Novel dietary supplement composition and uses thereof

A composition of Tetradesmus sp. and/or Pavlova sp. microalga extracts addresses the challenges of intestinal hyperpermeability and gastrointestinal disorders by reducing adverse effects, improving intestinal health, and enhancing immune defenses.

WO2025133482A1PCT designated stage expired Publication Date: 2025-06-26MICROPHYT
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Patent Information

Application Number
PCT/FR2024/051411
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-01-25
Filing Date
2024-10-25
Publication Date
2025-06-26

AI Technical Summary

Technical Problem

Current solutions for modulating intestinal microbiota to address intestinal hyperpermeability often cause gastrointestinal disorders and other adverse effects, necessitating the development of alternative ingredients that are effective without these disadvantages.

Method used

A composition comprising an extract of the microalga Tetradesmus sp. and/or Pavlova sp., combined with nutraceutically acceptable excipients, is used orally or sublingually to reduce intestinal hyperpermeability, improve intestinal transit, and prevent gastrointestinal disorders, while maintaining and increasing immune defenses.

Benefits of technology

The composition effectively reduces intestinal hyperpermeability, improves intestinal transit, prevents gastrointestinal disorders, and enhances immune defenses, offering a natural and safe alternative to existing solutions.

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Abstract

The invention relates to a novel 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 medicine, in particular for reducing intestinal hyperpermeability, and / or reinforcing the intestinal barrier, and / or improving intestinal transit, and / or modulating intestinal microbiota and / or improving gastrointestinal disorders, and / or maintaining and / or increasing immune defences and / or reducing stress. The composition improves well-being, sleep and cognitive abilities, in particular in humans.
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Description

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 intolerances such as gluten intolerance, milk protein intolerance, or diseases such as celiac disease. Intensive exercise 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 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 nutraceutical field offers numerous solutions for modulating the intestinal microbiota, starting with the use of probiotics with the aim of regulating intestinal health, particularly 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 previously mentioned disadvantages.

[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] The microalgae of the genus Tetradesmus, belonging to the Scenedesmaceae family, include more than ten distinct species. These include the species Tetradesmus obliquus. 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 microalga 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 for promoting cell growth, collagen synthesis, increasing skin elasticity and improving pigmentation. In one embodiment, it is an extract of the strain S. obliquus. This composition is only 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] Cabrita et al. (2023) described a clinical study in dogs consisting of supplementing their daily ration with the whole microalga of Tetradesmus obliquus, measuring acceptability by dogs, digestibility and measuring certain fecal parameters after oral administration. However, the described composition incorporating the microalga T. obliquus is not a composition comprising an extract of the microalga T. obliquus, since no extract of this microalga is ever described. Indeed, only the biomass is ingested by dogs. However, such biomass is different from an extract since in particular it contains much more protein. Furthermore, this publication does not disclose a use of a composition comprising an extract of T.obliquus to reduce intestinal hyperpermeability and / or strengthen the intestinal barrier and / or improve intestinal transit; and / or to prevent and / or improve gastrointestinal disorders; and / or to modulate the intestinal microbiota. In this respect, concerning the modulation of the intestinal microbiota, this document describes page 10, 2 èmecolumn, last paragraph that the administration of the described composition containing the microalga T. obliquus induces a decrease in the Shannon index, characteristic of microbial diversity (Alpha-diversity). However, it is an increase in this index that would show an increase in microbial diversity that is logically expected if the microalga had a modulating effect on the intestinal microbiota. In addition, this document describes on page 11, first column and figure 4 a decrease in the quantity of bacteria of the genus Lactobacillus in the intestinal microbiota of the dog for a composition including the microalga T. obliquus. This same figure 4 shows no effect detected for bacteria of the genus Bifidobacterium with this same composition. However, these 2 genera are known to be particularly beneficial in dogs.More generally, this document only shows a decrease in the fecal score and a slight decrease in the number of defecations per day, which does not predict an improvement in intestinal hyperpermeability, nor a strengthening of the intestinal barrier. Fecal production also remains unchanged in the presence of the microalgae T. obliquus and not significantly different from the control. Thus, in the context of oral administration in dogs, and more generally in mammals, in. especially domestic animals, this composition is not beneficial and there is no incentive to use it especially in domestic animals suffering from intestinal dysfunction or discomfort. This is even more true for an extract containing a protein content much lower than biomass since this article teaches the interest of finding new sources of useful proteins in dogs as indicated on page 13, first column, first paragraph.

[0011] Finally, at no point does this document describe or suggest that the results are transposable to humans. The daily ration administered to dogs and including the dried microalgae of T. obliquus is of the order of 278 g per day (Table 6). However, the composition including said algae comprises 25.4% of proteins (Table 1), i.e. a daily intake for dogs of 70.6 g / day of proteins for an average weight of 12.6 kg, which therefore makes 5.60 g / kg dog / day of proteins. In human equivalent and taking into account the conversion factor to be applied to the human dose (FDA Food and Drug Administration; Guidelines “Estimating the Safe Starting Dose in Clinical Trials for Therapeutics in Adult Healthy Volunteers”), this would correspond to 2.85g / kg human / day of protein, or approximately 200g / day of protein for a 70kg human, which is 4 times higher on average (male / female) than the recommended dose in humans (EU EFSA Recommendations, Dietary Reference Values).The same is true for the daily carbohydrate intake of 85.52g / day in a dog weighing 12.6kg on average, taking into account the same daily ration of 278g (Table 6) and the average carbohydrate content of 30.7% of the administered ration (Table 1), i.e. 6.78g lipids / day / kg dog. In human equivalent, this is equivalent to 3.67g / kg human / day, i.e. 257g of carbohydrates / day in a 70kg human, which is twice the recommended daily intake.

[0012] In fact, it is clear that the composition comprising the whole microalgae T. obliquus described in this document, which is in fact studied as an alternative source of protein for dog food, is not at all suitable for administration in humans.

[0013] Similarly, Kim et al. (2023) described the effects of the microalgae Chlorella vulgaris and T. obliquus via oral administration in hens, concluding that there was an effect on egg color but no effect on markers of immunity or modulation of the amount of short-chain fatty acids could be demonstrated. The composition described does not mention the incorporation of any T. obliquus extract. Furthermore, at no point does this document describe or suggest that the results are transposable to humans.

[0014] Finally, 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.

[0015] 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

[0016] 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.

[0017] 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, in particular uncomfortable gastrointestinal disorders; and / or in modulating the intestinal microbiota and / or maintaining and / or increasing immune defenses; and / or in 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.

[0018] The invention therefore relates primarily to an oral or sublingual composition comprising an extract of Tetradesmus sp., advantageously T. obliquus, and / or an extract of Pavlova sp., advantageously P. gyrans, and at least one nutraceutically acceptable excipient.

[0019] 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. EXTRACT

[0020] For the purposes of the present invention, the term "Tetradesmus sp." extract or "Pavlova sp." extract means 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 term "T. obliquus extract" therefore means indifferently "T. obliquus extract" or "Scenedesmus obliquus extract".

[0021] 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.

[0022] 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 cultivation of microalgae is carried out according to the batch, fed-batch, continuous, semi-continuous, turbidostat or chemostat culture management methods.

