New composition for use as a food supplement and uses.

Abstract

New composition for use as a food supplement and uses. The invention relates to a new oral or sublingual composition comprising an extract of the microalga Tetradesmus sp. and / or an extract of the microalga Pavlova sp. The composition is used as a medicament, in particular for reducing intestinal hyperpermeability, and / or strengthening the intestinal barrier, and / or improving intestinal transit, and / or improving gastrointestinal disorders, and / or maintaining and / or increasing immune defenses and / or reducing stress. The composition improves well-being, sleep and cognitive abilities, particularly in humans.

Description

Title of the invention: New composition for use as a food supplement and uses. Technical field

[0001] The invention relates to an oral or sublingual composition comprising an extract of the microalga Tetradesmus sp. and / or an extract of the microalga Pavlova sp. Prior art

[0002] Intestinal dysbiosis is often cited as a major cause of intestinal hyperpermeability. While it is true that a change in the intestinal microbiota is often the cause, intestinal hyperpermeability can also be caused by an unbalanced diet, stress, environmental factors such as pollution, tobacco, but also allergies or intolerance such as gluten intolerance, milk protein intolerance or diseases such as celiac disease. Intensive sport can also be the cause of intestinal hyperpermeability. Intestinal hyperpermeability results in particular in gastrointestinal disorders such as diarrhea, bloating, abdominal pain and more generally in inflammation of the colon, which generates intestinal discomfort for those suffering from it.Whether or not it is associated with a lack of colon motility affecting intestinal transit, intestinal hyperpermeability plays a harmful role in overall health by also impacting well-being, stress, mood, but also sleep and cognition.

[0003] The field of nutraceuticals presents numerous solutions for modulating the intestinal microbiota, starting with the use of probiotics with the objective of regulating intestinal health, in particular by reducing intestinal hyperpermeability. However, the use of probiotics can cause gastrointestinal disorders, bloating, as well as acne or redness on the skin of consumers. There is therefore a need for alternative ingredients targeting intestinal hyperpermeability that do not have the disadvantages previously mentioned.

[0004] Surprisingly, the Applicant discovered that a composition comprising an extract of the microalga Tetradesmus sp. and / or an extract of the microalga Pavlova sp. had the capacity to reduce intestinal hyperpermeability, facilitate intestinal transit, prevent and / or reduce gastrointestinal disorders but also maintain and / or increase immune defenses.

[0005] The composition of the invention has the advantage of being natural, of being produced from a natural microalgae extract obtained from a bio-sourced solvent, and this from a microalgae cultivated under controlled conditions in a photobioreactor, easily industrializable.

[0006] Microalgae of the genus Tetradesmus belonging to the Scenedesmaceae family include more than a dozen distinct species. Among them is the species Tetradesmus obliquas. The species T. obliquus has two distinct morphotypes. It is also called Scenedesmus obliquus

[0007] The genus Pavlova is a genus of microalgae belonging to the Pavlovaceae family. Several species including P. pinguis, P. gyrans and P. lutheri are known. The species P. gyrans in particular is a microalgae of marine origin found in the Atlantic Ocean.

[0008] Application KR20170021958 describes a cosmetic composition comprising an extract of the microalgae Scenedesmus sp. in particular to promote cell growth, collagen synthesis, increase skin elasticity and improve pigmentation. In one embodiment, it is an extract of the strain S. obliquus. This composition is not suitable for topical use, and it is not possible to use it orally.

[0009] On the other hand, application CN112807337A1 discloses a composition which may comprise an extract of Scenedesmus for its use as a medicament, topically or orally, but no particular species is disclosed. In particular, the species Tetradesmus obliquus is not described or suggested.

[0010] Furthermore, no oral or sublingual composition comprising an extract of Pavlova sp. other than a peptide derived from a biomass of Pavlova lutheri fermented in the presence of the yeast Hanseluna polymorpha described in application KR20140088403 has ever been described.

[0011] Thus, to the knowledge of the Applicant, no composition comprising an extract of Tetradesmus sp., advantageously T. obliquus and / or an extract of Pavlova sp., advantageously P. gyrans and suitable for oral or sublingual use has been described. Statement of the invention

[0012] An object of the invention relates to an oral or sublingual composition comprising an extract of Tetradesmus sp., advantageously of T. obliquus and / or an extract of Pavlova sp., advantageously of P. gyrans, and at least one nutraceutically acceptable excipient.

[0013] Another subject of the invention relates to said composition or an extract of Tetradesmus sp., advantageously T. obliquus, and / or an extract of Pavlova sp., advantageously P. gyrans, for its use in reducing intestinal hyperpermeability and / or strengthening the intestinal barrier and / or improving intestinal transit; and / or in preventing and / or improving gastrointestinal disorders; and / or maintaining and / or increase immune defenses; and / or to reduce stress, advantageously stress induced by intestinal discomfort and / or chronic stress generating intestinal discomfort, in particular making it possible to improve intestinal well-being, sleep and / or cognitive abilities.

[0014] The invention therefore relates in the first instance to an oral or sublingual composition comprising an extract of Tetradesmus sp., advantageously of T. obliquas, and / or an extract of Pavlova sp., advantageously P. gyrans, and at least one nutraceutically acceptable excipient.

[0015] In one embodiment of the invention, the oral or sublingual composition is in the form of a food supplement, the term "food supplement" meaning indifferently a food supplement, a nutritional supplement, a dietary supplement, an over-the-counter supplement, a dietary supplement or a nutritional supplement.

[0016] EXTRACT

[0017] For the purposes of the present invention, the expression "extract of Tetradesmus sp." or "extract of Pavlova sp." is understood to mean any extract obtained by any extraction method known to those skilled in the art from any biomass of the microalga Tetradesmus sp., advantageously T. obliquus, or any biomass of the microalga Pavlova sp., advantageously P. gyrans. Advantageously, the biomass of Pavlova sp. has not been placed in the presence of any yeast, in particular not the yeast Hansenula polymorpha. It is therefore not a fermented biomass. The microalga Tetradesmus obliquus is also called Scenedesmus obliquus. For the purposes of the invention, the expression "extract of T. obliquus" is therefore understood to mean indifferently "extract of T. obliquus" or "extract of Scenedesmus obliquus".

[0018] Alternatively, within the meaning of the present invention, "extract of Tetradesmus sp." is understood to mean any extract obtained by any extraction method from any biomass of the microalga Tetradesmus dimorphus.

[0019] Each of the biomasses can be obtained from a culture of the corresponding microalgae in autotrophic mode, in heterotrophic mode, or in mixotrophic mode with respect to carbon. Advantageously, the autotrophic mode is implemented. The two species are not cultivated together. One and / or the other of the microalgae can be cultivated under controlled conditions within suitable systems such as open culture tanks of the “race-ways” or “open ponds” type or closed systems of the photobioreactor type. The photobioreactors used can be of any existing type such as horizontal tubular photobioreactors, vertical ones such as so-called “green wall panel” systems, flat or columnar photobioreactors. Preferably, the production of one or the other of the two biomasses is carried out within a closed culture system of the photobioreactor type. The culture of the microalgae is carried out according to the batch, fed-batch, continuous, semi-continuous, turbidostat or chemostat culture management modes.

[0020] The extraction can be carried out from a frozen or fresh biomass of T. obliquas or P. gyrans, preferably frozen. It can be dried or not dried before extraction. It is advantageously dried. Its quantity can range from 10 to 200g by weight, advantageously from 50 to 150g by weight and very advantageously from 100g by weight per 1L of extraction solvent. For the purposes of the invention, the term "dry biomass" means a dehydrated biomass comprising less than 15%, advantageously less than 10%, even advantageously less than 5% of water.

[0021] The biomass can be centrifuged and then filtered to remove the water before extraction. A solid-liquid extraction step can be carried out subsequently. Preferably, the Tetradesmus sp. extract or the Pavlova sp. extract is obtained by extraction in a solvent or solvent mixture chosen from water, acetone, hexane, ethyl acetate, methyltetrahydrofuran, 2-methyloxolane, heptane, an alcohol chosen from ethanol, methanol or isopropanol, a natural or branched oil, a glycol, a polyol and a water / alcohol or water / glycol mixture in a proportion of 99 / 1 to 1 / 99 (w / w) or any other solvent making it possible to extract all or part of the compounds of a hydrophobic and amphiphilic nature. Preferably, the Tetradesmus sp. extract or the Pavlova sp. extract. is obtained by extraction in a water / ethanol mixture in a proportion of 40 / 60 (w / w) to 1 / 99 (w / w), including 30 / 70 (w / w) and 20 / 80 (w / w), and very preferably in ethanol as the sole solvent.The solvent or solvent mixture is separated from the residual biomass after extraction by processes such as centrifugation, filtration and can subsequently be concentrated, or the solvent removed, by techniques such as vacuum evaporation or any other technique allowing the selective evaporation of the solvent in question. Alternatively, the Tetradesmus sp extract or the Pavlova sp extract is obtained by extraction under subcritical or supercritical conditions. Advantageously in this case, the extract is obtained by supercritical CO2 extraction. Advantageously, the extract is lipophilic, in particular oily.

[0022] The extraction can be carried out at a temperature ranging from 4°C to 300°C, and advantageously at a temperature ranging from 20°C to 40°C, including 35°C and room temperature, i.e. a temperature of 25°C. In a preferred embodiment of the invention and preferentially in the case of the extraction of the strain Tetradesmus sp., the extraction is carried out at a temperature of 40°C. Alternatively, in particular in the case of the extraction of Pavlova sp., the extraction temperature is 35°C.

[0023] In one embodiment of the invention, the extraction is carried out in water under subcritical conditions, at a temperature ranging from 100°C to 300°C, advantageously from 120°C to 250°C, still advantageously at 120°C. The extraction can be carried out at a given temperature or at successively increasing temperatures. In an advantageous embodiment of the invention, the extraction is carried out at a temperature of 120°C. In an alternative mode, it will be carried out according to a gradient of three increasing temperatures between 100°C and 200°C, such as 120°C, 140°C then 160°C or 110°C, 130°C then 150°C, or 120°C, 145°C then 170°C.

[0024] Extraction under "subcritical conditions" means extraction in the presence of water, under conditions of temperature above 100°C and pressure below 221 bars (22.1 MPa), the water remaining in the liquid state but having a viscosity and a surface tension lower than that of water at room temperature, increasing its dielectric constant. Thus, the extraction pressure is between 150 bars (15 MPa) and 250 bars (25 MPa), preferably between 200 (20 MPa) and 221 bars (22.1 MPa), advantageously in a pressurized extraction autoclave.

