FR3038839A1 - VICHY WATER TO MODULATE BACTERIAL GROWTH - Google Patents

Abstract

The invention belongs to the field of products for modulating microbial growth, preferably for inhibiting the growth of pathogenic microorganisms and / or stimulating the growth of non-pathogenic microorganisms, and / or stimulating the metabolism of microorganisms. The application relates more particularly to the use of Vichy water or compositions comprising it in these applications.

Description

The invention belongs to the field of products for modulating microbial growth, preferably for inhibiting the growth of pathogenic microorganisms and / or stimulating the growth of non-pathogenic microorganisms, and / or stimulate the metabolism of microorganisms. The application aims more particularly futilisation waters of the Vichy basin or compositions comprising them in these applications.

Micro-organisms are present everywhere in man's environment: both in his direct environment and within the human body itself. We call microbiota all of these living microorganisms in a specific environment. The human microbiota, also called microbial flora, is the set of microorganisms present on or in the human body (including the intestinal microbiota).

Most microorganisms in the microbiota are either harmless or even beneficial to the host. By way of example, lactic acid bacteria convert sugars into lactic acid in the intestines and thus participate in their proper functioning. It has been shown in particular that the balance of the intestinal microbiota is important for the proper functioning of the immune system, and would protect against the development of metabolic diseases.

However, the need to control the proliferation of pathogens, particularly pathogenic bacteria and yeasts, has led to the discovery of antibiotics, which are now widely used not only in medicine but also in a large number of products of everyday life.

The known antibiotics, however, have several disadvantages. On the one hand, they lead to the development of treatment-resistant microorganisms. On the other hand, their spectrum of action is broad, that is to say that they are not specific to a bacterium or a given family of bacteria, but act on a large number of them . As a result, therapeutic futilization of antibiotics disrupts the balance of microbial flora, hindering its protective effect. The long-term use of antibiotics is therefore difficult, as it weakens the patient, favoring future microbial infections.

These disadvantages can be partly compensated by the subsequent administration of probiotics and / or prebiotics, which make it possible to reconstitute a protective flora. This solution remains imperfect, however. Indeed, at present there are few bacterial strains available as probiotics, and moreover they represent only a small part of the flora destroyed by antibiotics.

There is therefore a need for alternative products that are more efficient and preferably less deleterious than the known antibiotics. In other words, the problem to be solved by the invention lies in the development of products or compositions having antimicrobial properties without the known disadvantages.

In the context of the invention, the Applicant has demonstrated previously unknown properties of Vichy waters in the modulation of microbial growth.

In particular, he determined that Vichy waters have both antibacterial and antifungal properties, and on the other hand facilitate the growth of certain microorganisms. In a particularly surprising way, Vichy waters have both an antibacterial and antifungal effect on pathogenic bacteria and fungi, and in addition, a stimulating effect on the growth of beneficial bacteria. These properties are particularly useful in therapeutic treatments, but also in uses simply to maintain the proper balance of the flora, for example intestinal flora.

In addition, the Applicant has established that Vichy waters are capable of stimulating the metabolism of certain microbes, and thus the production of products secreted by these microbes. This latter property naturally finds applications in the field of microorganism culture.

We already knew the anti-inflammatory, soothing, or draining properties of Vichy waters in humans. However, these properties all have in common an effect on the human body as such, that is to say on eukaryotic cells. Thus, there was nothing to indicate or suggest that the Vichy waters also have other properties, which affect micro-organisms. Indeed, this could not be deduced from existing knowledge, since microorganisms have a structure and a metabolism very different from human cells. These results are therefore very surprising.

The Applicant has further demonstrated that diluted or concentrated Vichy waters retain these properties, which can therefore be exploited in applications hitherto never contemplated, for example by using compositions comprising said Vichy waters at various concentrations. The invention therefore aims first and foremost the use of Vichy water or a composition comprising it for modulating microbial growth, preferably for inhibiting the growth of pathogenic microbes and / or stimulating the growth of non-pathogenic microbes, and / or stimulate the metabolism of microbes. In other words, the invention relates to Vichy water or a composition comprising it for modulating microbial growth, preferably for inhibiting the growth of pathogenic microorganisms and / or stimulating the growth of non-pathogenic microorganisms, and / or stimulate the metabolism of microorganisms.

