infectious diseases of the oral cavity.

[0007] EP 1 852 122 A1 describes compositions comprising Saccharomyces cerevisiae var. boulardii, alone or in combination with Enterococcus faecium, to treat diseases of the oral cavity. Yeasts work by inhibiting pathogenic bacteria, such as Prévotella intermedia And Porpyhromona gingivalis, and restoring the balance of the microflora in the oral tissues. Diseases treated include, for example, ginvivitis and periodontitis. Résumé de l'Invention

[0008] The present inventors have surprisingly found that yeast strains Saccharomyces cerevisiae var. boulardii, such as yeast strain Saccharomyces cerevisiae var. boulardii filed by the Applicant on August 21, 2007 with the CNCM (National Collection of Cultures of Microorganisms, 25 rue du Docteur Roux, 75724 Paris Cedex, 15, France) under number I-3799, had an increased capacity, compared to other probiotics, to inhibit the growth of periodontopathogenic and cariogenic agents.

[0009] The present inventors have also demonstrated a synergy between a yeast strain Saccharomyces cerevisiae var. boulardii and a yeast strain Saccharomyces cerevisiae in dry and inactivated form, to significantly inhibit the growth of certain periodontal and cariogenic pathogens. Such a yeast strain Saccharomyces cerevisiae var. boulardii is, for example, strain number I-3799 already described above. Such a yeast strain Saccharomyces cerevisiae is, for example, the strain Saccharomyces cerevisiae filed by the Applicant on October 17, 2007 with the CNCM under number I-3856.

[0010] The present invention thus relates to the yeast strain Saccharomyces cerevisiae var boulardii filed on August 21, 2007, with the CNCM under number I-3799, or a combination of a yeast strain Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain Saccharomyces cerevisiae, for use in the prevention and / or treatment of an infectious disease of the oral cavity in a subject, characterized in that the infectious disease is dental caries, gingivitis or periodontitis.

[0011] In some embodiments, the yeast Saccharomyces cerevisiae var boulardii I-3799 or the yeast strain Saccharomyces cerevisiae var boulardii of the combination is found in live dry form.

[0012] In some embodiments, the yeast strain Saccharomyces cerevisiae var boulardii of the combination is the strain filed, on August 21, 2007, with the CNCM under number I-3799.

[0013] In some embodiments, the yeast strain Saccharomyces cerevisiae is the strain filed on October 17, 2007 with the CNCM under number I-3856.

[0014] In some embodiments, the yeast strain Saccharomyces cerevisiae var boulardii I-3799, or the combination of a yeast strain Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain Saccharomyces cerevisiae, as defined above, is included in a food supplement.

[0015] In some embodiments, the dietary supplement is in the form of a lozenge, candy, chewing gum, orally dispersible or water-dilutable powder in the form of a stick or sachet, a lozenge or chewable tablet, chewing gum, capsule, tablet, drops, or a vial with a measuring cap.

[0016] In some embodiments, the yeast strain Saccharomyces cerevisiae var boulardii I-3799, or the combination of a yeast strain Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain Saccharomyces cerevisiae, as defined above, is included in a parapharmaceutical or cosmetic composition.

[0017] In certain embodiments, the parapharmaceutical or cosmetic composition is in the form of a toothpaste, a mouthwash, an oral spray, an oral cream or gel, an orodispersible sheet, a powder intended to be sprinkled directly into the oral cavity, an orodispersible powder or to be diluted in water in the form of a stick or sachet, or a vial with a measuring cap.

[0018] In some embodiments, the yeast strain Saccharomyces cerevisiae var boulardii I-3799 or the combination of a yeast strain Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain Saccharomyces cerevisiae is included in a pharmaceutical composition, the pharmaceutical composition comprising an effective amount of the yeast strain Saccharomyces cerevisiae var boulardii, I-3799 or the combination, as defined above, and at least one physiologically acceptable excipient.

[0019] In some embodiments, the pharmaceutical composition is for topical administration or oral administration.

[0020] In some embodiments, the pharmaceutical composition further comprises at least one additional pharmaceutical active ingredient having soothing, anti-irritant, analgesic, painkiller, anti-inflammatory, healing, antibiotic, antipyretic, or antifungal activity.

[0021] In some embodiments, the yeast strain Saccharomyces cerevisiae var boulardii I-3799 or the combination of a yeast strain Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain Saccharomyces cerevisiae is included in a dental medical device.

[0022] In some embodiments, the dental appliance is a dental implant, a dental crown, a dental bridge, a dental onlay, or a dental prosthesis.

[0023] In some embodiments, the infectious disease of the oral cavity is induced by periodontopathogenic bacteria and / or cariopathogenic bacteria.

[0024] In some embodiments, the periodontopathogenic bacteria are selected from Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum ) , Porphyromonas gingivalis, Prevotella intermedia, and / or the cariopathogenic bacteria is Streptococcus mutans.

[0025] In some embodiments, the infectious disease of the oral cavity to be prevented or treated according to the present invention is a side effect of a medical treatment, or is present or likely to develop or recur in a patient suffering from an immunodeficiency, or is present in a pregnant woman, an elderly person, a child or a patient with a hyper-inflammatory phenotype.

[0026] A more detailed description of certain preferred embodiments of the invention is given below. Description Détaillée de l'Invention

[0027] As mentioned above, the present invention relates to a yeast strain Saccharomyces cerevisiae var boulardii having the ability to inhibit the growth of periodontopathogenic and cariogenic agents and its use, alone or in combination with a yeast Saccharomyces cerevisiae dry and inactivated, in the treatment and / or prevention of infectious diseases of the oral cavity. I - Yeast Strain Saccharomyces cerevisiae var boulardii

[0028] The term "yeast strain" refers to a relatively homogeneous population of yeast cells. A yeast strain is obtained from a clone, a clone being a population of cells obtained from a single yeast cell.

[0029] A strain of yeast Saccharomyces cerevisiae var boulardii which can be used in the context of the present invention is, for example, the strain which was deposited on August 21, 2007, by the present Depositor, at the CNCM (National Collection of Cultures of Microorganisms, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France) under number I-3799.

[0030] This strain Saccharomyces cerevisiae var boulardii has previously been described, by the present Applicant himself, in document WO 2009 / 103884, where it is presented as being useful in the prevention and / or treatment of pathologies, disorders or disorders of the intestine.