[0023] The extraction can be carried out from frozen or fresh biomass of T. obliquus 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.

[0024] The biomass can be centrifuged and then filtered to remove 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 according to the invention is lipophilic, in particular oily.

[0025] 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 preferably 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.

[0026] In another 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 even 120°C, 145°C then 170°C.

[0027] 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 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.

[0028] 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.

[0029] 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.

[0030] In all cases, the T. obliquus 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.

[0031] Thus, in a first advantageous embodiment of the invention, the extract of T. obliquus is obtained as follows: a quantity of 100g of dried and filtered biomass of T. obliquus 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).

[0032] In a second advantageous embodiment of the invention, a crude oily extract of T. obliquus 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).

[0033] In a 3 èmeembodiment, 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).

[0034] The liquid extract of T. obliquus 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).

[0035] In another embodiment, the two liquid extracts of T. obliquus 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 two liquid extracts of T. obliquus 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 1d).

[0036] Alternatively, the liquid (oily) extract of T. obliquus 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 1e).

[0037] In a particularly advantageous embodiment of the invention, the extract of Tetradesmus sp., advantageously of T. obliquus, comprises a so-called non-significant quantity of lutein, 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.

[0038] In yet another particularly advantageous embodiment of the invention, the extract of Tetradesmus sp., advantageously of T. obliquus, comprises a quantity of total proteins of less than 70%, preferably less than 40%, even more preferably less than 30%, in particular less than 20% and very preferably less than 10%, by weight relative to the total weight of the extract. COMPOSITION

[0039] 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. In particular, it may comprise an extract of Tetradesmus sp. alone, without extract of Pavlova sp.

[0040] The composition according to the invention comprises a weight ratio of the extract of T etradesmus 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 or 100 / 0.

[0041] 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, 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 locust bean gum.The preservatives are chosen from sodium sorbate or sodium benzoate; the acidifying agents are chosen in particular from citric acid or sodium citrate; the emulsifying agents are chosen from lecithin, phospholipids, polyethylene glycols; the humectants are chosen from glycerin, sorbitol, dextrose. As bulking agents, mention may be made of mannitol, lactose, sorbitol, starch, microcellulose, hydroxypropylmethylcellulose, crosscarmelose, polyvinylpyrrolidone, calcium phosphate (di and tribasic). anhydrous or hydrated), citric acid or tartaric acid, sodium or potassium or calcium carbonates, siliceous cellulose, or acacia gum. Lubricating agents (anticaking agents) include magnesium stearate, stearic acid, lecithins, colloidal silica, rice extract, talc, glycerol dibehenate, or bamboo extract titrated in silica. Coating or encapsulating agents may be chosen from gelatin, hydroxypropylmethylcellulose, pululan, beeswax or carnauba wax. Gelling agents may be chosen from starches, native or pregelatinized, carrageenans, pectin, alginates, agar-agar, xanthan gum or gelatin. Examples of stabilizing or dispersing agents include alginates, acacia gum and phospholipids.Finally, sweetening agents include maltitol, xylitol, sucralose, sorbitol, agave syrup, glucose syrup, sucrose, fructose, stevia extract, honey, isomalt, or maltitol.

[0042] Advantageously, the excipient is intended for oral administration in animals, including humans, more particularly humans aged over 4 years, more advantageously in mammals, including humans, even more advantageously in domestic animals, in particular domestic mammals. In a particularly advantageous embodiment, the excipient is intended for oral administration in humans, more particularly in humans aged over 4 years.

[0043] 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%.

[0044] 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 can thus be chosen from coconut oil, advantageously coconut oil, palm kernel oil and palm oil, but can be obtained from other fats or oils. Advantageously within the meaning of the invention, the vegetable oil is an MCT oil, advantageously still 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%, advantageously still 60% to 90%, including between 70% and 80% and even advantageously 70.5%.

[0045] In an advantageous embodiment, the excipient according to the invention comprises, in particular consists of, vegetable oil as described above.

[0046] 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, 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%.

[0047] 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. obliquus, still advantageously of T. obliquus extract obtained in ethanol as 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%.

[0048] 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, in particular uncomfortable gastrointestinal disorders, and / or modulating the intestinal microbiota, 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. In particular, this use is in humans, more particularly those aged over 4 years.

[0049] Alternatively and advantageously for the above uses, the composition according to the invention comprises 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 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 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%.

[0050] Alternatively, the composition according to the invention comprises a weight ratio of Tetradesmus sp. extract, advantageously T. obliquus, and Pavlova sp. extract, advantageously P. gyrans, of 75 / 25. The composition according to the invention may thus comprise 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 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%; - A content of α-tocopherol ranging from 0.15% to 1.25%, advantageously from 0.25% to 1%, very advantageously 0.5%.

[0051] This composition is advantageously intended for use in maintaining and / or increasing immune defenses, advantageously in humans, in particular those aged over 4 years.

[0052] Alternatively, a composition advantageously intended for use in maintaining and / or increasing immune defenses, advantageously in humans, in particular aged over 4 years, comprises by 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 0.5%.

[0053] Still alternatively and advantageously for its use in maintaining and / or increasing the immune defenses, advantageously of humans, in particular aged over 4 years, very advantageously in 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%; - A α-tocopherol content ranging from 0.15% to 1.25%, advantageously from 0.25% to 1%, very advantageously 0.5%.

[0054] In a particularly advantageous embodiment of the invention, the composition comprises a non-significant quantity of lutein, whereby "non-significant quantity" is understood here within the meaning of the present invention to mean a final quantity by weight relative to the total weight of the composition of 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, but is still advantageously responsible for the effect of increasing immune defenses.

[0055] In yet another particularly advantageous embodiment of the invention, the composition comprises a quantity of total proteins of less than 20%, preferably less than 10% and even more preferably less than 5%, by weight relative to the total weight of the composition.

[0056] The composition according to the invention may also comprise any compound active on the intestinal microbiota. In this respect, mention may be made of carotenoids, in particular lycopene, zeaxanthin, meso-zeaxanthin, astaxanthin, cryptoxanthin, flavoxanthin, neoxanthin, other α or β carotenes, or fucoxanthin. Similarly, mention may 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 C 11 -C 26 .

[0057] The composition may also include omega-3 polyunsaturated fatty acids such as docosahexaenoic acid, docosapentaenoic acid, eicosatetraenoic acid, hexadecatrienoic acid, eicosapentaenoic acid, α-linolenic acid, stearidonic acid, eicosatrienoic acid, heneicosapentaenoic 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 C 20 H 30 O2), docosahexaenoic acid (DHA; cas number 6217-54-5; molar mass 328.48g / mol; empirical formula C 22 H 32 O2) or their mixture.

[0058] 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 extract of T.obliquus. The composition will advantageously comprise in this case a lipid extract chosen from a lipid extract of Phaeodactylum tricornutum known for its significant quantity of EPA and / or a lipid extract of Haematococcus pluvialis, which also comprises astaxanthin, and / or a lipid extract of Pavlova gyrans or Pavlova lutheri.