For the purposes of the invention, the term "Vichy water" refers to water from one of the sources of the Vichy basin, such as for example the waters whose composition is given in Table 1, as well as their mixtures. Preferably, the terms "Vichy water" refer to Vichy water from the Chomel source, advantageously having the corresponding physicochemical composition in Table 1, Vichy water from the Lys source, advantageously having the composition Physico-chemical corresponding in Table 1, and Vichy water from the source Dome, preferably having the corresponding physicochemical composition in Table 1, and mixtures thereof.

Table 1: Chemical composition of Vichy waters The Vichy water according to the invention can be used either alone or in the compositions comprising it, in its natural form or reconstituted from salts, or in a diluted or concentrated form. In other words, Vichy water can be in a natural or reconstituted form, or in diluted or concentrated form. In addition, the compositions according to the invention may comprise Vichy water in the aforementioned forms.

The terms "natural Vichy water" or "Vichy water in a natural form" will more particularly be used to designate Vichy water which is neither diluted nor concentrated, nor has it undergone any transformation. The term "reconstituted Vichy water" will also be used to designate Vichy water obtained from the dissolution of salts obtained from the dehydration of Vichy water.

"Vichy water diluted" means a Vichy water whose saline composition is diluted in comparison with the saline concentration of natural Vichy water. By composition comprising diluted Vichy water it is meant that the saline composition of the Vichy water within the composition is diluted in comparison with the saline concentration of natural Vichy water. The dilution of the Vichy water may alternatively be characterized by the dilution factor, which corresponds to the ratio of the saline concentration of the natural Vichy water to the saline concentration of the water used, or to the composition comprising it. When the composition according to the invention comprises diluted Vichy water, it is preferably present in the composition at a saline concentration of between 0.5 and 0.8 times the saline concentration of natural Vichy water. preferably 0.625 times. In other words, when the composition according to the invention comprises diluted Vichy water, it is preferably diluted by a dilution factor of between 1.25 and 2, preferably diluted by a factor of dilution of 1.6, compared to natural Vichy water.

By "concentrated Vichy water" is meant a Vichy water whose saline composition is concentrated in comparison with the saline concentration of natural Vichy water. By composition comprising concentrated Vichy water is meant that the saline composition of Vichy water within the composition is concentrated in comparison with the saline concentration of natural Vichy water. When the composition according to the invention comprises concentrated Vichy water, it is preferably present in the composition at a salt concentration of at least 1.25 times, twice, 2.5 times, 5 times the saline concentration of natural Vichy water.

Within the meaning of the invention, it is possible to use gingham water or compositions comprising only part of Vichy water. Thus, preferably, the composition according to the invention comprises at least 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% d Vichy water, by weight relative to the weight of the composition.

The remarkable properties of Vichy waters make it possible to use them in different types of applications, in order to modulate microbial growth, in particular as a replacement for or in combination with known antibiotics, antifungals, or probiotics and prebiotics.

According to a first embodiment, the compositions comprising Vichy water of the invention are for use in the therapeutic treatment of bacterial or fungal infections.

The Applicant has notably demonstrated that Vichy water has very effective antimicrobial effects on the bacteria of the genera Staphylococcus and Pseudomonas, in particular Staphylococcus aureus and Pseudomonas aeruginosa, as well as antifungal properties on the yeasts of the genera Candida and Saccharomyces, in particular Candida albicans and Saccharomyces cerevisiae. The compositions of the invention can therefore advantageously be used in therapeutic treatments for infections due to these microorganisms, whether they are preventive or curative treatments.

Advantageously, the bacterial infection is a staphylococcal infection, preferably Staphylococcus aureus. Within the meaning of the invention, the term "staphylococcal infection" means any infection in which at least one microorganism of the genus Staphylococcus is superabundant, in comparison with reference abundance or with the abundance of the microorganism in the tissues. adjacent healthy. Those skilled in the art will readily be able to determine whether an infection is said to be "staphylococcal" according to well-known routine bioassays. Particularly preferably, the staph infection is selected from the group consisting of furuncles, paronychia, folliculitis, sycosis, impetigo, mastitis, acute myositis, osteomyelitis, pneumonia.