[0031] In the context of the present invention, a yeast strain Saccharomyces cerevisiae var boulardii is found in the form of yeast cells obtained by culturing (or multiplying) the starting strain. Cultivating a strain Saccharomyces cerevisiae var boulardii can be carried out by any suitable method. The methods of cultivating a strain Saccharomyces cerevisiae var boulardii are known in the art, and those skilled in the art know how to optimize the culture conditions for each strain according to its nature. Yeast cells can, for example, be obtained by multiplying a strain Saccharomyces cerevisiae var boulardii in a culture medium as described in the reference work "Yeast Technology", 2nd Edition, 1991, Reed and Nagodawithana, published by Van Nostrand Reinhold (ISBN 0-442-31892-8).

[0032] So, for example, on an industrial scale, yeast Saccharomyces cerevisiae var boulardii, usable in the context of the present invention, can be obtained by a method comprising the following steps: cultivation of a strain Saccharomyces cerevisiae var boulardii (for example strain number I-3799) in a culture medium in several stages, first in semi-anaerobiosis, then in aerobiosis (oxygen-rich medium / atmosphere) to obtain a multiplication of the starting yeast cells; and separation, by centrifugation, of the yeast cells thus produced to obtain a liquid yeast cream containing between 12% and 25% of dry yeast matter.

[0033] Yeast Saccharomyces cerevisiae var boulardii used in the context of the invention is in the form of live yeast. The term "live yeast", which is synonymous with "active yeast", refers to a population of yeast cells that are metabolically active.

[0034] The live yeast used in the context of the present invention is in the form of a dry yeast. A dry yeast is characterized by a low water content, and generally comprises a yeast dry matter content greater than 90%, preferably a dry matter content of between 92% and 98%, for example a dry matter content of between 94.5% and 96.5%. One of the advantages of a dry yeast is its long shelf life.

[0035] So the yeast production process Saccharomyces cerevisiae var boulardii may further comprise a subsequent drying step, to obtain a yeast in dry form. This drying step may or may not be followed by a grinding operation. The drying may, for example, be freeze-drying, fluidized bed drying, drum drying or spray drying. In the case of freeze-drying, a maltodextrin or lactose type carrier may be used. II - Combination of Yeast Strain Saccharomyces cerevisiae var boulardii and the Yeast Strain Saccharomyces cerevisiae Dry Inactivated

[0036] As indicated above, the present inventors have demonstrated a synergy between a yeast strain Saccharomyces cerevisiae var. boulardii (e.g. yeast strain Saccharomyces cerevisiae var. boulardii number I-3799) and a yeast strain Saccharomyces cerevisiae in inactivated dry form to significantly inhibit the growth of periodontogenic and cariogenic bacteria. The terms "synergy" and "synergistic action," which are used interchangeably herein, refer to a coordinated action of the two yeast strains creating an effect greater than the sum of the effects expected if they had operated independently, or creating an effect that each of them could not have achieved by acting in isolation.

[0037] Yeast Saccharomyces cerevisiae used in combination with yeast Saccharomyces cerevisiae var. boulardii is an inactivated dry yeast. The terms "inactivated yeast" and "deactivated yeast", which are used interchangeably herein, refer to a yeast that is no longer alive, i.e., a yeast whose metabolism has irremediably stopped. An inactivated yeast according to the invention may be obtained by any suitable method. Suitable techniques well known to those skilled in the art include heat treatment of the yeast, spray treatment, drum drying, or any combination of these treatments. An inactivated yeast is generally in dry form. A dry yeast is characterized by a low water content, and generally comprises a yeast solids content greater than 90%, preferably a solids content of between 92% and 98%, for example a solids content of between 94.5% and 96.5%. One of the advantages of a dry yeast is its long shelf life.

[0038] The yeast strain Saccharomyces cerevisiae var. boulardii used in the combination can be any yeast strain Saccharomyces cerevisiae var. boulardii.

[0039] The yeast strain Saccharomyces cerevisiae dry inactivated used in the combination can be any strain Saccharomyces cerevisiae.

[0040] In certain particular embodiments, the yeast strain Saccharomyces cerevisiae, used in inactivated dry form in the context of the invention in combination with a strain Saccharomyces cerevisiae var boulardii, is the strain Saccharomyces cerevisiae filed on October 17, 2007, with the CNCM under number I-3856. This strain Saccharomyces cerevisiae has previously been described, by the present Applicant himself, in document WO 2009 / 103884, where it is presented as being useful in the prevention and / or treatment of pathologies, disorders or disorders of the intestine; and in document WO 2014 / 009656, where it is presented as being effective in controlling vaginal proliferation of Candida and to prevent the recurrence of vaginal or vulvovaginal candidiasis.

[0041] In certain particular embodiments, the yeast strain Saccharomyces cerevisiae var. boulardii, used in the context of the invention in combination with the yeast strain Saccharomyces cerevisiae in inactivated dry form is the yeast strain Saccharomyces cerevisiae var boulardii filed on August 21, 2007, with the CNCM under number I-3799.

[0042] The term "combination" as used herein means a mixture of Saccharomyces cerevisiae var boulardii (for example strain number I-3799) and Saccharomyces cerevisiae in inactivated dry form (e.g. strain number I-3856). The mixture may be prepared in any proportions. Thus, preferably, the combination comprises a ratio of Saccharomyces cerevisiae var boulardii I-3799: Saccharomyces cerevisiae in inactivated dry form ranging from about 90:10 (w / w = weight / weight) to about 10:90 (w / w). Thus, the ratio of Saccharomyces cerevisiae var boulardii I-3799: Saccharomyces cerevisiae in dry inactivated form may, for example, be about 90:10 (w / w), about 80:20 (w / w), about 70:30 (w / w), about 60:40 (w / w), about 50:50 (w / w), about 40:60 (w / w), about 30:70 (w / w), about 20:80 (w / w) or about 10:90 (w / w). The term "about," as used herein with reference to a number, generally includes numbers that fall within 10% in either direction of the number (above or below the number), except where that number exceeds 100% of a possible value.

[0043] In certain particular embodiments of the invention, the ratio of Saccharomyces cerevisiae var boulardii I-3799: Saccharomyces cerevisiae I-3856 in dry inactivated form is approximately 50:50 (w / w). III - Uses of the Yeast Strain Saccharomyces cerevisiae var boulardii and the Combination in the Treatment and / or Prevention of Infectious Diseases of the Oral Cavity

[0044] The invention therefore relates to the yeast strain Saccharomyces cerevisiae var boulardii number I-3799 or a combination of a yeast strain Saccharomyces cerevisiae var bourlardii (e.g. strain number I-3799) with the inactivated dry form of a strain Saccharomyces cerevisiae (e.g. strain number I-3856), for the treatment and / or prevention of infectious diseases of the oral cavity. Also described herein is a method of treating and / or preventing an infectious disease of the oral cavity in a subject, the method comprising a step of administering to the subject an effective amount of the strain Saccharomyces cerevisiae number I-3799, or a combination of a strain of yeast Saccharomyces cerevisiae var bourlardii (e.g. strain number I-3799) with the inactivated dry form of a strain Saccharomyces cerevisiae (e.g. strain number I-3856). The invention also relates to the use of the strain Saccharomyces cerevisiae var boulardii number I-3799, or a combination of a yeast strain Saccharomyces cerevisiae var bourlardii (e.g. strain number I-3799) with the inactivated dry form of a strain Saccharomyces cerevisiae(e.g. strain number I-3856), for the manufacture of a medicament for the treatment and / or prevention of infectious diseases of the oral cavity.