[0059] As part of a complementary effect of prevention or treatment of intestinal dysbiosis and / or intestinal imbalance, the composition according to the invention can be associated with dietary fibers such as cellulose, hemicellulose, starch, pectins, β-glucans.

[0060] 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, orodispersible 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.

[0061] 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 weight relative to the total weight of the powder, by any known technique of the person skilled in the art such as atomization, or by fluidized bed coupled with microencapsulation via a support matrix.

[0062] 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.

[0063] It is advantageously packaged in doses having a unit weight of between 50mg and 2g, advantageously between 100mg and 500mg, very advantageously between 100mg and 250mg.

[0064] 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.

[0065] The composition according to the invention and the uses according to the invention, in particular as described above, are intended for animals, it being understood according to the invention by "animals" mammals, more particularly humans, in particular aged over 4 years, domestic animals chosen from dogs and cats, and horses, cows, pigs, pigs, preferentially domestic animals and humans, in particular aged over 4 years, even more preferentially humans, in particular aged over 4 years.In a first advantageous embodiment of the invention, the composition according to the invention is intended for domestic animals, in particular domestic mammals, advantageously domestic animals (in particular domestic mammals) exhibiting intestinal dysbiosis and / or suffering from intestinal discomfort, advantageously also elderly domestic animals (in particular domestic mammals), "elderly domestic animals" being understood to mean domestic animals. aged over 7 years and by “old domestic mammals” domestic mammals aged over 7 years.

[0066] In a second advantageous embodiment, the composition and uses according to the invention are intended for humans, in particular those aged over 4 years. In a particular embodiment of the invention, the composition according to the invention is not intended for young children aged under 4 years, advantageously under 3 years and very advantageously under 2 years. Even more particularly, the composition according to the invention is not intended for newborns.

[0067] In particular, the composition and uses according to the invention are intended for humans suffering from intestinal discomfort and / or exhibiting intestinal dysfunction. Alternatively, the composition and uses according to the invention are intended for humans exhibiting weakened immune defenses, advantageously due to external and / or internal stress.

[0068] In another particular embodiment, the composition according to and the uses of the invention are intended for humans practicing a high-intensity sporting activity.

[0069] Thus, advantageously, the composition according to the invention is administered at a daily dose in human equivalent (for a human of average weight of 70kg) of 20 to 1000mg, advantageously from 50 to 750mg, advantageously again from 50 to 520mg, and very advantageously from 50 to 250mg, inclusive 100mg and 150mg, 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.

[0070] In a particular embodiment of the invention, when the composition according to the invention comprises both an extract of Tetradesmus sp., advantageously of T. obliquus, still advantageously of an extract of T. obliquus 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 750mg, very advantageously from 100mg to 520mg, including 200mg.

[0071] When the composition and uses are intended for animals other than humans, particularly when it is intended for domestic animals, in particular domestic mammals, advantageously dogs, it is advantageously packaged in the form of granules, pâté, treats, kibble and comes as a supplement to a balanced daily ration, that is to say reaching the recommended daily doses for dogs, in particular in proteins and lipids. In this case, the daily dose ranges from 1 to 460 mg, advantageously from 3.5 to 300 mg, advantageously from 3.5 to 180 mg, including 25, 33, 50 and 100 mg. The daily dose of lutein administered in this case therefore ranges from 0.0003mg to 1.38mg, advantageously from 0.0105mg to 0.9mg, and even more advantageously from 0.0105mg to 0.45mg, including 0.075, 0.15 and 0.3mg.

[0072] The composition according to the invention is advantageously administered for a period ranging from 1 week to 6 weeks, advantageously from 1 week to 4 weeks. When the composition and the uses are intended for animals other than humans and advantageously for domestic animals, in particular domestic mammals, still advantageously for dogs, it is administered for a period ranging from 2 weeks to 6 weeks and advantageously from 2 weeks to 4 weeks. USES

[0073] Another subject of the invention therefore relates to the composition according to the invention for its use as a medicament, advantageously intended for humans, in particular aged over 4 years.

[0074] 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, advantageously in humans, in particular aged over 4 years, for - reducing intestinal hyperpermeability, advantageously in humans, in particular aged over 4 years, and / or - strengthen the intestinal barrier, advantageously in humans, in particular aged over 4 years and / or - improve intestinal transit, advantageously in humans, in particular aged over 4 years, and / or - prevent and / or improve gastrointestinal disorders, in particular uncomfortable gastrointestinal disorders, advantageously in humans, in particular aged over 4 years, advantageously those generated by intestinal hyperpermeability, advantageously in humans, in particular aged over 4 years, and / or - modulate the intestinal microbiota, advantageously in humans, in particular aged over 4 years, and / or - maintain and / or increase immune defenses, advantageously in humans, in particular aged over 4 years, and / or - accelerate the return to tissue homeostasis during the immune response, advantageously in humans, in particular aged over 4 years, and / or - reduce stress, advantageously in humans,in particular aged over 4 years, advantageously stress induced by intestinal discomfort and / or chronic stress generating intestinal discomfort.

[0075] 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 abilities, advantageously in animals, particularly domestic mammals, and very advantageously in humans, in particular those aged over 4 years.

[0076] 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 for maintaining and / or increasing the immune defenses, advantageously of humans, in particular aged over 4 years, advantageously by accelerating the return to tissue homeostasis during the immune response, and advantageously providing a complete immune response advantageously in a human, in particular aged over 4 years.

[0077] For the purposes of the invention, the expression "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 pre-clinical test carried out in mice 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.

[0078] 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 colon fragments observed, for example, in the mice of the pre-clinical trial of example 2a) in response to inflammation generated by SSD and. Advantageously in this case, since SSD reduces the average length of 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).

[0079] For the purposes of the present invention, the expression "strengthening the intestinal barrier" also means improving the intestinal microbiota. In one embodiment of the invention, this involves modulation of the intestinal microbiota. "Modulation of the intestinal microbiota" means an increase in microbial diversity, advantageously microbial diversity at the taxon level.

[0080] Advantageously, the modulation of the intestinal microbiota is evaluated by genomics and measurement of the so-called Shannon index (“Alpha-diversity index”) following the 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, it is the composition comprising an extract of T. obliquus, advantageously that described in example 1a). The results are presented in example 2c).

[0081] The composition comprising the T. obliquus extract according to the invention is therefore effective and can be used to modulate the intestinal microbiota, advantageously of humans, in particular those aged over 4 years. In particular, the composition is not intended for young children aged under 4 years, advantageously under 3 years and even more advantageously under 2 years.

[0082] In an alternative embodiment of the invention, “modulating the intestinal microbiota” means increasing the detected quantity of bacterial genera having a positive impact in particular on strengthening the intestinal barrier in the presence of the composition according to the invention. Advantageously, the genera are in particular chosen from the genera Lactobacillus and Bifidobacterium. In an advantageous embodiment, this increase is measured in the context of a pre-clinical study in mice, after administration of the composition according to the invention.

[0083] Furthermore, within the meaning of the present invention, the expression "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 mice (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.