Advantageously, the bacterial infection is an infection with Pseudomonas, preferably Pseudomonas aeruginosa. For the purposes of the invention, the term "Pseudomonas infection" means any infection in which at least one microorganism of the genus Pseudomonas is superabundant, in comparison with a reference abundance or with the abundance of the microorganism in the tissues. adjacent healthy. Those skilled in the art can easily determine whether an infection is called "Pseudomonas" according to well-known routine biological tests. Particularly preferably, the Pseudomonas infection is selected from the group consisting of eye infections, urinary tract infections, genital infections, gastrointestinal infections, lung infections.

Advantageously, the fungal infection is a Candida infection, preferably Candida albicans. For the purposes of the invention, the term "Candida infection" means any infection in which at least one microorganism of the genus Candida is superabundant, in comparison with reference abundance or with the abundance of the microorganism in the tissues. adjacent healthy. Those skilled in the art can easily determine whether an infection is called "Candida" according to well-known routine biological tests. In a particularly preferred manner, the Candida infection is chosen from the group comprising cutaneomucous candidiasis, in particular the oral, genital, oropharyngeal or oesophageal candidiasis.

Advantageously, the fungal infection is a Saccharomyces infection, preferably Saccharomyces cerevisiae. Within the meaning of the invention, the term "Saccharomyces infection" refers to any infection in which at least one microorganism of the genus Saccharomyces is superabundant, in comparison with a reference abundance or with the abundance of the microorganism in the tissues. adjacent healthy. Those skilled in the art will readily be able to determine whether an infection is said to be "Saccharomyces" according to well-known routine bioassays. Particularly preferably, the Saccharomyces infection is selected from the group consisting of onyxis, genital infections, pulmonary infections.

In another embodiment, the invention is directed to compositions comprising Vichy water for use in stimulating the growth of beneficial bacteria.

For the purposes of the invention, the term "beneficial bacteria" refers to bacteria known for their beneficial effect on human health.

Bacillus subtilis, which can produce large amounts of digestive enzymes in the intestine such as alkaline protease, neutral protease, beta-glucanase and alpha-amylase, to facilitate the digestion of proteins, barley, glucan and starch in foods. Other well-known beneficial bacteria are lactic acid bacteria, such as, for example, bacteria of the genus Lactobacillus and bacteria of the genus Bifidobacterium.

The Applicant has notably demonstrated that Vichy water has positive effects on the growth of beneficial bacteria, in particular bacteria of the genus Lactobacillus.

Preferably, the beneficial bacteria are of the genus Lactobacillus, and are chosen from the group comprising the bacteria Lactobacillus acidophilus, L. amylovorus, L. casei, L. crispatus, L. delbruckii subsp. bulgaricus, L. gallinarum, L. gasseri, L. johnsonii, L. paracasei, L. plantarum, L. reuteri and L. rhamnosus, more preferably Lactobacillus acidophilus.

The stimulation of the growth of beneficial bacteria can be useful in the context of the treatment of a subject whose microbiotic flora, also called microbiota, is unbalanced. It has been shown that people with an unbalanced gut microbiota are more likely to develop gastrointestinal infections but also inflammatory bowel diseases, as well as metabolic diseases, such as obesity or diabetes.

In this perspective, the intended use can be considered as therapeutic, whether preventive or curative treatment. The compositions according to the invention will preferably be used to treat pathologies against which the administration of beneficial bacteria has proved useful, in replacement of probiotics or of conventional prebiotics, or in combination with them.

Preferably, compositions comprising Vichy water of the invention, which stimulate the growth of beneficial bacteria, are used for the treatment or prevention of lactose intolerance, diarrhea, peptic ulcers. , Crohn's disease.

The stimulation of the growth of beneficial bacteria can also be considered in the healthy subject, for the sole purpose of maintaining a commensal or beneficial microbial flora. In this case, the application can be considered as non-therapeutic, simply allowing a better-being. Indeed, healthy people will not get any therapeutic benefit from the treatment. The invention therefore further relates to the non-therapeutic use of Vichy water or composition comprising it, for maintaining or maintaining the microbial flora, preferably the intestinal or vaginal microbial flora, advantageously for a healthy subject.

By "healthy subject" or "healthy subject" is meant those subjects manifestly free of known pathologies, in other words in whom no pathology is manifested by symptoms known to the medical community. Preferably, the healthy subject or subject in good health does not have lactose intolerance, diarrhea, peptic ulcer, nor is affected by Crohn's disease.