[0025] The extraction can be carried out by any method well known to those skilled in the art, advantageously by maceration in a solvent or mixture of solvents as described above.

[0026] The extraction time can be between a few minutes and several hours, in particular from 30 minutes to 4 hours, more advantageously from 1 hour to 3 hours, in particular it is 1 hour.

[0027] In all cases, the T. obliquas extract and / or the P. gyrans extract obtained is filtered. It is in oily form. It can be decolorized with activated carbon to remove the chlorophyll. In this case, it is filtered again. It can optionally be dried. Advantageously in this case, the drying step is carried out by lyophilization, vacuum drying, drum drying, or atomization, by fluidized bed coupling by any technique allowing encapsulation or microencapsulation via a support matrix and / or the formation of an emulsion. The dried extract according to the invention is then in powder form. It can be incorporated into a composition in powder form or in the oily form previously described.

[0028] Thus, in a first advantageous embodiment of the invention, the extract of T. obliquas is obtained as follows: a quantity of 100g of dried and filtered biomass of T. obliquas is extracted by maceration in 1L of ethanol as the sole solvent at a temperature of 40°C, for a period of 4 hours, according to example 1a).

[0029] In a second advantageous embodiment of the invention, a crude oily extract of T. obliquas or P. gyrans is obtained by supercritical CO2 extraction from a quantity of 100g / L of frozen biomass then centrifuged and filtered, in the presence of ethanol as co-solvent (10%), at a temperature of 50°C and a pressure of 150 bars (15 MPa) (Example 1b).

[0030] In a 3rd embodiment, the P. gyrans extract is obtained as follows: a quantity of 100g of dried and filtered biomass of P. gyrans is extracted by maceration in 1L of ethanol as the sole solvent at a temperature of 35°C, for a period of 1 hour, according to example 1c).

[0031] The liquid extract of T. obliquas or P. gyrans obtained, also referred to as an oily extract, can be incorporated into the composition according to the invention in a content ranging from 8% to 80%, advantageously ranging from 20% to 50%, still advantageously from 20% to 30% and very advantageously from 29% (Examples 1a to 1c).

[0032] In another embodiment, the two liquid extracts of T. obliquas and P. gyrans obtained above are incorporated into the same composition according to the invention in a content by weight relative to the final weight of the composition ranging from 4% to 40% each, advantageously ranging from 10% to 25%, still advantageously from 10% to 15%. In a particularly advantageous embodiment, the 2 liquid extracts of T. obliquas and P. gyrans obtained are incorporated into the same composition in a content by weight relative to the final weight of the composition of 14.5% for each extract, as detailed in example Id).

[0033] Alternatively, the liquid (oily) extract of T. obliquas is incorporated into the composition according to the invention in a content by weight relative to the final weight of the composition of 21.75% and the liquid extract of P. gyrans is incorporated in a content by weight relative to the final weight of the composition of 7.25%, as detailed in example 1c).

[0034] In a particularly advantageous embodiment of the invention, the extract of Tetradesmus sp., advantageously of T. obliquas, comprises a so-called non-significant quantity of lutein, it being understood within the meaning of the present invention by "non-significant quantity" a final quantity less than or equal by weight relative to the total weight of the extract of 3.45%, advantageously less than or equal to 1.72%, so that lutein is not the active molecule responsible for the alleged effects of the composition, still advantageously responsible for the effect of increasing immune defenses.

[0035] COMPOSITION

[0036] The composition according to the invention therefore comprises an extract of Tetradesmus sp., advantageously of T. obliquus, and / or an extract of Pavlova sp., advantageously an extract of P. gyrans, and at least one nutraceutically acceptable excipient.

[0037] The composition according to the invention comprises a weight ratio of the extract of Tetradesmus sp., advantageously of T. obliquus, and of the extract of Pavlova sp., advantageously P. gyrans, ranging from 100 / 0 to 0 / 100, advantageously from 75 / 25 to 25 / 75, inclusive 50 / 50, and advantageously it is 75 / 25.

[0038] For the purposes of the present invention, the term "nutraceutically acceptable excipient" means a non-toxic and inert excipient. At least one nutraceutically acceptable excipient is chosen from carrier agents, bulking agents, preservatives, acidifying agents, emulsifying agents, humectants, etc. metants, gelling agents, lubricating agents, coating or encapsulating agents, stabilizing or dispersing agents, sweetening agents and mixtures thereof. It can be ingested orally safely and without side effects. Carrier agents include maltodextrin, acacia gum, cellulose and its derivatives (methylcellulose, ethylcellulose and microcrystalline cellulose), calcium phosphate, inulins, flours (rice flour, coconut flour or other), starches and their derivatives, talc, or carob gum. Preservatives are chosen from sodium sorbate or sodium benzoate; acidifying agents are chosen in particular from citric acid or sodium citrate; emulsifying agents are chosen from lecithin, phospholipids, polyethylene glycols; humectants are chosen from glycerin, sorbitol, dextrose.Examples of bulking agents include mannitol, lactose, sorbitol, starch, microcellulose, hydroxypropylmethylcellulose, crosscarmelose, polyvinylpyrrolidone, calcium phosphate (anhydrous or hydrated di and tribasic), citric acid or tartaric acid, sodium, potassium or calcium carbonates, silicified cellulose, or acacia gum. Lubricating agents (anticaking agents) include magnesium stearate, stearic acid, lecithins, colloidal silica, rice extract, talc, glycerol dibehenate, or a bamboo extract titrated in silica. Coating or encapsulating agents may be chosen from gelatin, hydroxypropylmethylcellulose, pululan, beeswax or carnauba wax. Gelling agents can be chosen from starches, native or pregelatinized, carrageenans, pectin, alginates, agar-agar, xanthan gum or even gelatin.Examples of stabilizing or dispersing agents include alginates, acacia gum, and phospholipids. Sweetening agents include maltitol, xylitol, sucralose, sorbitol, agave syrup, glucose syrup, sucrose, fructose, stevia extract, honey, isomalt, and maltitol.

[0039] The excipient is advantageously present in the composition according to the invention in an amount, by weight relative to the total weight of the composition, of 1% to 90%, advantageously between 1% and 50%, still advantageously between 1.5% and 10%.

[0040] The composition according to the invention may further comprise at least one vegetable oil. For the purposes of the present invention, the term "vegetable oil" means any oil extracted from a plant or an algae, including a microalgae, in particular chosen from olive oil, rapeseed oil, linseed oil, sunflower oil, a medium chain triglyceride (MCT) oil. The term "medium chain triglycerides (MCT)" means esters of glycerol and saturated fatty acids, the hydrocarbon chain of which has from 6 to 12 carbon atoms. An MCT oil may thus be chosen from coconut oil, advantageously coconut oil, palm kernel and palm oil, but can be obtained from other fats or oils. Advantageously for the purposes of the invention, the vegetable oil is an MCT oil, more advantageously coconut oil, very advantageously coconut oil. In a particularly advantageous embodiment of the invention, the vegetable oil is present in the composition according to the invention in an amount, by weight relative to the total weight of the composition, of 20% to 90%, more advantageously of 60% to 90%, including between 70% and 80% and more advantageously of 70.5%.

[0041] The composition according to the invention may also comprise vitamin E. For the purposes of the present invention, the term "vitamin E" means a tocopherol chosen from α-tocopherol, γ-tocopherol, β-tocopherol or δ-tocopherol, or a tocotrienol chosen from α-tocotrienol, β-tocotrienol, γ-tocotrienol or δ-tocotrienol. Advantageously, it is α-tocopherol. In an advantageous embodiment, the vitamin E is present in the composition according to the invention in an amount, by weight relative to the total weight of the composition, of 0.15% to 1.25%, advantageously of 0.25% to 1%, very advantageously of 0.5%.

[0042] In one embodiment of the invention, the composition according to the invention thus comprises by final weight relative to the total weight of the composition at least: - A content of Tetradesmus sp. extract, advantageously T. obliquas, still advantageously of T. obliquas extract obtained in ethanol as the sole solvent, ranging from 8% to 79.85%, advantageously ranging from 20% to 50%, still advantageously from 20% to 30% and very advantageously 29%; -A coconut oil content ranging from 20% to 90%, advantageously ranging from 60% to 90%; - An α-tocopherol content ranging from 0.15% to 1.25%, advantageously from 0.25% to 1%, very advantageously from 0.5%.

[0043] This composition is very advantageously intended for use in reducing intestinal hyperpermeability and / or strengthening the intestinal barrier and / or preventing and / or improving intestinal transit and / or gastrointestinal disorders, and / or reducing stress, advantageously stress induced by intestinal discomfort and / or chronic stress generating intestinal discomfort, in particular making it possible to improve intestinal well-being, sleep and / or cognitive abilities.

[0044] Alternatively and advantageously for the above uses, the composition according to the invention comprises in final weight relative to the total weight of the composition: - A content of Tetradesmus sp. extract, advantageously T. obliquus, still advantageously of T. obliquus extract obtained in ethanol as the sole solvent, ranging from 4% to 40%, advantageously ranging from 10% to 25%, and very advantageously 19.33%; - A content of Pavlova sp. extract, advantageously P. gyrans, ranging from 4 to 40%, advantageously ranging from 10% to 25%, still advantageously from 10% to 15% and very advantageously from 9.33%; - A coconut oil content ranging from 20% to 90%, advantageously ranging from 60% to 90%; - An α-tocopherol content ranging from 0.15% to 1.25%, advantageously from 0.25% to 1%, very advantageously from 0.5%.

[0045] Alternatively, the composition according to the invention comprises a weight ratio of Tetradesmus sp. extract, advantageously T. obliquas, and Pavlova sp. extract, advantageously P. gyrans, of 75 / 25. The composition according to the invention may thus comprise by final weight relative to the total weight of the composition: - A content of Tetradesmus sp. extract, advantageously T. obliquus, still advantageously of T. obliquus extract obtained in ethanol as the sole solvent, ranging from 4% to 40%, advantageously ranging from 10% to 25%, and very advantageously 21.75%; - A content of Pavlova sp. extract, advantageously P. gyrans, ranging from 4 to 40%, advantageously ranging from 10% to 25%, advantageously 7.25%; - A coconut oil content ranging from 20% to 90%, advantageously ranging from 60% to 90%; - An α-tocopherol content ranging from 0.15% to 1.25%, advantageously from 0.25% to 1%, very advantageously from 0.5%.