[0084] In an alternative embodiment of the invention, it is understood within the meaning of the invention by "strengthening the intestinal barrier" and / or "improving intestinal transit", advantageously in humans, in particular aged over 4 years, to modulate the quantity produced of short-chain fatty acids (SCFA) chosen from propionate (C3H6O2, molar mass 74.08 g / mol, CAS No. 79-09-4), acetate (C2H4O2, molar mass 60.05 g / mol, CAS No. 71-50-1) and butyrate (C4H8O 2, molar mass 88.11 g / mol, CAS n°107-92-6), preferably butyrate, and / or improve the intestinal absorption of short-chain fatty acids (SCFAs) selected from propionate, acetate and butyrate, and advantageously butyrate. Also advantageously, this is an improvement in the intestinal absorption of butyrate. Advantageously in this case, the improvement in the absorption of butyrate is measured by measuring the amount of butyrate in the stool, for example in the context of the clinical trial described in example 2c).

[0085] Thus advantageously the composition according to the invention is for its use to improve intestinal transit, advantageously of humans, in particular aged over 4 years, by modulating the quantity of butyrate produced, and / or by improving the intestinal absorption of butyrate.

[0086] For the purposes of the present invention, the expression "preventing and / or improving gastrointestinal disorders", advantageously in humans, in particular aged over 4 years, is also understood to mean improving at least one of the disorders, advantageously in humans, in particular aged over 4 years, chosen from diarrhea and / or constipation and / or colitis and / or bloating and / or gas and / or intestinal discomfort due to digestion and / or inflammation of the colon and / or intestinal dysfunction and / or intestinal pain and / or fatigue and / or weight loss. The composition according to the invention is in fact effective in significantly reducing the scores of the so-called GSRS (Gastrointestinal Symptom Rating Scale) questionnaire implemented within the framework of the clinical study as described in example 2c).

[0087] By strengthening the intestinal barrier, reducing intestinal hyperpermeability and preventing or improving gastrointestinal disorders, the composition according to the invention improves intestinal comfort, advantageously in animals, and even more advantageously in humans, in particular those over 4 years old.

[0088] Furthermore, 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 immune response and adaptive. "External stress" here means, but is not limited to, stress such as intense physical activity, taking medication, or a benign pathology other than cancer or an autoimmune disease. "Internal stress" here means, but is not limited to, a dietary imbalance, hormonal changes, stress, or anxiety.

[0089] In a first embodiment, it is a question of maintaining the detected quantity of cells chosen from leukocytes and / or lymphocytes and / or monocytes and / or neutrophil granulocytes of at least 30%, advantageously of at least 40% and very advantageously of at least 50% in the presence of the composition according to the invention in comparison with the detected quantity of the same cells without composition according to the invention, also subjected to immunodepression. Still advantageously, it is a question of maintaining the quantity of said cells measured in the plasma of a population of mice 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. obliquus, 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 11). Each of these two compositions is therefore effective on both the adaptive and innate immune response.

[0090] Furthermore, within the meaning of the present invention, the term "increasing immune defenses" means reducing inflammation by reducing the quantity in the blood of at least one pro-inflammatory marker chosen from interleukins IL1β, IL6, TNFα (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.

[0091] In one embodiment of the invention, the decrease in the quantity of at least one pro-inflammatory blood marker is measured in the context of the pre-clinical test in mice as detailed in example 3a) in the presence of the composition according to the invention comprising an extract of T. obliquus. Advantageously in this case, it is the reduction in the quantity of blood interleukin IL1β measured two days after pulmonary infection by the bacterium Pseudomonas aeruginosa in the presence of the composition according to example 1a) (Table 12).

[0092] 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 mouse population of the preclinical trial detailed in Example 3a), in the presence of the composition according to the invention comprising a T extract.obliquus, advantageously still the composition of example 1a) (Table 13), in comparison with the measured quantities of the same cells in the lungs of the groups of mice having received the placebo composition (Group 1) (i.e. without composition according to the invention).

[0093] In yet another embodiment of the invention, "increasing immune defenses" is understood to mean accelerating the return to tissue homeostasis during the immune response.

[0094] "Accelerating 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, "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 mice infected with the bacteria Pseudomonas syringae, as detailed in Example 3a) (Table 13) 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 mice having received the placebo composition (Group 1). Very advantageously, the increase in the quantity of efferocytic macrophages is measured 2 days after pulmonary infection by P. aeruginosa in the presence of the composition comprising an extract of P. gyrans, advantageously the composition according to Example 1c).

[0095] 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 14).

[0096] The composition according to the invention comprising both an extract of Tetradesmus sp., advantageously T. obliquus, 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.

[0097] 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.

[0098] Furthermore, for the purposes of the present invention, the term "reducing stress", advantageously in humans, in particular those aged over 4 years, 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, and advantageously chromogranin A, measured within a population of individuals in the context of the clinical trial described in example 2c) in response to 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).

[0099] By reducing stress, the composition according to the invention and the extract of T. obliquus, is also useful for improving well-being or indifferently within the meaning of the invention mood, but also sleep, advantageously in humans, in particular aged over 4 years. Here, by "improving mood" is meant reducing the score of negative affects via the questionnaire known as PANAS (Positive and Negative Affect Schedule) (Watson et al., 1988) after 4 weeks of administration of the composition according to the invention, advantageously according to the composition according to example 1a), in the context of the clinical study described in example 2c) (Example 5).

[0100] 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 quantity of C-reactive protein (C-reactive Protein hs-CRP) and / or the quantity of tumor necrosis factor alpha (TNFα) in the blood and / or the cerebral cortex. C-reactive protein is a predictive marker of cognitive functions and a Elevated levels of this protein are a sign of dementia in healthy middle- to older-aged human populations. Interleukin-6 is a mediator of C-reactive protein synthesis. TNFα is a proinflammatory cytokine with a role in cerebral cortex inflammation.

[0101] 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 mice 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 mice as well as inflammation resulting in an increase in TNFα 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. obliquus, still advantageously the composition according to example 1a). Very advantageously, the quantity of TNFα and IL-6 are evaluated by ELISA immunoassay.

[0102] In another embodiment of the invention, the effect of the composition according to the invention on cognitive abilities is evaluated in vivo in the context of a pre-clinical study in mice consisting of the daily oral administration of the composition according to the invention, advantageously the composition according to example 1a), or of a placebo composition, for a period of 10 weeks, to a population of mice subjected to injections of lipopolysaccharides inducing low-grade inflammation in the cortex of the mice. The effectiveness of the composition according to the invention in comparison with the placebo composition is studied via behavioral tests in the population of mice such as for example the Barnes Maze test evaluating spatial learning and memory or the Y-Maze test evaluating spatial working memory.

[0103] In yet 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 administration by oral route 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 assessed through 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.; Kappelle, LJ; de Haan, EH F (2000). "The Corsi Block-Tapping Task: Standardization and Normative Data". Applied Neuropsychology.57 (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 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 cognitive and perceptual abilities assessed by the Neurotracker light reaction test.

[0104] Due to its effect of modulating the intestinal microbiota, the composition comprising the T. obliquus extract is therefore effective in improving cognitive functions, advantageously in humans, particularly those aged over 4 years. It is indeed known that the intestinal microbiota has an impact on cognitive functions in humans and animals (“Gut-Brain Axis”) (Fekete et al., 2024).