This non-therapeutic use is distinguished from the use of Vichy waters for their digestive properties, whose mechanism is to buffer, thanks to the rich composition of bicarbonates in these waters, the gastric acidities responsible for hyposthenic dyspepsia (commonly referred to as "difficult digestion"). "). The use of Vichy waters to facilitate digestion is quickly assessed after ingestion of these waters, because it is based on a purely chemical mechanism. The use of Vichy waters to maintain or maintain the microbial flora probably proceeds from another mechanism, although this one is not known, because it tends to be observed after several days of use of the Vichy waters. Thus, preferably, the use of Vichy waters to maintain or maintain the microbial flora is repeated over time, particularly preferably is repeated for at least 48 consecutive hours. Said use can be carried out by consuming the composition according to the invention at regular intervals, this setting being spaced for example every 12 or 24 hours. The Vichy water or the composition according to the invention may be administered by any route of interest, preferably administered orally or rectally, and more preferably orally. The composition may be formulated in a manner suitable for the intended administration, for example in the form of a gel, a cream, a lotion, an emulsion (oil in water or water in oil ), a serum, a dispersion of lipid vesicles, tablets, capsules, granules, a liquid, a paste, capsules, suppositories, tampons or gynecological ova.

Advantageously, the composition according to the invention is in a form suitable for oral intake, in the form of a product or a liquid or solid food supplement, or in the form of tablets, capsules, granules.

The composition may further comprise one or more other active ingredients such as for example micronutrients, antibacterial agents, antifungal agents, prebiotics or probiotics.

The composition according to the invention may contain one or more other constituents chosen from excipients which are customary in pharmacy or in cosmetics, such as, for example, humectants, gelling agents, preservatives, filters, moisturizing agents, surfactants, emulsifiers, complexing agents, neutralizing agents and perfumes.

In addition, the Applicant has demonstrated that, in addition to the positive effect on the growth of lactic acid bacteria already described, Vichy waters also have an effect on the metabolism of certain bacteria, in particular cyanobacteria. Cyanobacteria, formerly known as blue-green algae, are known to synthesize, in their culture medium, compounds with antibacterial properties against bacteria involved in acne (acne vulgaris), Propionibacterium acnes and Staphyloccocus epidermidis. For this reason in particular, application FR 2 977 799 describes the use of culture medium of these cyanobacteria used in the preparation of antibacterial agents used for the prevention and treatment of skin infections.

The Applicant has demonstrated that the addition of Vichy water to the culture medium of these cyanobacteria has the effect of increasing the antibacterial properties of the culture medium resulting from said culture, also called enriched culture medium. Indeed, the Applicant has observed an antibiotic effect of this enriched culture medium on the growth of the bacterium Staphyloccocus aureus, which is also sometimes involved in acne vulgaris. The use of Vichy water in the culture of microorganisms, in particular cyanobacteria, is therefore of particular interest.

Among cyanobacteria, the cyanophycea class is preferred. Within this class, a micro-alga of the order Nostocales, in particular of the family of

Nostocaceae, and even more advantageously of the genus Nostoc, is advantageously chosen.

Thus, the invention aims at the use of Vichy water to stimulate the metabolism of microorganisms, preferably of the order of the Nostocales, in particular of the family Nostocaceae, and even more advantageously of the genus Nostoc. Preferably, the invention relates to the use of Vichy water in the culture of microorganisms, preferably of the order of Nostocales, in particular of the family of Nostocaceae, and even more advantageously of the genus Nostoc. The invention also relates to the methods of culturing bacteria in which the culture medium comprises Vichy water, as well as the product that can be obtained by this process, including in particular the culture medium obtained by this process and the extracts obtained from this culture medium.

According to one embodiment, the invention relates to a process for culturing a microorganism in which the culture medium comprises Vichy water, preferably comprises from 5% to 15%, more preferably 10% of water of Vichy in the culture medium, in volume relative to the volume of the culture medium, wherein the microorganism is preferably of the order of Nostocales, in particular of the family of Nostocaceae, and even more preferably of the genus Nostoc.

Preferably, the Vichy water used is Vichy water from the Chomel source or a water advantageously having the corresponding physicochemical composition in Table 1, the Vichy water from the Lys source or a water advantageously having the corresponding physicochemical composition in Table 1.

In addition, the invention relates to the enriched culture medium obtainable by the method of the invention. By "enriched culture medium" is meant in the sense of demand the culture medium obtained at the end of the culture process. Unlike the culture medium prepared for culturing the microorganism, the enriched culture medium comprises molecules excreted by the cultured microorganisms.