[0046] This composition is advantageously intended for use in maintaining and / or increasing immune defenses, advantageously in humans.

[0047] Alternatively, a composition advantageously intended for its use to maintain and / or increase the immune defenses, advantageously of humans, comprises in final weight relative to the total weight of the composition, the weight ratio of Tetradesmus sp. extract and Pavlova sp. extract being advantageously 50 / 50,: - A content of Tetradesmus sp. extract, advantageously T. obliquus, still advantageously of T. obliquus extract obtained in ethanol as the sole solvent, ranging from 4% to 40%, advantageously ranging from 10% to 25%, still advantageously from 10% to 15% and very advantageously 14.5%; - A content of Pavlova sp. extract, advantageously P. gyrans, ranging from 4 to 40%, advantageously ranging from 10% to 25%, advantageously 14.5%; - A coconut oil content ranging from 20% to 90%, advantageously ranging from 60% to 90%; - An α-tocopherol content ranging from 0.15% to 1.25%, advantageously from 0.25% to 1%, very advantageously from 0.5%.

[0048] Still alternatively and advantageously for its use to maintain and / or increase the immune defenses, advantageously of humans, very advantageously by accelerating the return to tissue homeostasis during the immune response, the composition according to the invention comprises in final weight relative to the total weight of the composition: - A content of Pavlova sp. extract, advantageously P. gyrans, ranging from 8% to 79.85%, advantageously ranging from 20% to 50%, still advantageously from 20% to 30% and very advantageously 27%; -A coconut oil content ranging from 20% to 90%, advantageously ranging from 60% to 90%; - An α-tocopherol content ranging from 0.15% to 1.25%, advantageously from 0.25% to 1%, very advantageously from 0.5%.

[0049] In a particularly advantageous embodiment of the invention, the composition comprises a non-significant amount of lutein, it being understood here within the meaning of the present invention by "non-significant amount" a final amount by weight relative to the total weight of the composition less than or equal to 1% of lutein, preferably still less than or equal to 0.5%. Thus, lutein is not the active molecule responsible for the effects claimed for the composition, still advantageously responsible for the effect of increasing immune defenses.

[0050] The composition according to the invention may also comprise any compound active on the intestinal microbiota. In this respect, mention will be made of carotenoids, in particular lycopene, zeaxanthin, meso-zeaxanthin, astaxanthin, cryptoxanthin, flavoxanthin, neoxanthin, other α or β-carotenes, or fucoxanthin. Similarly, mention will be made of vitamin D, in particular vitamin D3, vitamin B, in particular B2 and / or B5, vitamin K, vitamin C, or branched-chain fatty acids, in particular Cn-C26.

[0051] The composition may also comprise omega-3 polyunsaturated fatty acids such as docosahexaenoic acid, docosapentaenoic acid, eicosate-traenoic acid, hexadecatrienoic acid, eicosapentaenoic acid, α-linolenic acid, stearidonic acid, eicosatrienoic acid, heneicosapen-taenoic acid, tetracosapentaenoic acid, tetracosahexaenoic acid or any mixture thereof, and in particular eicosapentaenoic acid ((5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentenoic acid or EPA; CAS number 10417-94-4; molar mass 302.451 g / mol; empirical formula C2oH3o02), docosahexaenoic acid (DHA; cas number 6217-54-5; molar mass 328.48g / mol; empirical formula C22H32O2) or their mixture.

[0052] Thus, any microalgae extract containing this type of polyunsaturated fatty acids can be included in the composition according to the invention in addition to the T. obliquas extract. The composition will advantageously comprise in this case a lipid extract chosen from a lipid extract of Phaeodactylum tricomutum known for its significant amount of EPA and / or a lipid extract of Haematococcus pluvialis, which also includes astaxanthin, and / or a lipid extract of Pavlova gyrans or Pavlova lutheri.

[0053] In the context of a complementary effect of prevention or treatment of intestinal dysbiosis, the composition according to the invention can be associated with dietary fibers such as cellulose, hemicellulose, starch, pectins, [3-glucans.

[0054] The composition according to the invention may be in liquid form (also referred to as oily form) or in powder form (solid form). Advantageously, the composition is in the form of a capsule, gel cap, tablet, tablet, candy, chewing gum, orodispersible tablet or sublingual tablet, granule, orodis-persible granule or sublingual granule, pill, lozenge, orodispersible lozenge or sublingual lozenge, energy bar, kibble, pâté, treat, granules, soft capsule, syrup, spray, ampoule, suspension, emulsion, hot or cold drink.

[0055] The composition according to the invention may be in powder form, the powder being obtained in this case from the oil form with a charge rate of between 15% and 40%, advantageously between 15% and 30%, by any technique known to those skilled in the art such as atomization, or by fluidized bed coupled with microencapsulation via a support matrix.

[0056] In the form of a powder, the composition according to the invention is then advantageously in the form of a cold-dispersible powder. It is advantageously in the form of a gel cap, a capsule, a tablet, a tablet, a candy, a chewing gum, an orodispersible tablet or a sublingual tablet, a granule, an orodispersible granule or a sublingual granule, a pill, a lozenge, an orodispersible lozenge or a sublingual lozenge, an energy bar, a kibble, a pâté, an animal food supplement, a treat or granules.

[0057] It is advantageously packaged in doses having a unit weight of between 50 mg and 2 g, advantageously between 100 mg and 500 mg, very advantageously between 100 mg and 250 mg.

[0058] When the composition according to the invention is in liquid (oily) form, it is advantageously packaged in the form of a soft capsule, a syrup, a spray, an ampoule, a suspension, an emulsion, a hot or cold drink.

[0059] The composition according to the invention is intended for animals, it being understood according to the invention by "animals" humans, domestic animals chosen from dogs and cats, and horses, cows, pigs, pigs. In an advantageous embodiment, the composition according to the invention is intended for humans.

[0060] In particular, the composition according to the invention is intended for humans. suffering from intestinal discomfort. Alternatively, the composition according to the invention is intended for humans with weakened immune defenses, advantageously due to external and / or internal stress.

[0061] In another particular embodiment, the composition according to the invention is intended for humans practicing a high-intensity sporting activity.

[0062] Thus, advantageously, it is administered at a daily dose in human equivalent of 20 to 1000mg, advantageously from 50 to 750mg / day, advantageously again from 50 to 500mg, and very advantageously from 50 to 250mg, inclusive 100mg / day and 150mg / day, the dose being in equivalent of the dose in oily (liquid) form. Thus, the daily quantity of lutein administered in human equivalent ranges from 0.06mg to 2.4mg, advantageously from 0.15mg to 1.5mg, advantageously again it ranges from 0.15mg to 0.75mg, inclusive 0.3mg.

[0063] In a particular embodiment of the invention, when the composition according to the invention comprises both an extract of Tetradesmus sp., advantageously of T. obliquas, still advantageously of an extract of T. obliquas obtained in ethanol as the sole solvent, and an extract of Pavlova sp., advantageously of P. gyrans, in a weight ratio of 50 / 50, the daily dose administered in human equivalent ranges from 20 to 1000 mg, advantageously from 50 to 750 mg, very advantageously from 100 mg to 500 mg, inclusive 200 mg.

[0064] When the composition is intended for animals other than humans, particularly when it is intended for domestic animals, it is advantageously packaged in the form of granules, pâté, treats, kibble. In this case, the daily dose ranges from 1 to 460 mg, advantageously from 3.5 to 300 mg / day, advantageously from 3.5 to 150 mg, including 25, 50 and 100 mg / day. The daily dose of lutein administered therefore ranges in this case from 0.0003 mg to 1.38 mg, advantageously from 0.0105 mg to 0.9 mg, again advantageously from 0.0105 mg to 0.45 mg, including 0.075, 0.15 and 0.3 mg.

[0065] The composition according to the invention is advantageously administered over a period ranging from 1 week to 6 weeks, advantageously from 1 week to 4 weeks.

[0066] USES

[0067] Another object of the invention therefore relates to the composition according to the invention for its use as a medicament.

[0068] In particular, another subject of the invention relates to the composition according to the invention or to an extract of Tetradesmus sp. as defined above for its use in reducing intestinal hyperpermeability and / or strengthening the intestinal barrier and / or preventing and / or improving intestinal transit and / or gastrointestinal disorders, advantageously those generated by intestinal hyperpermeability, and / or maintaining and / or increasing immune defenses and / or accelerating the return to tissue homeostasis during the immune response, and / or reduce stress, advantageously stress induced by intestinal discomfort and / or chronic stress generating intestinal discomfort.

[0069] The composition according to the invention or the extract of Tetradesmus sp. according to the invention is therefore useful for improving intestinal comfort, well-being, sleep and / or cognitive capacities, advantageously in animals, and even more advantageously in humans.

[0070] More particularly, another subject of the invention relates to the composition according to the invention or to an extract of Pavlova sp. as defined above for its use in maintaining and / or increasing immune defenses, advantageously by accelerating the return to tissue homeostasis during the immune response, and advantageously providing a complete immune response.

[0071] For the purposes of the invention, the term "reducing intestinal hyperpermeability" means reducing, in the presence of the composition according to the invention, damage to the colon and / or reducing tissue adhesions and / or reducing the severity of diarrhea induced by inflammation of the intestine. Advantageously, these reductions are evaluated via an index (Daily disease activity index), for example in the context of the preclinical test carried out on rats as detailed in example 2a), in response to treatment with sodium sulfate dextran (SSD) (Table 4) and in the presence of the composition according to the invention.

[0072] Alternatively, within the meaning of the invention, "reduce intestinal hyperpermeability" is understood to mean attenuating, in the presence of the composition according to the invention, the reduction in the average length of the colon fragments observed, for example, in the rats of the pre-clinical trial of example 2a) in response to the inflammation generated by the SSD and. Advantageously in this case, the SSD reducing the average length of the colon fragments by more than 40% in the absence of the composition according to the invention, the daily intake of said composition has the capacity to attenuate this percentage to at least 34% and up to 28.5% (Table 5).