[0045] In the context of the present invention, "treatment" means a method which aims to: (1) delay or prevent the onset of a disease or clinical condition; (2) slow down or stop the progression, aggravation or deterioration of the symptoms of the disease; (3) bring about improvements in the symptoms of the disease; and / or (4) cure the disease. A treatment may be administered before the onset of the disease, for a prophylactic action (in which case it is called "prevention"), or it may be administered after the initiation of the disease, for a therapeutic action.

[0046] The term "subject" here refers to a mammal, and more specifically a human being, who has the potential to be a victim of an oral infection but who does not necessarily have such an infection. The term "subject" does not designate a particular age and therefore includes newborns, children, adolescents, adults, and the elderly. The term "patient" is sometimes used here, instead of "subject", when the subject is suffering from (i.e., has been diagnosed as suffering from) an infectious disease of the oral cavity.

[0047] The term "oral infectious disease" refers to a medical condition located in the mouth, resulting from infection by a pathogenic microorganism. Infectious diseases of the oral cavity include dental caries and periodontal disease.

[0048] Dental caries or tooth decay is an infectious disease of the tooth that causes damage to the enamel, dentin, and / or pulp / cementum. Cariogenic bacteria, that is, bacteria that promote the development of caries, include: Streptococcus mutans (which promotes caries of smooth and proximal surfaces); the Streptococcus mutans and lactobacilli (which promote groove caries); Actinomycetes viscosus and the Actinomycetes naeslundi (which promote root caries and colonization of dentin and the root); and lactobacilli (which promote colonization of dentin and the root). Colonization of teeth begins with streptococci, then actinomycetes and finally, lactobacilli. Bacterial predominance varies depending on the depth of the lesion. Streptococcus mutans is associated with initial lesions, while lactobacilli appear later in a deep lesion. The following pathogens are also known to be linked to the occurrence of dental caries: Streptococcus sobrinus and the Lactobacilles.

[0049] Periodontal diseases refer to diseases and pathological conditions affecting the tissues that support the teeth, namely the bone and gums. These are infections caused by the accumulation of pathogenic bacteria and their toxins on the gum line around the teeth. The main periodontal diseases are gingivitis and periodontitis. Gingivitis is the inflammation of the gums around the teeth. This condition is reversible when treated. Periodontitis, on the other hand, is a more severe pathology that deteriorates the gums and the bone that supports the teeth. The following bacteria, for example, are also known to be linked to the occurrence of periodontal diseases: Porphyromonas gingivalis, Treponema denticola, Tannerella forsythensis, Aggregatibacter actinomycetemcomitans, Actinobacillus actinomycetemcomitans, Actinomycetes odontolyticus, Actinomycetes naeslundii, Fusobacterium Nucleatum, Campylobacter rectus, Peptostreptococcus micros, Prevotella melaninogenica, Prevotella intermedia, Capnocytophaga, Eikenella, Bacteroidetes, Eubacterium saphenum, P. endodontalis, Prevotella denticola, Parvimonas micra, Filifactor alocis, species Desulfobulus and species Synergistetes.

[0050] According to Guerra's meta-analysis et al., 600 bacterial species have been identified in the human oral microbiome. However, 53% of oral microbiome species have not yet been identified and 35% are not culturable.

[0051] A method of treating and / or preventing an infectious disease of the oral cavity described herein comprises administering to a subject an effective amount of the strain Saccharomyces cerevisiae var boulardii number I-3799, or a combination of a yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with the inactivated dry form of the strain Saccharomyces cerevisiae (e.g. strain number I-3856). The effective amount, which may be administered in one or more doses, may be determined by the physician or dentist. The exact amount to be administered may vary from patient to patient, depending on the patient's age, weight, general condition, severity and / or extent of dental caries or periodontal disease, etc. The effective amount to be administered may also vary depending on the desired therapeutic effect (i.e., prevention of an infectious disease of the oral cavity or treatment of an infectious disease of the oral cavity).

[0052] Preferably, the administration of the strain Saccharomyces cerevisiae var boulardii number I-3799, or a combination of a yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with the inactivated dry form of the strain Saccharomyces cerevisiae (e.g. strain number I-3856), is an oral administration with an effect localized to the oral cavity, however in some embodiments the yeast (or combination) may be swallowed (see below).

[0053] For example, the dose of a yeast combination Saccharomyces cerevisiae var boulardii in dry form (e.g. strain number I-3799) and a yeast Saccharomyces cerevisiae in inactivated dry form (e.g. strain number I-3856) may be between 1 mg and 10 g, preferably between 100 mg and 5 g of the mixture.

[0054] The recommended concentration of yeast Saccharomyces cerevisiae var. boulardii live may be between 1·10 7< and 1.10 11< CFU / g, and preferably between 5.10 8< and 1·10 10< CFU / g.

[0055] A treatment method described herein may be used to treat a first episode of infectious disease of the oral cavity, particularly gingivitis or periodontitis, or a recurrence. In either case, the patient may have previously been treated with a standard antibiotic. Alternatively, yeast Saccharomyces cerevisiae var boulardii number I-3799, or the combination of a yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with a yeast of Saccharomyces cerevisiae (e.g. strain number I-3856), may be the first treatment prescribed to the patient.

[0056] A treatment method described herein may also be used to prevent an infectious disease of the oral cavity in a patient, whether the infectious disease of the oral cavity is a first episode or a recurrence. This may be the case for patients receiving medical treatment known to cause disturbances of the periodontium, such as immunosuppressants, phenytoin (anti-epileptic), calcium channel blockers such as nifedipine (which are indicated in the treatment of various cardiac disorders such as angina pectoris, arrhythmias, and high blood pressure). This may also be the case for patients suffering from immunovulnerability, for example, associated with a disease such as Sjögren's syndrome, HIV infection, uncontrolled diabetes, certain endocrine disorders, malnutrition or malabsorption such as, for example, vitamin B deficiency.This may also be the case for patients with reduced salivary flow (for example, some elderly people). This may also be the case for smokers or people in periods of stress. This may also be the case for pregnant women, for whom prevention of oral diseases can begin at the beginning of pregnancy. Finally, this may be the case for people with a hyper-inflammatory phenotype, i.e., those with a propensity to provoke an exacerbated inflammatory reaction by responding, when faced with an aggression of the same intensity, with an overproduction of pro-inflammatory cytokines (PGE2, IL-1, TNF), factors that play a major role in periodontal destruction.