This enriched culture medium may be more particularly obtained by a process which advantageously comprises the following steps: a) culture of microorganisms, preferably of the order of Nostocales, in particular of the family Nostocaceae, and even more advantageously of the genus N os toc, in a culture medium comprising Vichy water; b) separation of microorganisms and enriched culture medium; c) recovering the enriched culture medium to obtain the extract.

Preferably, the culture medium is a culture medium adapted to the microorganism. A suitable medium for the culture of a cyanobacterium is advantageously a BG11 medium, also referenced ATCC Medium 616. The following media are also suitable: ATCC Medium 617 or BG-11 for Marine Blue-Green Algae: corresponds to an ATCC Medium 616 medium modified; ATCC Medium 819 or Blue-green Nitrogen-fixing Medium: corresponds to medium ATCC Medium 616 without N03.

BG11 medium is well known and has been described in particular in application FR 2 977 799. Its preparation and, where appropriate, its sterilization prior to use in the context of the process of the invention are well known to humans. of career.

The culture is carried out according to the usual conditions favorable to the growth of cyanobacteria, and well described in application FR 2 977 799. The duration of the culture of the microorganism may vary from several days to several weeks, or even several months. It is advantageously conducted from 21 days (3 weeks) to 55 days (8 weeks). At the end of the culture process, the microorganism can be separated from the enriched culture medium by any known method for ensuring the decantation of cyanobacteria, without affecting their structure, preferably by centrifugation. The enriched culture medium according to the invention is then recovered, for example by transfer or aspiration. It can advantageously be filtered, concentrated, purified or freeze-dried.

The enriched culture medium according to the invention can be used in the prevention and treatment of infections induced by Staphylococcus aureiis, Propionibacterium acnes and

Staphyloccocus epidermidis, such as, for example, skin infections or dermatoses having a bacterial component, in particular acne. For these therapeutic applications, the enriched culture medium is advantageously administered topically. It can therefore be formulated in a manner suitable for this administration, for example be incorporated into compositions whose formulation is preferably adapted to this administration, advantageously from 0.1 to 10% by weight of the composition, even more advantageously from 0.5 to 10%. It can then be mixed with conventional excipients acceptable in cosmetics or pharmacy. The compositions comprising the enriched culture medium according to the invention may also contain one or more other active substances, in addition to the extract described above. By way of example, a known anti-acne agent such as adapalene can be combined. Antibacterial agents such as benzoyl peroxide, erythromycin, or clindamycin can also be used in combination. The invention and the advantages thereof will emerge from the examples which follow, in support of the appended figures. These, however, have no limiting scope.

Examples of realization

Figures 1, 3 and 5: growth kinetics of L. acidophilus compared in the absence of Vichy water (curves shown in dotted lines) and in the presence of 10% Vichy water (curves shown in solid lines; source Chomel, figure 3: source of the Dome, figure 5 source of Lys). The curves illustrate the evolution of the value of the absorbance measured at 595 nm in time, which directly reflects cell proliferation.

Figures 2, 4 and 6 are graphs showing the percentage growth of L. acidophilus in the presence of 10% Vichy water (curves shown in solid lines, Figure 2: Chomel source, Figure 4: source of the Dome, Figure 6: Lys source) compared to the control containing no Vichy water (curves shown in dashed lines). The measurements are expressed as a percentage of growth relative to the control (100%). A value less than 100 means that there are fewer bacteria than in the control. On the other hand, a value greater than 100 means that the bacteria are more numerous than in the control. 1 / Use of Vichy water to inhibit the growth of pathogenic bacteria and fungi without destroying non-pathogenic bacteria:

The tests were conducted with Vichy water from three different thermal springs in the Vichy basin: the Chomel spring, the source of the Lily and the source of the Dome.

Several samples containing these Vichy waters are prepared at different concentrations, by evaporation. The waters of Vichy are reduced to the state of salts then reconstituted. Successive dilutions of Vichy water samples are obtained at the following concentrations: 5X, 2.5X, f, 25X, 0.625X.

TS culture media are prepared from these dilutions and then seeded with 100,000 bacteria per milliliter of the genus Staphylococcus aureus, or the genus Pseudomonas aeruginosa.

MRS culture media are also prepared from these dilutions and then inoculated with 100,000 bacteria per milliliter of the genus Latobacillus acidophilus.