[0073] In another embodiment, "reducing intestinal hyperpermeability" means, within the meaning of the present invention, reducing the quantity of specific fecal markers, for example measured in the context of the double-blind clinical trial consisting of administering daily for a period of 4 weeks a dose in capsule form comprising an equivalent of 100 mg of the composition according to the invention in liquid form (oil) or a placebo, as detailed in example 2c). Intestinal hyperpermeability is in particular evaluated via the measurement of the quantity of zonulin measured in the stools. Zonulin is a molecule produced by intestinal cells (enterocytes) whose role is to regulate intestinal tight junctions, structures located between enterocytes and which regulate the passage of substances from the intestine into the bloodstream: excess zonulin production leads to increased intestinal permeability.

[0074] For the purposes of the present invention, the term "strengthening the intestinal barrier" also means improving the intestinal microbiota and / or increasing the amount of immunoglobulin A (slgA) in the blood. In one embodiment of the invention, this involves an improvement of the intestinal microbiota. Advantageously, in this case, the intestinal microbiota is evaluated by genomics following daily oral administration of the composition according to the invention, for example in the context of the clinical trial in humans described in example 2c). Advantageously again, this is the composition comprising an extract of T. obliquas, advantageously that described in example 1a).

[0075] In another embodiment, an increase in the amount of immunoglobulin A is measured in the blood, for example of participants in the clinical trial of example 2c) having received daily the composition according to the invention in comparison with the administration of the placebo.

[0076] Furthermore, within the meaning of the present invention, the term "improving intestinal transit" means increasing colon motility. In an advantageous embodiment of the invention, the increase in colon motility is measured in the context of the pre-clinical trial in rats (Example 2a)), via the measurement of the isotonic contractions of the colon fragments analyzed (Example 2b)). Thus, the composition according to the invention has the capacity to maintain the average amplitude of the isotonic contractions up to 81.4% compared to the control not treated with SSD, while maintaining an average frequency of contractions equivalent to the control not treated with SSD (Table 6, example 2b)). The composition according to the invention is therefore effective in improving intestinal transit.

[0077] In an alternative embodiment of the invention, the term "strengthening the intestinal barrier" and / or "improving intestinal transit" is understood to mean increasing the amount of short-chain fatty acids (SCFAs). Advantageously, in this case, the increase in the amount of SCFAs is detected in the stools, for example in the context of the clinical trial described in example 2c).

[0078] For the purposes of the present invention, the expression "preventing and / or improving gastrointestinal disorders" also means improving at least one of the disorders chosen from diarrhea and / or constipation and / or colitis and / or bloating and / or gas and / or inflammation of the colon and / or intestinal dysbiosis and / or intestinal pain and / or fatigue and / or weight loss.

[0079] By strengthening the intestinal barrier, reducing intestinal hyperpermeability and preventing or improving gastrointestinal disorders, the composition according to the invention improves intestinal comfort, advantageously of animals, even more so dramatically humans.

[0080] In addition, within the meaning of the invention, the expression "maintaining the immune defenses" means limiting, in the presence of the composition according to the invention, a reduction in the immune response induced by internal and / or external stress, advantageously by strengthening both the innate and adaptive immune response. Here, the term "external stress" is understood to mean, in particular but not exclusively, stress such as intense physical activity, taking medication or a benign pathology other than cancer or an autoimmune disease. The term "internal stress" is understood to mean, in particular but not exclusively, a dietary imbalance, a hormonal change, stress or anxiety.

[0081] In a first embodiment, this involves maintaining the detected quantity of cells chosen from leukocytes and / or lymphocytes and / or monocytes and / or neutrophil granulocytes of at least 30%, advantageously at least 40% and very advantageously at least 50% in the presence of the composition according to the invention in comparison with the detected quantity of the same cells without the composition according to the invention, also subjected to immunodepression. Still advantageously, this involves maintaining the quantity of said cells measured in the plasma of a population of rats subjected to immunodepression by treatment with cyclophosphamide, under the conditions as detailed in example 3a). The composition according to the invention comprising the extract of T. obliquas, advantageously the composition according to example 1a), and the composition according to the invention comprising an extract of P.gyrans, advantageously the composition according to example 1c), are effective in maintaining immune defenses by limiting the immunosuppression induced by the treatment (Table 8). Each of these two compositions is therefore effective on both the adaptive and innate immune response.

[0082] Furthermore, within the meaning of the present invention, the expression "increasing the immune defenses" means reducing inflammation by reducing the quantity in the blood of at least one pro-inflammatory marker chosen from interleukins IL1 [3, IL6, TNFa (Tumor Necrosing Factor), and / or by increasing the quantity in the blood of at least one marker qualified within the meaning of the invention as an anti-inflammatory marker chosen from interleukins 2, 4, 5, 7, 8, 10, 12, 13, in the presence of the composition according to the invention.

[0083] In one embodiment of the invention, the reduction in the quantity of at least one pro-inflammatory blood marker is measured in the context of the preclinical test in rats as detailed in example 3a) in the presence of the composition according to the invention comprising an extract of T. obliquas. Advantageously in this case, it is the reduction in the quantity of blood interleukin IL1[3 measured two days after pulmonary infection by the bacterium Pseadomonas aeruginosa in the presence of the composition according to example 1a) (Table 9).

[0084] In another embodiment of the invention, the reduction in the quantity of at least one pro-inflammatory blood marker and / or the increase in the quantity of at least one anti-inflammatory marker chosen from interleukins 2, 4, 5, 7, 8, 10, 12, 13 is measured in the context of the clinical trial as described in example 3b) consisting of the daily intake of the composition according to the invention comprising an extract of T. obliquas, advantageously the composition according to example 1a).

[0085] In another embodiment of the invention, "increasing the immune defenses" means increasing the quantity of NKT and / or CD4 and / or CD8 lymphocytes. NKT (Natural Killer T) lymphocytes are a heterogeneous group of T lymphocytes capable of producing large quantities of cytokines and are endowed with cytotoxic activity. CD4 and CD8 lymphocytes are cytotoxic lymphocytes essential for the adaptive response, which possess the CD4+ and CD8+ markers allowing the recognition of abnormal or foreign (pathogenic) cells. In a particularly advantageous embodiment, this is an increase in the quantity of NKT and / or CD4 and / or CD8 lymphocytes in the lungs following bacterial infection by Pseudomonas aeruginosa of the rat population of the preclinical trial detailed in Example 3a), in the presence of the composition according to the invention comprising an extract of T.obliques, advantageously still the composition of example 1a) (Table 10), in comparison with the measured quantities of the same cells in the lungs of the groups of rats having received the placebo composition (Group 1) (i.e. without composition according to the invention).

[0086] In yet another embodiment of the invention, "increasing immune defenses" is understood to mean accelerating the return to tissue homeostasis during the immune response.

[0087] “Accelerate the return to tissue homeostasis during the immune response” means in the context of the present invention preventing tissue necrosis induced by dying neutrophils during the immune response. In a particularly advantageous embodiment of the invention, the term "accelerating the return to tissue homeostasis during the immune response" means increasing the quantity of efferocytic macrophages in the lungs, for example of the population of rats infected with the bacterium Pseudomonas syringae, as detailed in Example 3a) (Table 10) in the presence of the composition according to the invention and in comparison with the quantity of efferocytic macrophages measured in the lungs of the group of rats having received the placebo composition (Group 1). Very advantageously, the increase in the quantity of efferocytic macrophages is measured 2 days after pulmonary infection with P. aeruginosa in the presence of the composition comprising an extract of P. gyrans, advantageously the composition according to Example 1c).

[0088] In another particularly advantageous embodiment of the invention, "accelerating the return to tissue homeostasis during the immune response" means reducing the bacterial load measured in the lungs of the population of mice infected with P. aeruginosa in the presence of the composition according to the invention, 2 days after infection, in particular under the conditions detailed in Example 3a). Advantageously, the measured bacterial load is reduced within the groups of mice having received the daily intake of the composition comprising an extract of P. gyrans, advantageously the composition according to Example 1c), in comparison with the bacterial load measured within the group of mice having received a daily intake of the placebo composition (Group 1) (Example 3a), Table 11).

[0089] The composition according to the invention comprising both an extract of Tetradesmus sp., advantageously T. obliquas, and an extract of Pavlova sp., advantageously P. gyrans, being effective both in maintaining and increasing adaptive and innate immune responses, and overall in maintaining and increasing immune defenses, on the one hand, and in accelerating the return to tissue homeostasis on the other hand, is therefore useful for providing a complete immune response.

[0090] In a particular embodiment, the composition therefore comprises both an extract of Tetradesmus sp. and an extract of Pavlova sp. This composition makes it possible to provide a complete immune response with sequential response kinetics of the extract of Pavlova sp., advantageously P. gyrans then of the extract of Tetradesmus sp., advantageously T. obliquus.

[0091] Furthermore, for the purposes of the present invention, the term “reduce stress” means a reduction in at least one stress biomarker chosen from α-amylase (sAA), chromogranin A (CgA), lysozyme, blood-derived neurotrophic factor (BDNF), adrenocorticotropic hormone (ACTH) or cortisol in the presence of the composition according to the invention. In one embodiment, this is a reduction in the amount of at least one of the above biomarkers measured within a population of individuals in the context of the clinical trial described in example 2c) in response to the daily oral administration of the composition according to the invention comprising the extract of T. obliquus, advantageously the composition according to example 1a). Advantageously, this is a decrease in at least one of the above biomarkers (Example 4).

[0092] By reducing stress, the composition according to the invention and the extract of T. obliquus, is also useful for improving well-being and sleep, advantageously in humans.

[0093] Finally, for the purposes of the present invention, the expression “improve cognitive abilities” means increasing at least one of the cognitive functions chosen from spatial working memory, attention and vigilance, executive function, or episodic memory and / or decreasing at least one quantity chosen from the quantity of interleukin 6 and / or the amount of C-reactive protein (hs-CRP) and / or the amount of tumor necrosis factor alpha (TNFα) in the blood and / or cerebral cortex. C-reactive protein is a predictive marker of cognitive function and an elevated level of this protein is a sign of dementia in healthy human populations of middle to old adulthood. Interleukin 6 is a mediator of C-reactive protein synthesis. TNFα is a proinflammatory cytokine with a role in cerebral cortex inflammation.