[0057] In some embodiments, a treatment described herein is administered alone. In other words, the yeast Saccharomyces cerevisiae var boulardii number I-3799, or the combination of a yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with the inactivated dry form of a yeast Saccharomyces cerevisiae (e.g. strain number I-3856), is the only agent to be administered, with the exception of possible antiseptic mouthwashes.

[0058] In other embodiments, a treatment described herein is administered in combination with another therapy, for example with the administration of a conventional antibiotic or antiseptic, and / or with a mechanical or surgical procedure, such as scaling, root planing, curettage, filling, restoration, or root canal treatment. IV - Compléments Alimentaires, Compositions Cosmétiques et Pharmaceutiques

[0059] As stated above, the strain Saccharomyces cerevisiae var boulardii number I-3799, or the combination of a yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with the inactivated dry form of a strain Saccharomyces cerevisiae (e.g. strain number I-3856), may be administered as such or in the form of a preparation or composition.

[0060] Thus, in some embodiments, the strain Saccharomyces cerevisiae var boulardii number I-3799, or the combination of a yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with the inactivated dry form of a strain Saccharomyces cerevisiae ( for example strain number I-3856), is present in a food supplement in the form of a lozenge, a candy, a chewing gum, an orodispersible powder or to be diluted in water in the form of a stick or sachet, a tablet to be sucked or chewed, a chewing gum, a capsule, a tablet, drops, or a vial with a measuring cap, etc.

[0061] In other embodiments, the strain Saccharomyces cerevisiae var boulardii number I-3799, or the combination of a yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with the inactivated dry form of a strain Saccharomyces cerevisiae ( for example strain number I-3856), is present in a parapharmaceutical (or cosmetic) composition in the form of a toothpaste, a mouthwash, an oral spray, an oral cream or gel, an orodispersible sheet, or a powder that can be sprinkled directly into the oral cavity, an orodispersible powder or to be diluted in water in the form of a stick or sachet, a vial with a measuring cap, etc.

[0062] In still other embodiments, the strain Saccharomyces cerevisiae var boulardii number I-3799, or the combination of a yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with the inactivated dry form of a strain Saccharomyces cerevisiae ( for example strain number I-3856), is present in a pharmaceutical composition with at least one physiologically acceptable excipient. Thus, more specifically, a pharmaceutical composition according to the invention comprises an effective amount of the yeast strain Saccharomyces cerevisiae var boulardii number I-3799, or the combination of a yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with the inactivated dry form of a strain Saccharomyces cerevisiae ( for example strain number I-3856), and at least one physiologically acceptable excipient. A pharmaceutical composition according to the invention may be classified as a pharmaceutical preparation available on prescription or over the counter.

[0063] In the context of the present invention, "physiologically acceptable excipient" means any medium or additive which does not interfere with the effectiveness of the biological activity of the active ingredient (here the strain Saccharomyces cerevisiae var boulardii number I-3799 or the combination), and which is not excessively toxic to the patient or subject at the concentrations at which it is administered. A physiologically acceptable excipient may be an excipient suitable for administration to mammals, particularly humans.

[0064] The pharmaceutical compositions according to the present invention may be administered using any combination of dosage and route of administration effective to achieve the desired therapeutic / prophylactic effect. As already indicated above, the exact amount to be administered may vary from patient to patient, depending on the age, weight, general condition of the patient, the severity and extent of the oral infection and the nature of the associated oral disease (dental caries, gingivitis, periodontitis), etc. The route of administration (topical or systemic) may be chosen depending on the severity and extent of bacterial infection and / or the age and / or health of the patient.

[0065] By way of example, the subject of the invention is a pharmaceutical composition as defined above for use of a combination of yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) and the inactivated dry form of a yeast Saccharomyces cerevisiae (e.g. strain number I-3856) in an amount of between 1 mg and 10 g, preferably between 100 mg and 5 g, this amount being able to be administered once or several times a day.

[0066] The recommended concentration of yeast Saccharomyces cerevisiae var. boulardii may be between 1·10 7< and 1.10 11< CFU / g, and preferably between 5.10 8< and 1·10 10< CFU / g.

[0067] The formulation of a pharmaceutical composition according to the present invention may vary depending on the route of administration and the dosage for which the composition is intended to be used. After formulation with at least one physiologically acceptable excipient, a pharmaceutical composition of the invention may be in any form suitable for administration to a human being, for example in the form of tablets, pills, dragees, capsules, pearls, syrups, emulsions, ointments, pastes, gels, powders, sachets, injectable solutions, etc. Those skilled in the art know how to select the most appropriate vehicles and excipients for the preparation of a given type of formulation. A composition according to the invention may further comprise additives such as preservatives, sweeteners, flavorings, viscosifying agents, colorings, humectants, disintegrating agents, absorption accelerators, lubricating agents, etc.

[0068] In certain embodiments, a pharmaceutical composition according to the invention contains only one active agent: yeast Saccharomyces cerevisiae var boulardii number I-3799 or the combination of a yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with the inactivated dry form of a yeast Saccharomyces cerevisiae (e.g. strain number I-3856). Such a pharmaceutical composition does not contain, in particular, another live microorganism or a combination of live microorganisms.

[0069] In other embodiments, a pharmaceutical composition according to the invention further contains at least one additional pharmaceutical active ingredient (i.e., in addition to yeast Saccharomyces cerevisiae var boulardiiI-3799 or yeasts in the combination). "Active pharmaceutical ingredient" means any compound or substance whose administration has a therapeutic effect or whose administration has a beneficial effect on the health or general condition of a patient or subject to whom it is administered.

[0070] Thus, a pharmaceutical active ingredient may be active against a bacterial infection of the oral cavity that is to be prevented or treated by administering the pharmaceutical composition; or may be active against a condition or symptom associated with the infectious disease of the oral cavity (e.g., pain or fever or halitosis); or may increase the availability and / or activity of the active ingredient(s) of the pharmaceutical composition.

[0071] Examples of pharmaceutical active ingredients that may be present in a composition of the present invention include, without limitation, active ingredients having soothing, anti-irritant, analgesic, analgesic, anti-inflammatory, healing, antibiotic, antipyretic, or antifungal activity (without effect on yeast Saccharomyces cerevisiae var boulardii number I-3799 or on the combination of a yeast Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with a yeast Saccharomyces cerevisiae in inactivated dry form (e.g. strain number I-3856)), etc.