Sabouraud culture media are also prepared from these dilutions, then seeded with 100,000 bacteria per milliliter of the genus Sacharomyces cerevisiae, or of the genus Candida albicans.

The cultures thus prepared are incubated at 37 ° C. for the bacteria or at 30 ° C. for the yeasts (Sacharomyces cerevisiae and Candida albicans). The antibacterial or antifungal activity is estimated visually after either 16 to 24 hours of culture (for bacteria) or 48 hours of culture (for yeasts).

Their culture medium is considered to have no antibacterial or antifungal activity when the cultures observed are turbid.

In contrast, when the cultures are clear (identical to the control medium without microorganism), it is considered that their culture medium has antibacterial or antifungal activity.

The minimum inhibited MIC concentration is the lowest tested concentration for obtaining antibacterial or antifungal activity, i.e., the lowest tested concentration with which the resulting culture is clear.

The results obtained are grouped in the following table:

It is found that all Vichy waters from the sources tested exhibit antibacterial activity against Staphylococcus aureus from a concentration corresponding to five times that of natural Vichy water (5X), and against Pseudomonas aeruginosa from a concentration corresponding to 2.5 times that of natural Vichy water (2.5X).

The Vichy waters tested also show antifungal activity against Saccharomyces cerevisiae and against Candida albicans from concentrations corresponding respectively to 0.625 times that of natural Vichy water (0.625X) and to 1.25 times that of groundwater. Natural gingham (1,25X).

On the other hand, these waters of the thermal springs of the Vichy Basin have no antibacterial effect on the non-pathogenic bacterium Lactobacillus acidophilus which remains preserved and develops with all the concentrations tested and thus up to a concentration corresponding to five times that of the natural Vichy water. The growth inhibitory effect of pathogenic bacteria and fungi in Vichy water, while preserving the survival of non-pathogenic bacteria, has been demonstrated. 2 / Use of Vichy water to stimulate the growth and / or increase the survival of beneficial bacteria:

Bacteria of the species Lactobacillus acidophilus at a concentration of 105 cfu / mL (colony-forming units per milliliter) were placed in anaerobic atmosphere in an MRS medium with or without 10% Vichy water. Three different Vichy water sources were tested: the Chomel spring, the source of the Lys and the source of the Dome.

The growth of the bacteria is measured in the various media tested maintained at 37 ° C. The growth of these bacteria was measured by absorbance of the optical density at 595 nm for 48 hours, using a Fluostar ™ measuring automaton (BMG Labtech) that measures every hour.

Figures 1 to 6 illustrate the results obtained.

It can be seen that regardless of the source of the Vichy water (Chomel source, Dôme or Lys) added at a level of 10% in the culture medium of the model bacterium Lactobacillus acidophilus, the addition of this water allowed a prolonged survival of the bacteria after a period of 15 to 26 hours, and thus had a protective effect of survival of these non-pathogenic, beneficial bacteria. 3 / Use of Vichy Water to Improve the Antibacterial Activity of Non-Pathogenic Bacteria The antibacterial activity of the cyanobacterial culture supernatant of the Nostoc type has been demonstrated in the patent application FR 2 77 799. The efficacy antibacterial substances released by these bacteria into their culture medium had been tested following a procedure described in this prior patent.

The same procedure was followed to carry out the present test, in order to determine whether the addition of Vichy water in the culture medium of this cyanobacterium of the Nostoc type has an influence on the antibacterial activity of the supernatant obtained, in particular on

Staphylococcus aureus.

A preculture of the cyanobacterial strain described in the patent application FR 2 977 799 is carried out in small volume (10 ml) in BG11 medium. As already described in the patent application FR 2 977 799, the cyanobacteria strain used was previously selected for its antibacterial activity against Staphylococcus epidermidis and against Staphylococcus aureus.

The medium BG11 can be of commercial origin (Sigma) or be reconstituted as follows:

with for the solution of metal salts, the following composition:

The pH was adjusted to 7.1, then autoclaved for 20 minutes at 121 ° C.

The bacteria are cultured in culture medium comprising 10% (volume / volume) of Vichy water in addition to fresh BG11 medium. Three different sources were tested: the source Chomel, the source of the Lily or the source of the Dome.

After 5-7 weeks of culture, the enriched culture medium was removed and the tubes in which the cyanobacteria were cultured were centrifuged.