[0094] Thus, in a first embodiment of the invention, the effect of the composition according to the invention on cognitive abilities is demonstrated in vivo in the context of a pre-clinical trial in rats in a D-Galactose model and consisting of the oral administration of the composition according to the invention. Galactose induces, via chronic intoxication of the cerebral cortex (lipid peroxidation), learning deficits and / or passive avoidance in rats as well as inflammation resulting in an increase in TNFa and IL-6 in the cerebral cortex and plasma. Advantageously, the pre-clinical trial is conducted in the presence of the composition comprising an extract of Tetradesmus sp., advantageously T. obliquas, still advantageously the composition according to example 1a). Very advantageously, the quantity of TNFa and IL-6 are evaluated by ELIS A immunoassay.

[0095] In another embodiment of the invention, the effect of the composition according to the invention on cognitive abilities is demonstrated in vivo in the context of a clinical trial in humans consisting of the oral administration of the composition comprising an extract of Tetradesmus sp., advantageously T. obliquus, and advantageously the composition according to example 1a). The cognitive functions chosen from spatial working memory, attention and vigilance, executive function, and episodic memory are evaluated by means of dedicated tests using different COMPASS (Computerized Pilot Aptitude Screening System) modules as detailed below: - Corsi block of the COMPASS module to assess spatial working memory; - (Kessels, RPC; van Zandvoort, MJE; Postma, A.; Rappelle, LJ; de Haan, EH F (2000). “The Corsi Block-Tapping Task: Standardization and Normative Data”. Applied Neuropsychology. 5 7 (4): 252-258); - Attention and vigilance are assessed via reaction time by the Digit Vigilance Task module of the COMPASS test; - Change in executive function, assessed via the Stroop module of the COMPASS test (Stoop, John Ridley (1935) "Studies of interference in serial verbal reactions", Journal of Experimental Psychology, 18 (6): 643-662, doi:10.1037 / h0054651); - Change in episodic memory assessed by the Stroop module of the test COMPASS (Stoop, John Ridley (1935) "Studies of interference in serial verbal reactions", Journal of Experimental Psychology, 18 (6): 643-662, doi:10.1037 / h0054651); - Change in cognitive and perceptual abilities assessed by the Neurotracker light reaction test.

[0096] Associated with the effects of strengthening the intestinal barrier and reducing intestinal hyperpermeability in particular, the composition according to the invention, through its effect on strengthening immune defenses, constitutes a complete food supplement making it possible to facilitate intestinal transit and improve intestinal comfort, fight against infections, but also improve the well-being, sleep and cognitive functions of humans and animals.

[0097] Another subject relates to a method for reducing intestinal hyperpermeability and / or strengthening the intestinal barrier and / or improving intestinal transit and / or preventing and / or improving gastrointestinal disorders, advantageously those generated by intestinal hyperpermeability, and / or maintaining and / or increasing immune defenses and / or reducing stress, advantageously stress induced by intestinal discomfort and / or chronic stress generating intestinal discomfort, comprising the oral or sublingual administration to a patient in need thereof of an effective amount of a composition according to the invention or of an extract of Tetradesmus sp. according to the invention. The patient may be an animal, including a human.

[0098] The method is thus effective in improving well-being, intestinal comfort, sleep and / or cognitive abilities, advantageously in animals, even more advantageously in humans, but also in providing a complete immune response.

[0099] In an advantageous embodiment of the invention, the method of the invention comprises the steps of: - Selection of an animal, advantageously a human, advantageously again who needs it and / or who wants it, particularly suffering from or reporting one or more gastrointestinal disorders chosen from diarrhea and / or constipation and / or colitis and / or bloating and / or gas and / or inflammation of the colon and / or intestinal pain and / or dysbiosis of the intestinal microbiota and / or fatigue and / or weight loss, and / or suffering from a drop in immune defenses and / or wishing to strengthen their immune defenses, in particular humans practicing a high-intensity sporting activity. - oral or sublingual administration of an effective amount of a composition comprising an extract of Tetradesmus sp., advantageously of T. obliquas and / or an extract of Pavlova sp., advantageously P. gyrans, at least one nutraceutically acceptable excipient, at least one vegetable oil and at least vitamin E, advantageously to reduce intestinal hyperpermeability and / or strengthen the intestinal barrier and / or improve intestinal transit and / or prevent and / or improve gastrointestinal disorders, advantageously those generated by intestinal hyperpermeability and / or maintain and / or increase immune defenses and / or reduce stress, advantageously stress induced by intestinal discomfort and / or chronic stress generating intestinal discomfort.

[0100] Another subject relates to a method for maintaining and / or increasing immune defenses, advantageously by accelerating the return to tissue homeostasis during the immune response, more particularly to provide a complete immune response, comprising the oral or sublingual administration to a patient in need thereof of an effective amount of a composition according to the invention or of an extract of Pavlova sp. according to the invention, advantageously an extract of Pavlova gyrans. The patient may be an animal, including a human. List of cited documents

[0101] Lacy BE, Mearin F., Chang L., Chey WD, Lembo AJ, Simren M., Spiller R. 2016. Bowel Disorders. Gastroenterology, 150:1393-1407.

[0102] EXAMPLE

[0103] Example 1: Obtaining a composition according to the invention

[0104] Example la) Extract of Tetradesmus sp. and composition comprising it:

[0105] The strain of Tetradesmus sp used in the context of the invention was first isolated in Germany in 1976. Two distinct strains were used in the context of the invention and were obtained from the collections of the University of Austin, Texas, USA (Culture Collection of Algae, strain UTEX 393) and from the Culture Collection of Algae & Protozoa (CCAP 276 / 48).

[0106] The above strains were indifferently cultivated in autotrophic mode in a photobioreactor, under controlled conditions of pH, light and temperature. The T. obliquus biomass obtained was frozen and then dried. A solid-liquid extraction step was then implemented: a quantity of 100g / L of biomass was extracted by maceration in ethanol at a temperature of 40°C, for a period of 4 hours. The liquid extract thus obtained (also called oily extract) was incorporated into a composition as below:

[0107] The liquid extract was mixed with coconut oil in a final amount by weight of 29% relative to the total weight of the composition (70.5% coconut oil). A final amount by weight of 0.5% relative to the final weight of the composition of α-tocopherol was added to the mixture. At least one nutraceutically acceptable excipient was incorporated into the composition. The composition obtained is in oily (liquid) form.

[0108] This composition was then tested in the pre-clinical studies described in examples 2 and 3a).

[0109] Example 1b) Extract of Tetradesmus su. and composition comprising it:

[0110] A crude oily extract of Tetradesmus obliquus was obtained by supercritical CO2 extraction from a quantity of 100g / L of frozen then centrifuged and filtered biomass of one of the strains described in example 1a), in the presence of ethanol as cosolvent (10%), at a temperature of 50°C and a pressure of 150 bars (15MPa).

[0111] This extract was mixed with a final amount by weight of coconut oil of 70.5% relative to the total weight of the composition, and 0.5% by weight relative to the final weight of the composition of α-tocopherol was added to the mixture. At least one nutraceutically acceptable excipient was incorporated into the composition. The composition obtained is in oily (liquid) form.

[0112] Example 1c) Extract of Pavlova sp. and composition comprising it:

[0113] The Pavlova sp. strain used in the context of the invention was isolated for the first time in 1966 in the Atlantic Ocean and was obtained from the Culture Collection of Algae & Protozoa (CCAP 940 / 2). The strain was cultivated in autotrophic mode in a photobioreactor, under controlled conditions of pH, light and temperature. The Pavlova sp. biomass obtained was frozen and then dried. A solid-liquid extraction step was then implemented: a quantity of 100g / L of biomass was extracted by maceration in ethanol at a temperature of 35°C, for a period of 1 hour. The liquid extract thus obtained (also called oily extract) was incorporated into a composition as below:

[0114] The liquid extract obtained was mixed with coconut oil in a final amount by weight of 29% relative to the total weight of the composition (70.5% coconut oil). A final amount by weight relative to the final weight of the composition of 0.5% α-tocopherol was added to the mixture. At least one nutraceutically acceptable excipient was incorporated into the composition. The composition obtained is in oily (liquid) form and was used in the pre-clinical trial detailed in Example 3a).

[0115] Example Id) Composition comprising an extract of Tetradesmus sp. and Pavlova sp.: each of the 2 oily extracts obtained in examples la) and le) was mixed with coconut oil in a final quantity by weight for each extract of 14.5% relative to the final weight of the composition (70.5% coconut oil), i.e. a ratio by weight of extract of T. obliquus and P. gyrans respectively of 50 / 50. A final quantity by weight relative to the final weight of the composition of 0.5% of α-tocopherol was added to the mixture. At least one nutraceutically acceptable excipient was incorporated into the composition. The composition obtained is in oily (liquid) form.

[0116] Example 1a) Composition comprising an extract of Tetradesmus sp. and Pavlova sp.: the oily extracts of T. obliquus and P. gyrans obtained in examples 1a) and 1c) were respectively mixed with coconut oil in a final quantity by weight of 21.75% and 7.25% relative to the final weight of the composition (70.5% coconut oil), i.e. a weight ratio of T. obliquas and P. gyrans extract respectively of 75 / 25. A final quantity by weight relative to the final weight of the composition of 0.5% of α-tocopherol was added to the mixture. At least one nutraceutically acceptable excipient was incorporated into the composition. The composition obtained is in oily (liquid) form.

[0117] Example 2: Effect of the composition according to the invention comprising an extract of Tetradesmus sp. on intestinal hyperpermeability and colon motility.

[0118] Example 2a) Effect on weight / length ratio, weight, length and colon lesions: improvement of intestinal hyperpermeability in rats.

[0119] Protocol: A pre-clinical study in rats was conducted as follows: a population of 50 8-week-old male C57B1 / 6J mice (Charles River Labs, St Germain sur l'Arbresle, France) was acclimatized for a period of 5 days after arrival in the laboratory in ventilated cages, in groups of 5 mice per cage. The acclimation conditions consisted of normal lighting (12 hours of light per day), a temperature of 22°C (± 2°C) and a relative humidity of 50% (± 10%). Their bedding was changed once a week. During the acclimatization and experimental phases, the mice were fed a standard diet (SAFE) and plain water ad libitum.