[0072] In still other embodiments, the strain Saccharomyces cerevisiae var boulardii number I-3799, or the combination of a souche Saccharomyces cerevisiae var boulardii (e.g. strain number I-3799) with the inactivated dry form of a strain Saccharomyces cerevisiae ( for example strain number I-3856), is present on / in a dental medical device: for example a dental implant, a dental crown, a dental bridge, a dental onlay, a dental prosthesis, etc.

[0073] Unless otherwise defined, all technical and scientific terms used in the Description have the same meaning as commonly understood by a person of ordinary skill in the art to which this invention pertains. Exemples

[0074] The following examples describe certain embodiments of the present invention. However, it is understood that the examples and figures are presented for illustrative purposes only and do not limit the scope of the invention in any way. Légende des Figures

[0075] Figure 1 : Halo results obtained (A) with the stump Saccharomyces cerevisiae number I-3856, in the presence of pathogenic species: Fusobacterium nucleatum (Fn), Prevotella intermedia (Pi), Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg) (B) with the stump Saccharomyces cerevisiae var boulardii number I-3799, in the presence of pathogenic species: Fusobacterium nucleatum (Fn), Prevotella intermedia (Pi), Aggregatibacter actinomycetemcomitans (Aa), and Porphyromonas gingivalis (Pg); (a) in aerobic or (b) anaerobically. Figure 2 : Effects of the strain Saccharomyces cerevisiae number I-3856 (I-3856); of the strain Saccharomyces cerevisiae var boulardii number I-3799 (Boulardii); and a control (Control) on different bacterial species of a 14-species biofilm, including 4 periodontopathogens (A has D), and 2 cariopathogens ( E And F ): (A) Aggregatibacter actinomycetemcomitans (Aa), (B) Fusobacterium nucleatum (Fn), (C) Porphyromonas gingivalis (Pg), (D) Prevotella intermedia (Pi), (E) Streptococcus mutans (Sm), (F) Streptococcus sobrinus. Values ​​represent mean ± SE from triplicates (N=3). *p<0.05 vs. Control; **p<0.01 vs. Control; ***p<0.001 vs. Control; **** p<0.0001 vs. Control. Figure 3 : Effects of the inactivated dry form of the strain Saccharomyces cerevisiae number I-3856 (IY)); of the strain Saccharomyces cerevisiae var boulardii number I-3799 (Boulardii); from the combination of the inactivated dry form of the strain Saccharomyces cerevisiae number I-3856 and the strain Saccharomyces cerevisiae var boulardii number I-3799 (IY+Boulardii); and a control (Control) on different bacterial species of a 14-species biofilm, including 4 periodontopathogens ( A has D ), and 2 cariopathogens ( E And F ): (A) Aggregatibacter actinomycetemcomitans (Aa), (B) Fusobacterium nucleatum (Fn), (C) Porphyromonas gingivalis (Pg), (D) Prevotella intermedia (Pi), (E) Streptococcus mutans (Sm), (F) Streptococcus sobrinus.Values ​​represent mean ± SE from triplicates (N=3). *p<0.05 vs. Control; **p<0.01 vs. Control; ***p<0.001 vs. Control; **** p<0.0001 vs. Control. # p<0.05 vs. Nutri. $ p<0.05 vs. Boulardii. Figure 4 : Dose-effect curves of yeast Saccharomyces cerevisiae var. boulardii CNCM I-3799 on the secretion of the following different inflammatory parameters: ( A ) IL-6, ( B ) IL-8, ( C ) IL-10, ( D ) MCP-1, ( E ) PGE-2, and ( F ) isoprostane, by human primary monocytes after LPS challenge. Values ​​are expressed as mean ± SE from duplicate experiments performed for three donors (n=6). *** p<0.001 vs. Control, **** p<0.0001 vs. Control. Figure 5 : Dose-effect curves of yeast Saccharomyces cerevisiae var. boulardii CNCM I-3799 on the secretion of the following different inflammatory parameters: ( A ) IL-6, ( B ) IL-8, (C ) PGE-2, and ( D ) isoprostane, by human primary gingival fibroblasts. Values ​​are expressed as mean ± SE for three experiments (n=3). *** p<0.001 vs. Control, **** p<0.0001 vs. Control. Effects of Different Probiotics on Periodontopathogenic Bacteria and Cariogenic Bacteria A. Tested Probiotics and Periodontopathogenic or Cariogenic Bacteria

[0076] Yeast Products. In the studies described below, 2 live dry yeasts, and one inactivated dry yeast were evaluated.

[0077] The two live yeasts are: The strain Saccharomyces cerevisiae CNCM number I-3856 (filed, by the Applicant, with the CNCM on October 17, 2007), and The strain Saccharomyces cerevisiae var boulardii CNCM number I-3799 (already described above).

[0078] Inactivated dry yeast is: The inactivated dry form of the strain Saccharomyces cerevisiae number I-3856 (already described above). Composition of a complex 14-species biofilm:

[0079] Periodontopathogenic Bacteria and Cariogenic Bacteria. Among the periodontopathogenic bacteria used are: Prevotella intermedia(formerly known as Bacteroides intermedius ) which is an obligate anaerobic, Gram-negative pathogenic bacterium involved in periodontal infections, including gingivitis and periodontitis, and often found in acute necrotizing ulcerative gingivitis; Porphyromonas gingivalis, which is an anaerobic, non-motile, Gram-negative, rod-shaped pathogenic bacterium found in the oral cavity, where it is implicated in certain forms of periodontal disease; Fusobacterium nucleatum, which is an anaerobic, invasive, adherent and inflammatory bacterium, foreign to the human oral cavity, and which plays a role in periodontal disease by being a key component of periodontal plaque due to its abundance and its ability to associate with other species in the oral cavity; and Aggregatibacter actinomycetemcomitans,which is a small, slow-growing, Gram-negative, facultative aerobic-anaerobic bacterium belonging to the physiological oral flora of humans, and playing a role in periodontal disease.

[0080] Among the cariogenic bacteria used are: Streptococcus mutans, which is a Gram-positive cocci bacterium, part of the commensal flora of the oral cavity where it is responsible for dental caries in combination with dietary sugar which it transforms into lactic acid; and Streptococcus sobrinus, which is a Gram-negative, non-motile, anaerobic bacterium, present in large quantities in the dental plaque of patients with caries.