The antibacterial properties of the enriched culture medium removed are evaluated on Staphylococcus aureus.

The enriched culture media are added to TS liquid medium containing 100,000 bacteria of the genus Staphylococcus aureus per milliliter.

The cultures are incubated at 37 ° C. under aerobic conditions for 16 to 18 hours and then observed visually. The turbid cultures are considered to contain an enriched culture medium that does not exhibit antibacterial activity against Staphylococcus aureus. The clear cultures (and thus identical to the initial medium) were considered to contain an enriched culture medium which exhibits antibacterial activity against Staphylococcus aureus.

The minimum inhibitory concentration (MIC) data of the culture media as described in Patent FR 2 997 799 B1, supplemented with 10% Vichy water originating alternately from the Chomel source, the Lys or the Dome, have been grouped together in the table below.

It is found that the enriched medium obtained from a culture medium in which 10% Vichy water from the Dome source was added does not inhibit the growth of Staphylococcus aureus.

In contrast, the enriched medium obtained from a culture medium in which 10% Vichy water from the Chomel source was added inhibits the growth of Staphylococcus aureus at a concentration of 3.125% (v / v). It is deduced that the minimum inhibitory concentration of this enriched medium is 3.125% (volume / volume), for Staphylococcus aureus.

In addition, the enriched medium obtained from a culture medium in which 10% of Vichy water from the Lys source has been added inhibits the growth of Staphylococcus aureus at a concentration of 12.5% (volume / volume). ). It is deduced that the minimum inhibitory concentration of this enriched medium is 12.5% (volume / volume), for Staphylococcus aureus.

It can therefore be concluded that Vichy water, in particular from the Chomel source or from the Lys source, increases the antimicrobial activity in the extracts produced according to the patent application FR 2 997 799.

Claims (10)

1. Vichy water for its use for modulating microbial growth, preferably for inhibiting the growth of pathogenic microorganisms and / or stimulating the growth of non-pathogenic microorganisms, and / or stimulating the metabolism of microorganisms, where Vichy water is selected from the group comprising Vichy water from the Chomel source having the corresponding physicochemical composition in Table 1, Vichy skin from the Lys source having the corresponding physicochemical composition in the Table 1, and Vichy water from the Dome source having the corresponding physicochemical composition in Table 1, as well as mixtures thereof. 2. Vichy water for use according to claim 1, characterized in that said Vichy water is used in a natural, diluted, concentrated or reconstituted form. 3. Vichy water for use according to claim 1 or 2, characterized in that the use is for the treatment of bacterial or fungal infections. 4. Vichy water for use according to claim 3, characterized in that the bacterial infection is a staphylococcal infection, preferably Staphylococcus aureus, more preferably selected from the group consisting of boils, paronychia, folliculitis, sycosis , impetigo, mastitis, acute myositis, osteomyelitis, pneumonia. 5. Vichy water for use according to claim 3, characterized in that the bacterial infection is a Pseudomonas infection, preferably Pseudomonas aeruginosa, more preferably selected from the group consisting of eye infections, urinary tract infections, genital infections , gastrointestinal infections, lung infections. 6. Vichy water for its use according to claim 3, characterized in that the fungal infection is a Candida infection, preferably Ccmdida albicans, more preferably selected from the group comprising mucocutaneous candidiasis, in particular oral, oropharyngeal or esophageal candidiasis . 7. Vichy water for use according to claim 3, characterized in that the fungal infection is a Saccharomyces infection, preferably Saccharomyces cerevisiae, more preferably selected from the group comprising onyxis, genital infections, pulmonary infections. 8. Vichy water for use according to claim 1, characterized in that the use is to stimulate the growth or increase the viability of beneficial bacteria, preferably of the genus Lactobacillus, more preferably Lactobacillus acidophilus. 9. Vichy water for use according to one of claims 4 to 8, characterized in that said composition comprises at least 10% by weight of said Vichy water. 10. Use of Vichy water in the culture of microorganisms, preferably of the order Nostocales, in particular of the family Nostocaceae, and even more advantageously of the genus Nostoc, where Vichy water is selected in the group comprising Vichy water from the Chomel source having the corresponding physicochemical composition in Table 1, Vichy water from the Lys source having the corresponding physicochemical composition in Table 1, and water Vichy from the Dome source having the corresponding physicochemical composition in Table 1, and mixtures thereof.