[0120] The above 9-week-old male mice were randomly divided into 5 groups of 10 mice each. Four groups were treated with sodium sulfate dextran (SSD) by adding 3% SSD to the plain water provided for a period of 6 days. SSD is a molecule mimicking the immune and histopathological characteristics of Bowel's inflammatory syndrome. A 5th group did not receive SSD treatment. Three of the four SSD-treated groups received daily for 21 days a dose of the composition comprising the T. obliquas extract (Example 1a) of 308, 617 or 1542 mg / mouse / day (equivalent to 50, 100 or 250 mg / human / day). The 4th SSD-treated group received a daily dose of a placebo composition (no T. obliquas extract, but MCT oil + a-tocopherol). After 21 days, all groups of mice were euthanized and their colons were collected, cut longitudinally, and their contents collected.Colons were weighed and their length measured (Table 5). Colon lesions in the SSD-treated groups were assessed immediately after euthanasia. The following macroscopic parameters were analyzed and classified according to their severity (Table 1): . - Colon damage from 0 (normal) to 3 (severe); - Tissue adhesion from 0 (no adhesion) to 2 (severe adhesion); - Stool consistency from 0 (formed stools) to 2 (severe diarrhea).

[0121] The results of the macroscopic parameters are presented in Table 5.

[0122] A 0.5 cm fragment of colon was taken from the region showing inflammation, fixed in a formaldehyde solution (4%) for histological analysis. A portion of the residual tissues was frozen at -80°C until analysis. Weekly monitoring of the mice's weight (Table 2) and their water and food intake was carried out (Table 3). The presence of blood in the stools and the consistency of the stools were analyzed every day during the 21-day period, which combined with the weekly analysis of weight loss, made it possible to establish a daily disease index (Daily disease index) from 0 to 4 according to the following classification.

[0123] [Tables 1] Score Weight loss (%) Stool consistency Presence of blood 0 None Normal Normal 1 1-5 Loose stools Presence of blood 2 5-10 Diarrhea Presence of blood 3 10-20 Diarrhea Significant bleeding 4 >20 Diarrhea Significant bleeding and rectal prolapse

[0124] Result:

[0125] Table 2: Evaluation of average weight loss during treatment in percentage relative to untreated control at time 0 (AVG %)

[0126] [Tables2] AVG (%) / days 0 7 14 15 16 17 18 19 20 21 Group 1 100.0 103.3 108.3 109.2 108.3 108.7 110.4 110.0 109.6 109.6 Group 2 placebo 98.7 102.9 104.1 105.0 102.5 102.9 102.9 96.6 90.8 85.8 Group 3 dose 50 100.4 104.2 109.2 109.2 107.1 107.5 106.7 100.0 94.8 91.2 Group 4 dose 100 99.6 100.4 104.2 105.0 100.4 101.7 100.0 94.9 89.1 85.8 Group 5 dose 250 99.6 102.5 105.0 105.8 102.5 103.3 103.3 97.9 92.0 87.0

[0127] Group 1 of mice: untreated control (SSD);

[0128] Group 2 of mice: Control treated with SSD with placebo composition;

[0129] Group 3 of mice: Supplementation with composition at dose 50 (dose of 50mg / day / human);

[0130] Group 4 of mice: Supplementation with composition at dose 100 (dose of 100mg / day (human);

[0131] Group 5 of mice: Supplementation with composition at dose 250 (dose of 25 0mg / day / human).

[0132] Conclusion: SSD treatment only slightly modified the weight of the mice during the treatment, i.e. a weight loss of 15% was measured after 21 days in the mice treated with SSD (Group 2 placebo). On the other hand, supplementation with the composition according to the invention (Composition according to example 1a) in the mice treated with SSD did not induce any weight variation in comparison with the mice in group 2 (treated with SSD with placebo composition), even after 21 days of treatment (Groups 3, 4, 5). The daily intake of the composition according to the invention at the dose tested has no impact on weight.

[0133] Table 3: Dietary control during treatment

[0134] [Tables3] Quantity of food ingested (g / mouse / day) in % compared to the untreated control (group 1) Volume of water ingested (mL / mouse / day) in % compared to the untreated control (group 1) Group 1 100 100 Group 2 placebo 76.27 87.91 Group 3 dose 50 87.45 93.05 Group 4 dose 100 84.06 96.97 Group 5 dose 250 84.40 94.86

[0135] Conclusion: The SSD-treated mouse groups had almost no change in their water intake (Groups 2 to 5). The average food intake was reduced in the SSD-treated mice by less than 25% but was comparatively less reduced in the mice that received the supplementation with the composition according to the invention (Groups 3 to 5).

[0136] Table 4: DAI index (Daily disease activity index):

[0137] [Tables4] Day 0 1 2 3 4 5 6 7 Group 1 (untreated) 0 0 0.1 0 0 0.1 0.2 0 Group 2 (placebo) 0 0.7 1.3 1 1.7 4 6.3 7.2 Group 3 dose 50 0 0.4* 0.8* 0.8**** 1.4 4 2**** 4 5**** 4 D**** Group 4 dose 100 0 0.6 1.2 1.3* 2.3 3.3 5.3**** 5.6**** Group 5 dose 250 0 0.3 1.1 0.9 1.2 3.3*** 5.8**** g 1****

[0138] (*p<0.05; ***p<0.001; ****p<0.00001 p values ​​test 2-way Anova and Bonferroni's post-hoc test)

[0139] Conclusion: SSD treatment significantly increased the index in 7 days (Group 2) compared to the untreated control group (Group 1). On the other hand, supplementation with the composition according to the invention (Composition according to Example 1a)) limited this increase, the index representing 57% (Group 3) and 77.8% (Group 4) of the index calculated for the treated group 2, after 7 days. The composition according to the invention is therefore effective in mitigating colon damage, tissue adhesion and diarrhea induced by SSD treatment.

[0140] Table 5: Macroscopic evaluations of the analyzed colon fragments

[0141] [Tables5] Mean colon weight (W)(mg) Colon length (cm) as % of untreated control (Group 1) (L) (AVG) Group 1 (untreated) 225.3 100 Group 2 (placebo) 223.7 59.5 Group 3 (dose 50) 229.7 68.6 Group 4 (dose 100) 219.7 65.5

[0142] Conclusion: SSD treatment reduced the average length of the colon by more than 40% (Group 2). The daily intake of the composition according to the invention comprising an extract of T. obliquus (Ex. la)) in the diet, on the other hand, made it possible to reduce this percentage to 31.4% (Group 3).

[0143] Example 2b) Effect on colon motility (isotonic contractions)

[0144] Protocol: A portion of the colon fragments dissected according to the protocol of Example 2a) were washed and then incubated in a Krebs-Ringer solution for a period of 30 minutes at a temperature of 37°C, attached to an isotonic sensor (MLT7006 Isotonie Transducer, Hugo Basile, Comerio, Italy) and immersed in a bath maintained at 37°C and comprising the same Krebs-Ringer solution. A force of 10 mNewton (mN) was applied to the colon fragments. Isotonic contractions were recorded via software (Labchart, AD Instruments) for a period of 10 minutes.

[0145] Result: The results are expressed as the mean number of contractions compared to the untreated control with SSD (Group 1). A statistical test (Student, one pair or two-way Anova) was performed. The results are considered significant when p<0.05.

[0146] [Tableauxô] Amplitude (mN) in % compared to group 1 (AVG) Frequency of contractions (number of contractions / minute) in % compared to group 1 (AVG) Group 1 (untreated) 100 100 Group 2 (placebo) 17.3 120.2 Group 3 (dose 50) 81.4* 104.5 Group 5 (dose 250) 80.8* 102

[0147] (* p<0.05 post hoc ANOVA one-way statistical analysis (Bonferroni's post-hoc test))

[0148] Conclusion-. SSD treatment by altering the excitability of sensorimotor neurons disrupted enteric cholinergic neurotransmission and suppressed smooth muscle reactivity, inducing a decrease in contractions of the colon fragments tested. In SSD-treated mice having received daily supplementation with composition according to the invention (Example 1a)), colon motility was restored by increasing the amplitude of contractions of the colon fragments tested, without impacting the frequency of these contractions which remains similar to that measured in the control not treated with SSD.

[0149] The composition according to the invention comprising an extract of T. obliquas is thus effective in improving colon motility, and therefore in improving intestinal transit.

[0150] Example 2c) Clinical evaluation in humans of the effect of the composition according to the invention on gastrointestinal health (intestinal barrier, intestinal transit):

[0151] Protocol: A human clinical trial was conducted on a population of 50 healthy individuals aged 18 to 55 years, with a body weight index (BMI) between 18.0 and 29.9 and presenting mild to moderate gastrointestinal distress confirmed by a positive response to the Rome IV criteria (Lacy et al., 2016. Gastroenterology, 150:1393-1407). The clinical trial consisted of administering daily a dose equivalent to 100 mg of the composition comprising the T. obliquas extract according to example 1a) in capsule form.

[0152] The exclusion criteria were as follows: -BMI >30.0 or <18.0; - Smoking or using other tobacco products; - Diagnosed intestinal diseases; - Pregnant or breastfeeding people; - Regular use of statins, metformin, steroids, NSAIDs or monoamine oxidase (MAO) inhibitors; - Clinically diagnosed mental disorders (clinical depression, bipolar disorder, etc.)

[0153] Participants were excluded from the clinical trial if they no longer met the inclusion criteria (or entered the exclusion criteria during the trial). Measurements of weight, height, hips, as well as blood pressure, body temperature and heart rate were taken at time 0 (Initial recruitment visit), 2 weeks before the start of the trial, on the day of the start of the clinical trial and 2 weeks and 4 weeks after the start of the trial.

[0154] A measurement of the following fecal and blood biomarkers was carried out following a blood sample taken from each participant at the same times as above: - Analysis of the permeability and functionality of the intestinal barrier by stool sampling and dosages of short-chain fatty acids (SCFA), immunoglobulin A (slgA), alpha-1 antitrypsin and zonulin; - Analysis of the intestinal microbiota by genomics (in particular, analysis of the presence and levels of Bifidus and Lactobacillus, Escherichia coli, Staphylococcus aureus via 16S ANR sequencing).