[0081] Commensal Bacteria of the Oral Cavity. Among the oral cavity commensal bacteria used in the present study, we find: Streptococcus sanguinis ; Streptococcus gordonii ; Streptococcus salivarius, Streptococcus mitis ; Streptococcus oralis; Actinomyces viscosus ; Actinomyces naeslundii ; And Veillonella parvula. B. Antibacterial Activity of Yeasts against 6 Pathogenic Species

[0082] Protocol. The halo technique was used to detect and quantify the inhibition rate of commensal and pathogenic bacteria on agar plates. This technique is a competitive test, which consists of inoculating two spots, close to each other and each containing a different bacterial species, on an agar plate. Then, the ability of one to inhibit the growth of the other can be assessed.

[0083] The agar plates were inoculated with the culture of one of the 2 (live) yeasts adjusted to an optical density at 600 nm (OD 600 ) of 0.5, which corresponds to a concentration of approximately 10 8 < CFU / ml - the BHI-2 agar plates did not contain hemin, menadion or blood. Each spot contained 7 µL of the culture of one of the 2 live yeasts with a concentration of 10 8 < CFU / ml.

[0084] After 24 hours of aerobic or anaerobic incubation, the agar plates were again inoculated for 24 hours with 7 µl of a culture of a pathogenic species ( Fusobacterium nucleatum (Fn), Prevotella intermedia (Pi), Aggregatibacter actinomycetemcomitans (Aa), and Porphyromonas gingivalis (Pg), very close to the spot containing the yeast species.

[0085] In total, the agar plates were incubated for 48 hours either anaerobically or aerobically. After the 48-hour incubation, the inhibition surface was inspected and calibrated (with a ruler) (Table 1), and a standardized photograph (distance between the agar plate and the camera) was taken of each of the agar plates ( Figure 1 ).

[0086] The pathogens tested with the 2 live yeasts are as follows: Fusobacterium nucleatum (Fn), Prevotella intermedia (Pi), Aggregatibacter actinomycetemcomitans (Aa), and Porphyromonas gingivalis (Pg),

[0087] Results. The results obtained are presented on the Figure 1 and summarized in Table 1. Table 1. Inhibition rates (mean ± standard deviation, N =3) induced by the yeast species Saccharomyces cerevisiae var. boulardii I-3799 on the growth of certain oral pathogenic bacteria. Bacterial Competition mean inhibition distance ± SD* (mm) S. boulardii (24 h anaerobic) + P. intermedia (24 h anaerobic) 6,19 ± 0,09 S. boulardii (24 h anaerobic) + P. gingivalis (24 h anaerobic) 3,11 ± 0,14 S. boulardii (24 h anaerobic) + A. actinomycetemcomitans (24 h aerobic) 4,48 ± 0,14 S. boulardii (24 h aerobic) + A. actinomycetemcomitans (24 h aerobic) 0,52 ± 0,07 *SD = standard deviation

[0088] Table 1 provides the inhibition distances measured for cases where the growth of certain oral pathogens was significantly inhibited.

[0089] The results obtained show that the strain Saccharomyces cerevisiae var boulardii induces significant inhibition of the growth of pathogenic species Prevotella intermedia, Aggregatibacter actinomycetemcomitans, And Porphyromonas gingivalis under anaerobic conditions.

[0090] In addition, the growth of 'Aggregatibacter actinomycetemcomitans was also inhibited by the strain Saccharomyces cerevisiae var boulardii under aerobic conditions.

[0091] Table 1 shows that the greatest order of magnitude of inhibition was observed on the growth of Prevotella intermedia under anaerobic conditions compared to other bacteria and pathogens.

[0092] We also observe on the Figure 1 that the strain Saccharomyces cerevisiaeCNCM I-3856 showed no significant inhibition of pathogenic species.

[0093] Conclusion. Only the strain Saccharomyces cerevisiae var boulardii inhibited the growth of oral pathogens on agar plates. C. Evaluation of the Effect of Yeast Products on the Composition of a Complex Biofilm Comprising 14 Species. 1) Effects of Live Yeasts Studied

[0094] Bioreactor Protocol. A multi-species community was established in a BIOSTAT B TWIN ®< reactor (Sartorius, Germany). Medium containing 750 ml of BHI-2 (Brain Heart Infusion (BHI) supplemented with 2.5 g / l mucin, 1.0 g / l yeast extract, 0.1 g / l cysteine, 2.0 g / l sodium bicarbonate, and 0.25% (v / v) glutamic acid) was added to the bioreactor along with 5.0 mg / ml hemin, 1.0 mg / ml menadione, and 200 µl / l Antifoam Y-30 (Sigma, St. Louis, USA). The mixture was pre-reduced for 24 hours at 37°C by bubbling 100% nitrogen (N2) and 5% carbon dioxide (CO2) through the mixture while continuously stirring at 300 rpm, at a pH set at 6.7 ± 0.1. After 24 hours, the cultures of Streptococcus mutans (E), Streptococcus sobrinus (F), Prevotella intermedia (D), Porphyromonas gingivalis (C), Fusobacterium nucleatum (B), And Aggregatibacter actinomycetemcomitans (A) were added at an optical density of 1.4 and added to the bioreactor mixture. The medium was not replaced for the first 48 hours and was then replaced at a rate of 200 ml / 24 hours.

[0095] Cultures Protocol. The strain cultures Saccharomyces cerevisiae number I-3856 (I-3856) and the stub Saccharomyces cerevisiae var boulardii number I-3799 ( Boulardii) (performed overnight) were adjusted to an optical density at 600 nm (OD 600 ) of 0.5 (~1x10 8< CFU / ml) in BHI-2 (see composition above). Aliquots of 1800 µl of these adjusted cultures were inoculated onto 24-well plates containing hydroxyapatite discs at the bottom of each well. 200 µl of the 14-species biofilm mixture from the bioreactor was added to each well. Controls contained 200 µl of the 14-species samples and 1800 µl of BHI-2. The 24-well plates were incubated under microaerobic conditions (6% oxygen) for 24 hours. Then, the supernatants were removed and the biofilms attached to the hydroxyapatite discs were washed with PBS (phosphate buffered saline). The biofilms were detached with 1500 µl of 0.05% Trypsin-EDTA for 45 minutes at 37°C and 230 rpm, then transferred to Eppendorf tubes, and centrifuged (6010 xg, for 5 minutes).After trypsin removal, the biofilm pellet was resuspended in 500 µl of PBS, and DNA extraction was performed according to Qiagen instructions and analyzed by qPCR.

[0096] Results Obtained on Live Yeasts. The results obtained are presented on the Figure 2 (A- F).

[0097] It is observed that the strain Saccharomyces cerevisiae var boulardii is able to significantly inhibit the following periodontopathogens Aggregatibacter actinomycetemcomitans (A), Fusobacterium nucleatum (B), Porphyromonas gingivalis (C) and, Prevotella intermedia (D) as well as the cariopathogen Streptococcus mutans (E) .