[0105] Associated with the effects of strengthening the intestinal barrier and reducing intestinal hyperpermeability in particular, the composition according to the invention by its effect on strengthening immune defenses, constitutes a complete food supplement allowing 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, advantageously of humans, in particular aged over 4 years.

[0106] Another subject matter 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, and / or modulating the intestinal microbiota, comprising administering orally or sublingually to a patient in need thereof 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, in particular aged over 4 years.

[0107] The method is thus effective in improving well-being or, indifferently within the meaning of the invention, mood, intestinal comfort, sleep and / or cognitive abilities, advantageously of animals, in particular mammals, still advantageously of humans, in particular aged over 4 years, but also in providing a complete immune response.

[0108] In an advantageous embodiment of the invention, the method of the invention comprises the steps of: - Selecting an animal, in particular a mammal, advantageously a human, in particular aged over 4 years, 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 discomfort due to digestion and / or intestinal pain and / or dysfunction of the intestinal microbiota and / or fatigue and / or weight loss, and / or suffering from a decrease in defenses immune systems and / or wishing to strengthen their immune defenses, in particular humans practicing high-intensity sporting activity and / or presenting intestinal dysfunction. - oral or sublingual administration of an effective quantity of a composition comprising an extract of Tetradesmus sp., advantageously T. obliquus 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, and / or modulate the intestinal microbiota.

[0109] In particular, the method is not intended for young children under 4 years old, preferably under 3 years old, preferably under 2 years old, and very preferably for newborns.

[0110] Another subject matter 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. REFERENCES:

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[0119] Lee, D.M.; E Ecton, K.; Trikha, S.R.J.; Wrigley, S.D.; Thomas, K.N.; Battson, M.L.; Wei, Y.; Johnson, S.A.; Weir, T.L.; Gentile, C.L. Microbial Metabolite Indole- 3-Propionic Acid Supplementation Does Not Protect Mice from the Cardiometabolic Consequences of a Western Diet. Am. J. Physiol. Gastroint. Liver Physiol. 2020.

[0120] Manter, D.K.; Korsa, M.; Tebbe, C.; Delgado, J.A. myPhyloDB: A local web server for the storage and analysis of metagenomic data. Database 2016, 2016, 39.

[0121] Watson, D., Clark, L. A., & Tellegen, A. (1988). Development and validation of brief measures of positive and negative affect: The PANAS scales. Journal of Personality and Social Psychology, 54(6), 1063–1070. EXEMPLES

[0122] Exemple 1 : Obtention d’une composition selon l’invention

[0123] Exemple 1a) Extrait de Tetradesmus sp. et composition le comprenant:

[0124] The strain of Tetradesmus sp used in the invention was first isolated in Germany in 1976. Two separate strains were used in the invention and were obtained from the collections of the University of Austin, Texas, USA (Culture Collection of Algae, strain UTEX 393) and the Culture Collection of Algae & Protozoa (CCAP 276 / 48).

[0125] 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:

[0126] 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 excipient nutraceutically acceptable has been incorporated into the composition. The resulting composition is in oily (liquid) form.

[0127] This composition was then tested in the pre-clinical studies described in Examples 2 and 3a).

[0128] Example 1b) Extract of Tetradesmus sp. and composition comprising it:

[0129] 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 co-solvent (10%), at a temperature of 50°C and a pressure of 150 bars (15MPa).

[0130] 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.

[0131] Example 1c) Extract of Pavlova sp. and composition comprising it:

[0132] The Pavlova sp. strain used in the invention was first isolated in 1966 in the Atlantic Ocean and was obtained from the Culture Collection of Algae & Protozoa (CCAP 940 / 2). The strain was cultivated autotrophically 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 referred to as an oily extract) was incorporated into a composition as below:

[0133] 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 resulting composition is in oily (liquid) form and was used in the pre-clinical trial detailed in Example 3a).

[0134] Example 1d) Composition comprising an extract of Tetradesmus sp. and Pavlova sp.: each of the 2 oily extracts obtained in examples 1a) and 1c) 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 weight ratio of T. obliquus and P. gyrans extract respectively of 50 / 50. A final quantity 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.

[0135] Example 1e) 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. obliquus and P. gyrans extract respectively of 75 / 25. A final quantity 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.

[0136] Example 2: Effect of the composition according to the invention comprising an extract of Tetradesmus sp. on intestinal hyperpermeability and colon motility.

[0137] Example 2a) Effect on weight / length ratio, weight, length and colon lesions: improvement of intestinal hyperpermeability in mice.

[0138] Protocol: A preclinical study in mice was conducted as follows: a population of 50 8-week-old male C57Bl / 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. 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 acclimation and experimental phases, the mice were fed a standard diet (SAFE) and plain water ad libitum.

[0139] 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 Inflammatory Syndrome. A 5th group did not receive SSD treatment. Three of the four SSD-treated groups received a daily dose of the composition comprising T. obliquus extract (Example 1a) of 308, 617 or 1542 mg / mouse / day (equivalent to 50, 100 or 250 mg / human / day) for 21 days. The 4th SSD-treated group received a daily dose of a placebo composition (no T. obliquus extract, but MCT oil + α-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 stool) to 2 (severe diarrhea).

[0140] The results of macroscopic parameters are presented in Table 5.

[0141] A 0.5 cm fragment of colon was taken from the area of ​​inflammation and fixed in 4% formaldehyde solution for histological analysis. Some of the residual tissue was frozen at -80°C. until analysis. Weekly monitoring of the mice's weight (Table 2) and their food and water intake was carried out (Table 3). The presence of blood in the stool and the consistency of the stool were analyzed daily during the 21-day period, which combined with the weekly analysis of weight loss, allowed the establishment of a daily disease index (DDI) from 0 to 4 according to the following classification.

[0142] [Table 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

[0143] Result :

[0144] Table 2: Assessment of mean weight loss during treatment as a percentage compared to the untreated control at time 0 (AVG %).

[0145] [Table 2] AVERAGE 0 7 14 15 16 17 18 19 20 21 (%) / days Group 1 100.0 103.3 108.3 109.2 108.3 108.7 110.4 110.0 109.6 109.6 Group 2 98.7 102.9 104.1 105.0 102.5 102.9 102.9 96.6 90.8 85.8 placebo Group 3 100.4 104.2 109.2 109.2 107.1 107.5 106.7 100.0 94.8 91.2 dose 50 Group 4 99.6 100.4 104.2 105.0 100.4 101.7 100.0 94.9 89.1 85.8 dose 100 Group 5 99.6 102.5 105.0 105.8 102.5 103.3 103.3 97.9 92.0 87.0 dose 250

[0146] Group 1 of mice: untreated control (SSD);

[0147] Group 2 of mice: Control treated with SSD with placebo composition;

[0148] Group 3 of mice: Supplementation with composition at dose 50 (dose of 50mg / day / human);

[0149] Group 4 of mice: Supplementation with composition at dose 100 (dose of 100mg / day / human);

[0150] Group 5 of mice: Supplementation with composition at dose 250 (dose of 250mg / day / human).