[0155] Example 3: Effect of the composition according to the invention on the maintenance and increase of immune defenses in rats and in humans

[0156] Example 3a) Effect of maintaining immunity in immunocompromised rats and improvement of the immune response in response to pulmonary infection by P. ae-ruginosa:

[0157] Protocol: A pre-clinical trial in mice was conducted as follows: a population of 90 female mice (Janvier-Labs) aged 6 weeks at the start of the trial was randomly divided into 7 separate groups of 12 mice each. At the start of the trial (D-10), a blood sample was taken from 6 mice from each group to measure the quantity of leukocytes, lymphocytes, monocytes and neutrophil granulocytes in the blood (plasma). Three of the 7 groups then received a daily oral dose of the composition according to the invention comprising the Tetradesmus obliquas extract described in Example 1a) as part of their daily dietary intake (Group 2: dose of 50 mg / kg body weight in human equivalent; Group 3: dose of 100 mg / kg body weight in human equivalent and Group 4: dose of 250 mg / kg in human equivalent).Control group 1 received a daily dose of MCT oil instead of the composition according to the invention (placebo composition). Two other groups received a daily oral dose of the composition according to the invention comprising the Pavlova gyrans extract described in example 1c) as part of their daily dietary intake (Group 5: dose of 50mg / kg of human equivalent body weight; Group 6: dose of 250mg / kg in human equivalent).

[0158] Six days after the blood sample was taken at the start of the trial (D-4), immunosuppression treatment began for a period of 3 days, the treatment consisting of 2 intrapulmonary injections of cyclophosphamide, a 1st injection at a concentration of 150 mg / kg mouse weight at time D-4 then a 2nd injection (100 mg / kg mouse weight) at time D1 (9 days after the start of the trial).

[0159] At time DO (10 days after the start of the test), a blood sample was taken from 6 mice of the 6 groups to measure the amount of blood leukocytes, lymphocytes, monocytes and neutrophil granulocytes (plasma). The results are shown in Table 8 (n=6).

[0160] Immediately following the blood collection at DO, the groups of mice except for one control group (Group 7) were infected by intranasal inoculation of Pseudomonas aeruginosa (1 x 105 CFU / mouse) (dilution in Phosphate Buffer Saline buffer). Two days after inoculation (D+2), a blood sample was taken from groups 1 to 6 of mice (Table 8). At the same time (D+2), lung fragments from 6 mice from groups 1 to 6 were taken for measurement of the bacterial load (CFU) analysis by flow cytometry.

[0161] The measurement of the bacterial load in the lungs was carried out after grinding the lung fragments in PBS buffer and diluting the homogenates obtained in the PBS buffer. The samples obtained were deposited on an Agar plate comprising the tryptone soy agar culture medium and the plates placed for a period of 24 hours at a temperature of 37°C. The results of the measurement of the bacterial load are presented in Table 11.

[0162] For the analysis of lung fragments by flow cytometry, the lung fragments were dilacerated, the pulmonary blood cells were lysed by a lysis buffer, stained by Live Dead Blue-UV and then fixed by paraformaldehyde (3.6%) in the presence of a mixture of specific antibodies comprising all the cell markers below (and their commercial references: Table 7). The cells were counted by flow cytometry. The results are presented in Table 10.

[0163] [Tables?] CD45-Viogreen (130-110-665) SiglecF-PE (130-112-332) CD 11b-APC (130-113-802) CD64-PeVio (770 130-119-659) CDllc-Vioblue (130-110-843) I-Ab-PerCP Cy5.5 (116416) LY6G-BV711 (127643) LY6C-AF700 (128024) CD3-FITC (130-119-798) CD4-BV605 (100451) CD8-APCVio770 (130-120-806)

[0164] A measurement of inflammatory interleukins II[3 in the blood was also carried out (Table 9). The weight of the mice (12 mice from each group) was monitored daily throughout the duration of the trial (Table 12).

[0165] Results:

[0166] Table 8: Mean number of immune cells (xl06 cells / mL) measured in the blood (mean % relative to the quantity of the cell type at time D-10 of group 1 (placebo control (MCT Oil)).

[0167] [Tables8] Leukocyte Lymphocyte Monocyte Granulocyte Group 1: D-10 control (placebo composition) 100.0 100.0 100.0 100.0 Group 1: DO control (placebo composition) 16.5 14.3 16.7 20.9 Group 2: tetradesmus composition Ex.1a) DO (dose 50) 46.5 36.4**** 38.9** 69.8 Group 3: tetradesmus composition Ex.1a) DO (dose 100) 38.5 32.5*** 33.3* 53.5 Group 4: tetradesmus composition Ex.1a) DO (dose 250) 49.1** 44.2**** 50.0**** 55.8 Group 5: Pavlova composition Ex.1a) DO (dose 50) 60.82** 43 29**** 52.13*** 95.35*** Group 6: Pavlova composition Ex. le) D0 (dose 250) 60.54** 51.51**** 56.06**** 77.67* Group 1: control D+2 (placebo composition) 13.50 12.43 12.05 16.37 Group 2: te-tradesmus composition Ex.la) D+2 (dose 50) 40.74*** 31.14*** 31.01** 63.08*** Group 3: te-tradesmus composition Ex.la) D+2 (dose 100) 32.47** 27.41* 25.34 44.75* Group 5: Pavlova composition Ex. le) D+2 (dose 50) 13.75 11.02 9.67 20.39 Group 6: Pavlova composition Ex. le) D+2 (dose 250) 23.86 18.75 17.99 35.69

[0168] (* p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001 versus group 1 DO or group 1 D+2).

[0169] Conclusion:

[0170] Response to immunosuppression: immunosuppressive treatment decreased after 10 days (D0) the quantity of leukocytes, lymphocytes and monocytes by more than 80% and by almost 80% the quantity of granulocytes in the blood in the control group (Group 1: administration of the placebo composition - MCT oil).

[0171] The daily intake of the composition according to example 1a) (T. obliquus extract) on the other hand made it possible to limit this drastic reduction at the 3 doses studied (Groups 1, 2, 3), for lymphocytes, monocytes and granulocytes, and by at least half in the case of monocytes and granulocytes at the dose of 250 mg / kg. Lymphocytes being cells characteristic of the acquired (adaptive) immune response, and monocytes and granulocytes being characteristic of the innate immune response, the composition comprising the T. obliquus extract is effective in maintaining and increasing immune defenses, being effective on both the adaptive response and the innate response.

[0172] The composition according to example 1c) (Extract of Pavlova gyrans) also made it possible to limit even more effectively the drastic decrease in all the cell types tested observed in the control group (Group 1), with a decrease in leukocytes limited to almost 40%, a decrease in lymphocytes limited to less than 60% at most depending on the dose administered, and a decrease in monocytes limited to almost 50% compared to the control of group 1 before immunosuppression. This composition according to example 1c) (Extract of P. gyrans) proved to be particularly effective in limiting the decrease in the quantity of granulocytes in the blood in response to immunosuppression, with a decrease limited to almost 5% only and 22% only at the respective doses of 50 and 250 mg / kg in human equivalent (*** p<0.001). This composition has also been shown to be effective in limiting the decrease in the quantity of monocytes in the blood in response to immunosuppression.Monocytes being cells characteristic of the innate response, the composition according to example le) is therefore effective in strengthening the innate immune response. Similarly, by limiting the decrease in lymphocytes characteristic of the adaptive immune response, the composition according to example le) is also effective on the adaptive immune response.

[0173] Overall, the composition according to the invention is particularly effective in maintaining and increasing immune defenses, by providing a strengthening of both the innate and adaptive immune responses, whether it is the composition comprising an extract of T. obliquus or an extract of P. gyrans.

[0174] Response to P. aeruginosa infection: Infection did not decrease im- carrying the quantities of the cell types analyzed 2 days after infection in the immunocompromised control group (group 1), in comparison with the quantities measured at time 0 (DO). On the other hand, if the daily intake of the composition according to example 1c) (Extract of P. gyrans) did not strictly speaking make it possible to limit this decrease over time following infection, the composition according to example 1a) (Extract of T. obliquas) significantly maintained or almost maintained the quantities of the cell types analyzed at least two days after infection.

[0175] It is plausible that the kinetics of response to infection of the two compositions (Example 1a) and Example 1c)) were different, i.e. the response of the composition comprising the extract of Pavlova gyrans was faster than that of the composition comprising the extract of Tetradesmus obliquas, which would explain why the results in the presence of the first no longer allow the quantities of cells analyzed to be measured two days after bacterial infection: the composition comprising the extract of P. gyrans directs the immune response to the lungs. This hypothesis is also consistent with the results observed in the lungs of infected mice, in particular with regard to the effect of the composition comprising the extract of P. gyrans on the return to tissue homeostasis (Table 10, efferocytic macrophages) but also on the reduction of the bacterial load in the lungs two days after infection (Table 11).

[0176] Table 9: Measurement of the quantity of interleukins IL[3 in the blood two days after pulmonary infection by P. aeruginosa.

[0177] [Tables9] Amount of IL-1p in plasma after infection (D+2) Group 1: control D-10 (MCT placebo composition) 0 Group 1: control D+2 (MCT placebo composition) 540.95 Group 2: tetradesmus compound Ex.la) D+2 (dose 50) 40.89 Group 3: tetradesmus compound Ex.la) D+2 (dose 100) 8.72 Group 4: tetradesmus compound Ex.la) D+2 (dose 250) 9.37*

[0178] (* p<0.05 vs. Group 1)

[0179] Conclusion: the composition comprising the extract of Tetradesmus obliquus (Ex. la) has significantly decreased at the dose of 250mg / kg the amount of inflammatory interleukin 11(3) in the blood two days after infection by P. aeruginosa, unlike the composition comprising the extract of Pavlova gyrans (not shown). This result is linked to the beneficial action of the composition according to example 1a) on increasing immune defenses via its anti-inflammatory action, i.e. by reducing the amounts of one of the characteristic proinflammatory markers, interleukins 11(3).

[0180] Table 10: Mean number of immune cells (in % of living cells) measured in the lungs by flow cytometry two days after lung infection (mean % reported to the quantity of the cell type of the uninfected control group).

[0181] [TableauxlO] NKT CD4+ CD8+ Efferocytic macrophages Group 7 uninfected D+2 130.48 206.34 182.61 46.63 Group 1: placebo composition MCT D+2 100.00 100.00 100.00 100.00** (vs group 7) Group 2: te-tradesmus composition Ex.la) D+2 (dose 50) 199.83* 170.26 123.91* 112.73 Group 3: te-tradesmus composition Ex.la) D+2 (dose 100) 150.02 201.75* 132.01* 162.76 Group 4: te-tradesmus composition Ex.la) D+2 (dose 250) 131.45 246.81 129.78 144.51 Group 6: Pavlova composition Ex. le) D+2 (dose 250) 124.54 123.41 84.66 206.63**

[0182] (f T-test; (* p<0.05; ** p<0.01 vs. Group 1)

[0183] P. aeruginosa infection induced a decrease in the amount of NKT lymphocytes and CD4 and CD8 T lymphocytes in placebo group 1 (Composition comprising MCT oil). On the contrary, pulmonary infection tended to increase the amount of efferocytic macrophages in group 1 compared to the uninfected control group.