[0098] Conclusion. Biofilm experiments confirmed, in multi-species communities, the inhibitory activity of the strain Saccharomyces cerevisiae var boulardii against oral pathogens, which had been demonstrated above in experiments on agar plates. 2) Effects of the Strain Saccharomyces cerevisiae var boulardii I-3799 (boulardii yeast), Inactivated Dry Form of the Strain Saccharomyces cerevisiae I-3856 (IY yeast), and their Combination

[0099] The yeast products (boulardii and IY) were each dissolved in 100 ml of PBS at 37°C and vortexed for 3 minutes. 10 ml of these solutions were centrifuged at 6010 xg for 10 minutes. The supernatants were removed and the pellet of the “Boulardii” yeast was suspended in BHI-2 by adjusting the concentration to an average of 5x10 8< CFU / ml. The pellet of the “IY” yeast was suspended in a solution containing a sample of the bioreactor mixture diluted 1:5. In a first well, were placed: 1 ml of the solution of the yeast "Boulardii" suspended in BHI-2 and 1 ml of the bioreactor mixture diluted 1 / 5 without "IY" (condition "Boulardii" alone) In a second well, were placed: 1 ml of the solution of the yeast "IY" and the bioreactor mixture diluted 1 / 5 and 1 ml of BHI-2 without "boulardii" (condition IY alone). In a third well, were placed: 1 ml of the solution of the yeast "Boulardii" suspended in BHI-2 and 1 ml of the solution of the yeast "IY" and the bioreactor mixture diluted 1 / 5 (condition combination Boulardii + IY). In a fourth well, were placed: 1 ml of the bioreactor mixture diluted 1 / 5 and 1 ml of BHI-2. This well constitutes a control well.

[0100] The 24-well plates were incubated under microaerobic conditions (6% oxygen) for 24 hours. Then, the supernatants were removed, and the biofilms attached to the hydroxyapatite discs were washed with PBS. The biofilms were detached with 1500 µL of 0.05% Trypsin-EDTA for 45 minutes at 37°C and 230 rpm, then transferred to Eppendorf tubes, and centrifuged (6010 xg, for 5 minutes). After trypsin removal, the biofilm pellet was resuspended in 500 µL of PBS, and DNA extraction was performed according to Qiagen's instructions and analyzed by qPCR.

[0101] Results. The results obtained are presented on the Figure 3 and in Table 2. Table 2. Difference between control values ​​and values ​​of biofilm pathogenic species (hereinafter δ) in the presence of the strain Saccharomyces cerevisiae var boulardii I-3799 (Boulardii), from the inactivated dry form of the strain Saccharomyces cerevisiae 1-3856 (IY), and their combination. Pathogenic species δ IY δ Boulardii Sum δ IY + δ Boulardii δ Combination IY + Boulardii Aa 0,46 0,38 0,84 1,1 Fn 0,65 0,59 1,24 1,47 Pg 0,32 0,2 0,52 0,77 Pi 0,3 0,6 0,9 1,38 Sm 0,51 0,43 0,94 1,4 NB: The values ​​presented in Table 2 are not absolute values. They correspond to the difference between the control values ​​and the pathogen values.

[0102] These results show that each of the two strains individually ( Saccharomyces cerevisiae var boulardii (Boulardii) and Saccharomyces cerevisiae inactivated (IY) and their combination are able to significantly inhibit the growth of two periodontal pathogens Aggregatibacter actinomycetemcomitans or Aa (A) and Fusobacterium nucleatum or Fn (B) and cariogenic bacteria Streptococcus mutans or Sm (E). Moreover, Table 2 shows that the δ of the combination IY + Boulardii is greater than the sum of the δ IY and δ Boulardii taken individually.

[0103] According to the Figure 3 (C) , the growth of Porphyromonas gingivalis or Pg(C) was inhibited by yeast Saccharomyces cerevisiae inactivated (IY) as well as by the combination but was not significantly so by the strain Saccharomyces cerevisiae var boulardii (Boulardii). In addition, a significant difference in inhibition can be observed between inactivated yeast (IY) and the Boulardii + IY combination, thus demonstrating a synergistic action of the combination on the inhibition of growth of Porphyromonas gingivalis (C), confirmed by Table 2.

[0104] According to the Figure 3 (D) , the growth of Prevotella intermedia or Pi (D) was inhibited by the strain Saccharomyces cerevisiae var boulardii as well as by the combination but was not significantly so by inactivated yeast (IY). Moreover, a significant difference in inhibition can be observed between the Boulardii strain and the Boulardii + IY combination, thus demonstrating a synergistic action of the combination on the inhibition of the growth of Prevotella intermedia (D), confirmed by Table 2.

[0105] Conclusion. Thus, it has been shown that the combination of the strain Saccharomyces cerevisiae var boulardii and the strain Saccharomyces cerevisiae inactivated, dry strain induced growth inhibition of most pathogens in the multi-species model used unlike the strain Saccharomyces cerevisiae var boulardii and yeast Saccharomyces cerevisiae inactivated individually taken which have a lower spectrum of inhibition of the growth of oral pathogens. Anti-inflammatory Effects of Saccharomyces cerevisiae var. boulardii I-3799

[0106] The aim of the study presented below is to evaluate the potential anti-inflammatory effects of yeast Saccharomyces cerevisiae var. boulardii CNCM I-3799 on inflammatory parameters of human primary monocytes and gingival fibroblasts. A. Evaluation of Anti-Inflammatory Potential on Human Primary Monocytes

[0107] Stimulation and Determination of Inflammatory Parameters in Human Primary Monocytes. Primary human monocytes were isolated and enriched from buffy coats of healthy human blood donors. Cells were seeded in 24-well plates (approximately 500,000 cells / ml in 1 ml) for ELISA experiments. Cells were incubated with LPS (10 ng / ml) for 24 hours. Yeast samples (5 doses ranging from 4.3 E< 6 CFU to 4.3 E< 8 CFU / ml, i.e.: 0.1 mg / ml; 1 mg / ml; 2.5 mg / ml; 5 mg / ml; 10 mg / ml) were added 30 minutes before LPS treatment directly into the cell culture. Dexamethasone was used as a positive control (2 doses, 1 µM and 10 µM). After 24 hours, supernatants were removed, centrifuged, and MCP-1, IL-8, IL-6, IL-10, isoprostane, and PGE2 concentrations were assessed. Concentrations in EIAs (PGE2 and isoprostane, from Cayman) or ELISAs (MCP-1, IL-6, and IL-8, from eBioscience) were assessed according to the manufacturer's protocols.Each dose was studied 6 times using buffy coats from 3 different donors (n=2 per buffy coat, n=6 in total).