[0151] Conclusion: SSD treatment had very little effect on the weight of the mice during treatment, i.e. a 15% weight loss was measured after 21 days in the SSD-treated mice (Group 2 placebo). On the other hand, supplementation with the composition according to the invention (Composition according to Example 1a) in the SSD-treated mice did not induce any weight variation compared to 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.

[0152] Table 3: Dietary control during treatment

[0153] [Table 3] Group Quantity of food ingested Volume of water ingested (g / mouse / day) in % per (mL / mouse / day) in % compared to the untreated control compared to the untreated control (group 1) (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

[0154] 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 it is comparatively less decreased in mice having received the supplementation with composition according to the invention (Groups 3 to 5).

[0155] Table 4: DAI index (Daily disease activity index):

[0156] [Table 4] Day 0 1 2 3 4 5 6 7 Group 1 0 0 0.1 0 0 0.1 0.2 0 (untreated) 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**** 4.1**** 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**** 6.1****

[0157] (*p<0.05; ***p<0.001; ****p<0.00001 p values ​​test 2-way Anova and Bonferroni's post-hoc test)

[0158] Conclusion: SSD treatment significantly increased the index within 7 days (Group 2) compared to the untreated control group (Group 1). However, supplementation with the composition according to the invention (Composition according to Example 1a)) limited this increase, with 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.

[0159] Table 5: Macroscopic evaluations of the analyzed colon fragments

[0160] [Table 5] Group Mean Colon Weight Colon Length (cm) as % of Control (P)(mg) Untreated (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

[0161] Conclusion: SSD treatment reduced the average colon length by more than 40% (Group 2). The daily intake of the composition according to the invention comprising an extract of T. obliquus (Ex. 1a)) in the diet, on the other hand, made it possible to reduce this percentage to 31.4% (Group 3).

[0162] Example 2b) Effect on colon motility (isotonic contractions)

[0163] Protocol: A portion of the colon fragments dissected according to the protocol of Example 2a) were washed and then incubated in Krebs-Ringer solution for a period of 30 minutes at a temperature of 37°C, attached to an isotonic transducer (MLT7006 Isotonic Transducer, Hugo Basile, Comerio, Italy) and immersed in a bath maintained at 37°C and containing 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.

[0164] 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.

[0165] [Table 6] Group Amplitude (mN) in % by Frequency of contractions compared to group 1 (AVG) (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

[0166] (* p<0.05 post hoc ANOVA one-way statistical analysis (Bonferroni's post-hoc test))

[0167] Conclusion: SSD treatment, by altering the excitability of sensorimotor neurons, disrupted enteric cholinergic neurotransmission and suppressed smooth muscle responsiveness, inducing a decrease in contractions of the tested colon fragments. In SSD-treated mice that received daily supplementation with the composition according to the invention (Example 1a)), colon motility was restored by increasing the amplitude of contractions of the tested colon fragments, without impacting the frequency of these contractions, which remained similar to that measured in the non-SSD-treated control.

[0168] The composition according to the invention comprising an extract of T. obliquus is thus effective in improving colon motility, and therefore in improving intestinal transit.

[0169] Example 2c) Clinical evaluation in humans of the effect of the composition according to the invention on gastrointestinal health (intestinal barrier, intestinal transit):

[0170] Protocol: A human clinical trial was conducted on a population of 50 healthy individuals aged 18 to 55 years, with a body mass 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. obliquus extract according to example 1a) or a dose of 100 mg of a placebo composition without said composition (MCT Oil as control) in capsule form.

[0171] Exclusion criteria were: - BMI >30.0 or <18.0; - Smoking or using other tobacco products; - Diagnosed bowel diseases; - Pregnant or breastfeeding individuals; - Regular use of statins, metformin, steroids, NSAIDs or monoamine oxidase (MAO) inhibitors; - Clinically diagnosed mental disorders (clinical depression, bipolar disorder, etc.)

[0172] Participants were excluded from the clinical trial if they no longer met the inclusion criteria (or met the exclusion criteria during the trial). Weight, height, hip measurements, 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 the clinical trial started, and 2 weeks and 4 weeks after the start of the trial. Participants also completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire (Dimenäs et al. 1995; Kulich et al. 2008) at the start of the study and after 4 weeks of supplementation. This questionnaire assesses abdominal pain, reflux, indigestion, and constipation, rating symptoms on a scale of 1 to 7, and provides a global score known as the GSRS score. The results are presented in Table 9.

[0173] A measurement of the following fecal and blood biomarkers was carried out following a blood sample from each participant taken at the same times as above: - Analysis of the permeability and functionality of the intestinal barrier by stool sampling and dosage of short-chain fatty acids (SCFA) (Acetate, propionate, butyrate); briefly, stool samples were collected, stored at 4°C for 48 hours then a DNA sample was taken (cotton swab) from each stool sample and the sample was stored at -80°C for DNA extraction. The remaining stool samples were used for the analysis of short-chain fatty acids (volatile) by gas chromatography coupled with mass spectrometry known to those skilled in the art, after derivatization with isobutyl chloroformate and isobutanol of the undried samples.- Analysis of the intestinal microbiota by genomics and measurement of the Shannon index after sequencing of 16S RNAs as follows: Extraction of genomic DNA 16S RNA sequencing: Fecal DNA a. was extracted using the FastDNA® kit (MP Biomedicals). The V4 region of the 16S RNA was amplified according to the Earth Microbiome Project protocol (https: / / earthmicrobiome.org / ) using the 515F-806R primer set (Caporaso et al., 2012) containing a unique 12 bp Barcode sequence included in the reverse primer. Sequencing cycles and conditions were described in Lee et al., 2020. The amplified sequences were imported for analysis into QIIME 2 software (Bolyen et al., 2019). Shannon index measurement: The sequences were processed, concatenated, and GreenGenes software version 13.8 was used for taxonomic assignments. Sequences suspected of contamination were eliminated. MyPhyloDB software (version v.1.2.0) was used for data analysis (Manter DK et al., 2016): Microbial diversity of stool samples was measured via the Shannon index using QIIME 2 software and differences in abundance between microbial taxa were calculated via MyPhyloDB software by univariate analysis of covariance. The Shannon index measures the diversity of the microbial population within the stool samples collected. A high Shannon index typically characterizes a diverse and therefore healthy microbial population.

[0174] Results :

[0175] [Table 7] Measurement of fecal butyrate quantity: Time n Composition % Deviation- n Composition Deviation- % tetradesmus Decrease placebo (week) ion type type Decrease Ex.1a) T0 28 3.069 2.126 26 2.236 1.282 T4 27 2.113*† -31.15% 1.157 25 2.848 1.323 +3.19%

[0176] † p=0.024 T4 versus T0, and * p<0.05 T4 versus T4 placebo (Anova test).

[0177] Conclusion: The measurement of the amount of butyrate in the stools of the population showed a statistically significant effect of the composition comprising the extract of T. obliquus after 4 weeks of oral administration by reducing the amount of butyrate in the stools by more than 30%. The composition comprising the extract of T. obliquus is therefore effective in facilitating intestinal absorption of butyrate and thus improve intestinal transit and strengthen the intestinal barrier.