[0184] The composition according to Example 1a) comprising a T. obliquus extract limited the decrease in CD8 T lymphocytes at the doses administered, and tended to limit the decrease or tended to almost maintain the quantity of CD4 T lymphocytes in the lungs of the mice. The T. obliquus extract and the composition comprising it are effective in both maintaining and increasing the cell types involved in the adaptive immune response.

[0185] The composition according to example 1c) comprising an extract of P. gyrans tended to increase the quantity of efferocytic macrophages up to 4 times the quantity detected in the uninfected control group. This result associated with the maintenance of the quantity of monocytes in the blood in response to treatment with cyclophosphamide (DO) by this same composition (Table 8) demonstrates that the extract of P. gyrans and the composition according to the invention comprising it are therefore particularly effective in accelerating the return to tissue homeostasis during the immune response, the return to tissue homeostasis corresponding to the last stage of the immune response.

[0186] Table 11: Measurement of bacterial load in the lungs at time D+2 after infection by P. aeruginosa.

[0187] [Tables] MOY (Logio of CFU (mL)) Standard deviation Group 1: control D+2 (MCT placebo composition) 6.3 0.4 Group 2: tetra composition Ex.la) D+2 (dose 50) 6.4 0.3 Group 3: tetra composition Ex.la) D+2 (dose 100) 5.2 0.2 Group 4: tetra composition Ex.la) D+2 (dose 250) 4.3 0.2 Group 5: Pavlo composition Ex. le) D+2 (dose 50) 4.3 0.2 Group 6: Pavlo composition Ex. le) D+2 (dose 250) 2 3*** 0.5

[0188] (*** p<0.001 vs. Group 1)

[0189] Conclusion: The composition according to example 1c) comprising an extract of Pavlova gyrans significantly reduced the bacterial load 2 days after infection with P. aeruginosa in comparison with the bacterial load measured in the lungs of mice in the infected control group having received the placebo composition.

[0190] Table 12: Measurement of mouse weight (average % of weight at time D x by relative to initial weight at time D-10) (n=6).

[0191] [Tables 12] D-9 D-8 D-7 D-6 D-5 D-4 D-3 D-2 Dl D0 D+l D+2 Group 7 (uninfected) 1.4 3.4 4.9 4.6 3.9 5.0 4.9 4.5 4.5 4.1 3.5 4.2 Group 1: control D+2 (MCT placebo composition) 0.3 1.7 1.3 3.3 3.3 4.2 3.3 1.9 -1.0 -2.0 -5.3 -9.2 Group 3: tetradesmus composition Ex.la) dose 100 D+2 2.7 4.1 3.8 5.7 3.0 3.4 2.5 2.2 1.3 1.4 -0.7 -0.6 Group 4: tetradesmus composition Ex.la) dose 250 D+2 2.3 3.5 4.5 5.9 3.7 5.1 4.0 3.2 2.4 1.7 -0.8 -2.2 Group 5 Pavlova Example 1) dose 100 2.4 2.5 2.5 3.4 2.4 4.9 3.3 1.7 0.4 1.6 0.1 -1.3 Group 6: composition Pavlova Example 1) dose 250 D+2 2.0 2.0 6.0 7.0 4.4 5.8 4.4 3.2 1.7 1.8 -0.5 -0.8

[0192] Conclusion: The weight of mice in the control group not infected with P. aeruginosa increased during the trial. In contrast, mice in the infected control group receiving a placebo composition (MCT oil) saw their weight decrease to more than 9% at time D+2, i.e. 2 days after pulmonary infection by the bacteria. Daily administration of the composition comprising an extract of T. obliquas (groups 2 and 3) (Example 1a) or comprising an extract of P.gyrans (groups 4 to 6) (Example 1c) made it possible to maintain the initial weight of the mice at the start of the preclinical trial, with a percentage change in weight of -0.6% to a maximum of 2.2%. The composition according to the invention, whether it comprises an extract of T. obliquus or an extract of P. gyrans, is particularly effective in countering weight loss due to infection by P. syringae. Example 3b) Effect on immunity in humans:

[0193] In the context of the clinical trial described in Example 2c), a blood sample was taken from each participant and a blood measurement of the following cytokines or markers of inflammation was taken: GM-CSF, IFNy, IL-1a, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, and TNF-a at time 0 (Initial recruitment visit), 2 weeks before the start of the trial, on the day of the start of the clinical trial and 2 weeks and 4 weeks after the start of the trial.

[0194] Example 4: Effect of the composition according to the invention on stress

[0195] As part of the clinical trial described in Example 2c), saliva samples were collected from each participant. A dosage of α-amylase (sAA), chromogranin A (CgA) and lysozyme was performed from these saliva samples. Similarly, a blood sample was taken to measure the amounts of blood-derived neurotrophic factor (BDNF), adrenocorticotropic hormone (ACTH) and cortisol. The blood and saliva samples were taken at time 0 (Initial recruitment visit), 2 weeks before the start of the trial, on the day the clinical trial started and 2 weeks and 4 weeks after the start of the trial.

Claims

Claims

1. Oral or sublingual composition comprising an extract of Tetradesmus sp. and / or an extract of Pavlova sp., and at least one nutraceutical acceptable excipient.

2. Composition according to claim 1, characterized in that the nutraceutically acceptable excipient is chosen from carrier agents, bulking agents, preservatives, acidifying agents, emulsifying agents, humectants, gelling agents, lubricating agents, coating or encapsulating agents, stabilizing or dispersing agents, sweetening agents, and mixtures thereof.

3. Composition according to any one of claims 1 or 2, further comprising at least one vegetable oil and vitamin E, advantageously α-tocopherol.

4. Composition according to claim 3, characterized in that the vegetable oil is an oil with medium-chain triglycerides, advantageously coconut oil.

5. Composition according to any one of claims 1 to 4, characterized in that the weight ratio of Tetradesmus sp. extract and Pavlova sp. extract ranges from 100 / 0 to 0 / 100, advantageously from 75 / 25 to 25 / 75, inclusive 50 / 50, and advantageously again it is 75 / 25.

6. Composition according to any one of claims 1 to 4, characterized in that it comprises by final weight relative to the total weight of the composition: - a content of Tetradesmus sp. extract ranging from 8% to 79.85%, advantageously ranging from 20% to 50%, still advantageously from 20% to 30% and very advantageously 29%; - a coconut oil content ranging from 20% to 90%, advantageously ranging from 60% to 90%; - an α-tocopherol content ranging from 0.15% to 1.25%, advantageously from 0.25% to 1%, very advantageously 0.5%.

7. Composition according to any one of claims 1 to 5, characterized in that it comprises in final weight relative to the total weight of the composition: - A content of Tetradesmus sp. extract ranging from 4% to 40%, advantageously ranging from 10% to 25%, very advantageously 21.75%; - A content of Pavlova sp. extract ranging from 4 to 40%, advantageously ranging from 10% to 25%, still advantageously from 10% to 15% and very advantageously 7.25%; - A coconut oil content ranging from 20% to 90%, advantageously ranging from 60% to 90%; - An a-tocopherol content ranging from 0.15% to 1.25%, advantageously from 0.25% to 1%, very advantageously 0.5%.

8. Composition according to any one of claims 1 to 7, characterized in that the Tetradesmus sp. extract and / or the Pavlova sp. extract is an extract obtained by solid-liquid extraction in a solvent or solvent mixture chosen from water, acetone, hexane, ethyl acetate, methyltetrahydrofuran, 2-methyloxolane, heptane, an alcohol chosen from ethanol, methanol or isopropanol, a natural or branched oil, a glycol, a polyol and a water / alcohol or water / glycol mixture in a proportion of 99 / 1 to 1 / 99 (w / w), or an extract obtained by supercritical CO2 extraction.

9. Composition according to any one of claims 1 to 8, characterized in that the extract of Tetradesmus sp. and / or the extract of Pavlova sp. is obtained by extraction in ethanol as the sole solvent.

10. Composition according to any one of claims 1 to 9, characterized in that the extract of Tetradesmus sp. is an extract of Tetradesmus obliquus.

11. Composition according to any one of claims 1 to 10, characterized in that the extract of Pavlova sp. is an extract of Pavlova gyrans.

12. Composition according to any one of claims 1 to 11, in the form of a food supplement.

13. Composition according to any one of claims 1 to 12, in the form of a capsule, gel cap, tablet, tablet, candy, chewing gum, orodispersible tablet or sublingual tablet, orodis-persible granule or sublingual granule, pill, orodispersible lozenge or sublingual lozenge, energy bar, kibble, pâté, treat, granules, soft capsule, syrup, spray, ampoule, suspension, emulsion, hot or cold drink.

14. Composition according to any one of claims 1 to 13, characterized in that it is in the form of oil or in the form of powder.

15. Composition according to any one of claims 1 to 14, characterized in that it comprises a final quantity of lutein by weight relative to the total weight of the composition less than or equal to 1%, preferably less than or equal to 0.5%.

16. Composition according to any one of claims 1 to 15, for use as a medicament.

17. Composition according to any one of claims 1 to 15, or extract of Tetradesmus sp. as described in any one of claims 8 to 10, for its use for: - reducing intestinal hyperpermeability and / or - strengthening the intestinal barrier and / or - improving intestinal transit and / or - preventing and / or improving gastrointestinal disorders, advantageously those generated by intestinal hyperpermeability and / or - maintaining and / or increasing immune defenses and / or - reducing stress, advantageously stress induced by intestinal discomfort and / or chronic stress generating intestinal discomfort.

18. Composition or extract of Tetradesmus sp., for its use according to claim 17 for improving intestinal comfort, well-being, sleep and / or cognitive abilities.

19. Composition according to any one of claims 1 to 18, characterized in that it is intended for animals, advantageously for humans, in particular for humans practicing a high-intensity sporting activity.

20. Composition according to any one of claims 1 to 15 or extract of Pavlova sp. as defined in any one of claims 8 to 11, for its use in maintaining and / or increasing immune defenses by accelerating the return to tissue homeostasis during the immune response.

21. A composition for use according to claim 20 for providing a complete immune response.