[0108] Statistical Analysis. One-way ANOVA with Dunnett's multiple comparison tests at a significance level of 0.5.

[0109] Results. The results obtained are presented on the Figure 4 . These results show that the strain of Saccharomyces cerevisiae var boulardii CNCM I-3799 has a dose-dependent anti-inflammatory effect in human primary monocytes. Specifically, S. boulardii CNCM I-3799 is capable of inhibiting at a dose between 2.5 mg / ml (1 E< 8 CFU / ml) and 10 mg / ml (4.3 E< 8 CFU / ml) the secretion of IL-6, IL-10, MCP-1, PGE-2 and isoprostane while the cytokine IL-8 is inhibited at a minimum dose of 10 mg / ml (4.3 E< 8 CFU / ml). At low doses (from 0.1 to 1 mg / ml or from 4.3 E< 6 to 4.3 E< 7 CFU / ml), S. boulardiiCNCM I-3799 is able to stimulate the secretion of the anti-inflammatory cytokine Il-10 suggesting an immune-training effect. At higher doses, the inhibition of pro-inflammatory cytokines and PGE-2 / isoprostane markers indicate an anti-inflammatory effect and an inhibition of the prostaglandin pathway involved in the onset of pain and bone destruction. B. Evaluation of Anti-Inflammatory Potential on Human Primary Gingival Fibroblasts

[0110] Measurement of IL-8, IL-6, Isoprostane and PGE2 in Primary Human Gingival Fibroblasts. Human primary gingival fibroblast cultures supplied by Provitro (Berlin, Germany) were maintained according to the supplier's protocol. Before stimulation, cells were seeded in 24-well plates for ELISA experiments. Cells were incubated without (unstimulated control) or with IL-1β (10 U / ml) for 24 hours. Yeast samples were added 30 minutes before treatment with IL-1β in 5 doses (0.1 mg / ml; 1 mg / ml; 2.5 mg / ml; 5 mg / ml; 10 mg / ml) (n=3). Dexamethasone was used as a positive control (1 dose, 1 µM). After 24 hours, supernatants were collected, centrifuged, and IL-6, IL-8, isoprostane, and PGE2 concentrations were assessed by EIA (PGE2 and isoprostane, from Cayman) or ELISA (IL-6 and IL-8, from eBioscience) following the manufacturer's protocol. Each dose was studied at least 3 times.

[0111] Results. The results obtained are presented on the Figure 5. These results show that the strain of Saccharomyces cerevisiae var boulardii CNCM I-3799 has a dose-dependent anti-inflammatory effect in human primary gingival fibroblasts. Specifically, S. boulardii CNCM I-3799 is capable of inhibiting at a dose between 1 mg / ml (4.3 E< 7 CFU / ml) and 10 mg / ml (4.3 E< 8 CFU / ml) the secretion of IL-6, IL-8, PGE-2 and isoprostane. The inhibition of pro-inflammatory cytokines and PGE-2 / isoprostane markers indicate an anti-inflammatory effect and an inhibition of the prostaglandin pathway involved in the onset of pain and bone destruction.

Claims

1. Yeast strain of Saccharomyces cerevisiae var boulardii deposited on 21 August 2007 with the CNCM under number I-3799, or combination of said yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae, for use in the prevention and / or treatment of an infectious disease of the oral cavity in a subject, characterised in that the infectious disease is tooth decay, gingivitis or periodontitis.

2. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae, for use according to claim 1, characterised in that the Saccharomyces cerevisiae var boulardii yeast I-3799 or the yeast strain of Saccharomyces cerevisiae var boulardii of the combination is in the live dry form.

3. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to claim 1 or claim 2, characterised in that the yeast strain of Saccharomyces cerevisiae var boulardii of the combination is the strain deposited on 21 August 2007 with the CNCM under number I-3799.

4. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to any one of claims 1 to 3, characterised in that the yeast strain of Saccharomyces cerevisiae is the strain deposited on 17 October 2007 with the CNCM under number I-3856.

5. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to any one of claims 1 to 4, characterised in that the yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or the combination is comprised in a food supplement.

6. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to claim 5, characterised in that the food supplement is in the form of a pastille, a sweet, a chewing gum, an orodispersible powder or a powder to be diluted in water in the form of a stick or a sachet, a lozenge or chewable tablet, a chewing gum, a capsule, a tablet, drops, a vial with a measuring cap.

7. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to any one of claims 1 to 4, characterised in that the yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or the combination is comprised in a parapharmaceutical or cosmetic composition.

8. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to claim 7, characterised in that the parapharmaceutical or cosmetic composition is in the form of a toothpaste, a mouthwash, an oral spray, an oral cream or gel, an orodispersible sheet, a powder intended to be sprinkled directly into the oral cavity, an orodispersible powder or a powder to be diluted in water in the form of a stick or sachet, a vial with a measuring cap.

9. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to any one of claims 1 to 4, characterised in that the yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or the combination is comprised in a pharmaceutical composition, the pharmaceutical composition comprising an effective amount of the yeast strain of Saccharomyces cerevisiae var boulardii 1-3799, or the combination defined in any one of claims 1 to 4 and at least one physiologically acceptable excipient.

10. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to claim 9, characterised in that the pharmaceutical composition is intended for topical administration or for oral administration.

11. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to claim 9 or claim 10, characterised in that the pharmaceutical composition further comprises at least one additional pharmaceutical active ingredient having a soothing, anti-irritant, analgesic, anti-pain, anti-inflammatory, healing, antibiotic, antipyretic or antifungal effect.

12. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to any one of claims 1 to 4, characterised in that the yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or the combination is comprised in a dental medical device.

13. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to claim 12, characterised in that the dental medical device is a dental implant, a dental crown, a dental bridge, a dental onlay, or a dental prosthesis.

14. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to any one of claims 1 to 13, characterised in that the infectious disease of the oral cavity is caused by periodontopathogenic and / or cariopathogenic bacteria.

15. Yeast strain of Saccharomyces cerevisiae var boulardii I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to claim 14, characterised in that the periodontopathogenic bacteria are selected from Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, and / or the cariopathogenic bacteria is Streptococcus mutans.

16. Yeast strain of Saccharomyces cerevisiae var boulardii yeast strain I-3799 or combination of a yeast strain of Saccharomyces cerevisiae var boulardii with the inactivated dry form of a yeast strain of Saccharomyces cerevisiae for use according to any one of claims 1 to 15, characterised in that the infectious disease of the oral cavity is a side effect of a medical treatment, or in that the infectious disease of the oral cavity is present or likely to develop or recur in a patient suffering from immunovulnerability, or in that the subject is a pregnant woman, an elderly person, a child, or a patient with a hyperinflammatory phenotype.