[0178] [Table 8] Increase in Shannon index: Time Composition % n Composition % n (week) tetradesmus Increase placebo Increase Ex.1a) T0 2.264 100 28 2.530 100 26 T2 2.357 104.10 28 2.560 101.18 25 T4 2.490† 109.98 27 2.498 98.73 24

[0179] † p = 0.052 T4 versus T0 (Anova test)

[0180] Conclusion: The Shannon index, reflecting the diversity of the microbial community in the stools analyzed, increased after 4 weeks of oral administration of the composition comprising the T. obliquus extract, unlike the placebo. The composition therefore has the capacity to modulate the intestinal microbiome.

[0181] [Table 9]: Questionnaire GSRS Score Composition N T0 Deviation- T4 Deviation- Average standard decrease between T4 and T0 Score GSRS Composition 28 2.12 0.78 1.64† 0.47† -22.6% tetradesmus Ex.1a) Composition 28 1.87 0.58 1.75 0.66† -6.41% placebo Composition Score 28 2.66 1.03 2.16† 1.25† -18.79% constipation tetradesmus Ex.1a) Composition 28 1.87 0.81 1.87 1.05 0% placebo Score Composition 28 2.44 0.96 1.78 0.69† -27.04% tetradesmus indigestion Ex.1a) Composition 28 2.27 0.75 2.08 0.97 -8.37% placebo

[0182] † p< 0.01 T4 versus T0 (Anova test)

[0183] Conclusion: The results of this questionnaire showed that the population surveyed considered that the symptoms of indigestion (bloating, intestinal discomfort related to digestion) as well as the symptoms of constipation (frequency of hard stools, bowel movements) decreased between the start of the clinical study (T0) and after 4 weeks of oral administration of the composition according to the invention. These results support the effectiveness of the composition comprising the T. obliquus extract on the improvement of gastrointestinal disorders, in particular uncomfortable disorders.

[0184] Example 3: Effect of the composition according to the invention on the maintenance and increase of immune defenses

[0185] Example 3a) Immunity maintenance effect in immunocompromised mice and enhancement of the immune response in response to pulmonary infection by P. aeruginosa:

[0186] 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 obliquus extract described in Example 1a) as part of their daily dietary intake (Group 2: dose of 50mg / kg body weight in human equivalent; Group 3: dose of 100mg / kg body weight in human equivalent and Group 4: dose of 250mg / kg in human equivalent). Group 1 control 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).

[0187] 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 first injection at a concentration of 150 mg / kg mouse weight at time D-4 and then a second injection (100 mg / kg mouse weight) at time D-1 (9 days after the start of the trial).

[0188] At time D0 (10 days after the start of the trial), blood samples were taken from 6 mice from the 6 groups to measure the amount of leukocytes, lymphocytes, monocytes and neutrophil granulocytes in the blood (plasma). The results are shown in Table 11 (n=6).

[0189] Immediately following the blood collection at D0, the groups of mice except one control group (Group 7) were infected by intranasal inoculation of Pseudomonas aeruginosa (1 x 10 5 CFU / mouse) (dilution in Phosphate Buffer Saline). Two days after inoculation (D+2), blood samples were taken from groups 1 to 6 of mice (Table 11). At the same time (D+2), lung fragments from 6 mice from groups 1 to 6 were collected for measurement of bacterial load (CFU) analysis by flow cytometry.

[0190] 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 PBS buffer. The samples obtained were deposited on agar plates 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 bacterial load measurement are presented in Table 14.

[0191] For analysis of lung fragments by flow cytometry, lung fragments were dilacerated, pulmonary blood cells were lysed with lysis buffer, stained with Live Dead Blue-UV and then fixed with paraformaldehyde (3.6%) in the presence of a mixture of specific antibodies including all the cell markers below (and their commercial references: Table 10). Cells were counted by flow cytometry. The results are presented in Table 13.

[0192] [Table 10] CD45-Viogreen (130-110-665) SiglecF-PE (130-112-332) CD11b-APC (130-113-802) CD64-PeVio (770130-119-659) CD11c-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)

[0193] Blood inflammatory interleukin IIβ was also measured (Table 12). The weight of the mice (12 mice in each group) was monitored daily throughout the trial (Table 15).

[0194] Results :

[0195] Table 11: Average number of immune cells (x10 6 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)).

[0196] [Table 11] Leukocyte Lymphocyte Monocyte Granulocyte Group 1: D-10 control (placebo composition) 100.0 100.0 100.0 100.0 Group 1: D0 control (placebo composition) 16.5 14.3 16.7 20.9 Group 2: compo tetradesmus Ex.1a) D0 (dose 50) 46.5 36.4**** 38.9** 69.8 Group 3: compo tetradesmus Ex.1a) D0 (dose 100) 38.5 32.5*** 33.3* 53.5 Group 4: compo tetradesmus Ex.1a) D0 (dose 250) 49.1** 44.2**** 50.0**** 55.8 Group 5: Pavlova composition Ex.1c) D0 (dose 50) 60.82** 43.29**** 52.13*** 95.35*** Group 6: Pavlova composition Ex.1c) 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: tetradesmus composition Ex.1a) D+2 (dose 50) 40.74*** 31.14*** 31.01** 63.08*** Group 3: tetradesmus composition Ex.1a) D+2 (dose 100) 32.47** 27.41* 25.34 44.75* Group 5: Pavlova composition Ex.1c) D+2 (dose 50) 13.75 11.02 9.67 20.39 Group 6: Pavlova composition Ex. 1c) D+2 (dose 250) 23.86 18.75 17.99 35.69

[0197] (* p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001 versus group 1 D0 or group 1 D+2).

[0198] Conclusion :

[0199] 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).

[0200] 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 this by at least half in the case of monocytes and granulocytes at the dose of 250mg / kg. Lymphocytes being cells characteristic of the response acquired (adaptive) immune response, and monocytes and granulocytes being characteristic of the innate immune response, the composition comprising the extract of T. obliquus is effective in maintaining and increasing immune defenses, being effective on both the adaptive response and the innate response.

[0201] The composition according to example 1c) (Extract of Pavlova gyrans) also made it possible to limit even more effectively the drastic decrease in all 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 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.Since monocytes are cells characteristic of the innate response, the composition according to example 1c) 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 1c) is also effective on the adaptive immune response.

[0202] 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.

[0203] Response to P. aeruginosa infection: Infection did not significantly decrease the amounts of cell types analyzed 2 days later infection in the immunocompromised control group (group 1), compared to the quantities measured at time 0 (D0). On the other hand, if the daily intake of the composition according to example 1c) (P. gyrans extract) did not strictly speaking make it possible to limit this decrease over time following the infection, the composition according to example 1a) (T. obliquus extract) significantly maintained or almost maintained the quantities of the cell types analyzed at least two days after infection.

[0204] 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 obliquus, 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 13, efferocytic macrophages) but also on the reduction of the bacterial load in the lungs two days after infection (Table 14).

[0205] Table 12: Measurement of the amount of interleukins ILβ in the blood two days after pulmonary infection by P. aeruginosa.

[0206] [Table 12] Group Amount of IL-1β 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 comp. Ex.1a) D+2 (dose 50) 40.89 Group 3: tetradesmus comp. Ex.1a) D+2 (dose 100) 8.72 Group 4: tetradesmus comp. Ex.1a) D+2 (dose 250) 9.37*

[0207] (* p<0.05 versus Group 1)

[0208] Conclusion: The composition comprising the extract of Tetradesmus obliquus (Ex. 1a) significantly decreased at a dose of 250 mg / kg the amount of inflammatory interleukin Ilβ 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 decreasing the amounts of one of the characteristic proinflammatory markers, interleukins Ilβ.

[0209] Table 13: Mean number of immune cells (in % of live cells) measured in the lungs by flow cytometry two days after lung infection (mean % reported to the quantity of the cell type in the uninfected control group).

[0210] [Table 13] Macrophages Group NKT CD4+ CD8+ Efferocytic Group 7 uninfected D+2 130.48 206.34 182.61 46.63 Group 1: placebo composition 100.00 100.00 100.00 100.00*** MCT D+2 Group 2: tetradesmus composition 199.83* 170.26 123.91* 112.73 Ex.1a) D+2 (dose 50) Group 3: tetradesmus composition 150.02 201.75* 132.01* 162.76 Ex.1a) D+2 (dose 100) Group 4: tetradesmus composition 131.45 246.81 129.78 144.51 Ex.1a) D+2 (dose 250) Group 6: Pavlova composition 124.54 123.41 84.66 206.63** Ex. 1c) D+2 (dose 250)

[0211] († T-test; (* p<0.05 versus Group 1; ** p<0.01 versus Group 1; *** p<0.01 versus Group 7))

[0212] P. aeruginosa infection induced a decrease in the amount of NKT lymphocytes and CD4 and CD8 T lymphocytes in the placebo group 1 (Composition including MCT oil). In contrast, infection pulmonary infection tended to increase the amount of efferocytic macrophages in group 1 compared to the uninfected control group.

[0213] The composition according to Example 1a) comprising a T. obliquus extract limited the decrease in CD8 T lymphocytes at the administered doses, and tended to limit the decrease or tended to almost maintain the amount 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.

[0214] The composition according to example 1c) comprising an extract of P. gyranstended 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 (D0) by this same composition (Table 11) 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.

[0215] Table 14: Measurement of bacterial load in the lungs at time D+2 after infection by P. aeruginosa.

[0216] [Table 14] Group MOY Standard deviation (Log10 of CFU (mL)) Group 1: control D+2 (MCT placebo composition) 6.3 0.4 Group 2: tetra composition Ex.1a) D+2 (dose 50) 6.4 0.3 Group 3: tetra composition Ex.1a) D+2 (dose 100) 5.2 0.2 Group 4: tetra composition Ex.1a) D+2 (dose 250) 4.3 0.2 Group 5: Pavlo composition Ex.1c) D+2 (dose 50) 4.3 0.2 Group 6: Pavlo composition Ex. 1c) D+2 (dose 250) 2.3*** 0.5

[0217] (*** p<0.001 versus Group 1)

[0218] 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 compared to the bacterial load measured in the lungs of mice in the infected control group who received the placebo composition.

[0219] Table 15: Mouse weight measurement (mean % of weight at time D x compared to initial weight at time D-10) (n=6).

[0220] [Table 15] Group D-9 D-8 D-7 D-6 D-5 D-4 D-3 D-2 D-1 D0 D+1 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.1a) 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.1a) 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 Ex.1c) 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 Ex. 2.0 2.0 6.0 7.0 4.4 5.8 4.4 3.2 1.7 1.8 -0.5 -0.8 1c) dose 250 D+2

[0221] Conclusion: The weight of the mice in the control group not infected with P. aeruginosa increased during the trial. In contrast, the mice in the infected control group receiving a placebo composition (MCT oil) saw their weight decrease by up 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. obliquus (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 pre-clinical 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.

[0222] Example 4: Effect of the composition according to the invention on stress

[0223] As part of the clinical trial described in Example 2c), saliva samples were collected from each participant. α-amylase (sAA), chromogranin A (CgA), and lysozyme were assayed from these saliva samples. Similarly, blood samples were collected to measure blood-derived neurotrophic factor (BDNF), adrenocorticotropic hormone (ACTH), and cortisol. Blood and saliva samples were collected at time 0 (Initial Recruitment Visit), 2 weeks before the start of the trial, on the day the clinical trial began, and 2 weeks and 4 weeks after the start of the trial.

[0224] Results :

[0225] Decrease in salivary chromogranin A (CgA) after 4 weeks (T4):

[0226] [Table 16] CgA n T0 Standard deviation T4 Standard deviation Composition tetradesmus Ex.1a) 25 1053.63 1116.7 677.97*† 598.40 Placebo composition 28 1305.92 1063.49 1260.51 1054.31

[0227] † p<0.05 T4 versus T0; * p<0.05 T4 Tetradesmus composition versus T4 placebo (Anova test).

[0228] Conclusion: The amount of salivary chromogranin decreased by more than 30% after 4 weeks of daily oral supplementation of the composition comprising the Tetradesmus obliquus extract according to the invention, while the amount of chromogranin decreased by 3% over the same time. The T. obliquus extract is therefore effective in reducing one of the characteristic markers of stress in humans.

[0229] Example 5: Effect of composition on mood

[0230] In the clinical study described in Example 2c), the population of interest responded to a questionnaire called the PANAS (Positive and Negative Affect Schedule) questionnaire (or scale) (Watson et al., 1988) at the start of the study (T0) and after 4 weeks of oral administration of the composition according to Example 1a). This questionnaire allows the measurement of an individual's negative and positive affects and therefore characterizes their mood.

[0231] Results :

[0232] [Table 17] Negative affects N T0 Standard deviation T4 Standard deviation Decrease between T4 and T0 Composition 28 28.43 4.03 25.85† 3.83 -9%* tetradesmus Ex.1a) Placebo composition 27 26.77 3.79 26.23 4.19 -2%

[0233] † p < 0.0001 T4 vs T0 and * p < 0.05 T4 Tetradesmus composition vs T4 placebo (Anova Test)

[0234] Conclusion: Oral administration of the composition comprising T. obliquus extract for 4 weeks induced a decrease in negative affects of the population who responded to the questionnaire. The composition therefore seems to play a role in mood.

Claims

Claims

1. Oral or sublingual composition comprising an extract of Tetradesmus sp. and / or an extract of Pavlova sp., and at least one nutraceutically 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 a medium-chain triglyceride oil, 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 it is still 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 from 29%; - a coconut oil content ranging from 20% to 90%, advantageously 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%.

7. Composition according to any one of claims 1 to 5, characterized in that it comprises by 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%; - A content of α-tocopherol 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 extract of Tetradesmus sp. and / or the extract of Pavlova sp.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, orodispersible 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, advantageously in the form of a cold dispersible 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 of 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 use in: - 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 - modulating the intestinal microbiota 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 for use according to claim 17 for improving intestinal transit, advantageously in humans, by modulating the quantity of butyrate produced, and / or by improving intestinal absorption of butyrate.

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

20. 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 and / or having intestinal dysfunction and / or suffering from intestinal discomfort.

21. 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.

22. Composition for its use according to claim 21 to provide a complete immune response.

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