Feed additive for improving performance of farming animals

Abstract

The present application describes a composition for feeding to animals, e.g., farming animals, that improves their performance. The composition comprises Satureja hortensis aerial parts, or an extract thereof, Glycyrrhiza glabra aerial parts, or an extract thereof, preferably Glycyrrhiza glabra leaves, or an extract thereof, Artemisia vulgaris aerial parts, or an extract thereof, Rubus fruticosus leaves, or an extract thereof, and a source of butyrate.

Description

[0001] Title: Feed additive for improving performance of farming animals

[0002] FIELD OF THE INVENTION

[0003] The present invention is in the field of feed additives for animals, e.g., farming animals, in particular feed additives to be added to animal feed to obtain an improved performance, e.g., increasing feed efficiency (i.e. , decreasing feed conversion ratio).

[0004] BACKGROUND OF THE INVENTION

[0005] Antimicrobial agents have been used as antibiotic growth promoters in livestock feed for many decades. However, resistance to such antimicrobial agents is now considered a serious threat to human health. The use of antimicrobial agents as a growth promoter in livestock feed has been fully banned in the European Union since January 2006. At the same time, the demand for protein from animal origin is increasing, fuelled by the human population increase. Additionally, the food production needs to be more sustainable, requiring that more is produced with less. Taken together, food animal production needs to be more and more effective.

[0006] These developments have initiated a surge of exploring feed additives that improve performance of farming animals yet do not induce resistance to bacteria. Phytogenic feed additives, also known as botanicals, are substances of plant origin added to animal diets with the aim of improving animal performance. Essential oils, herbs and spices all serve as sources for bioactive ingredients, e.g. phenols, polyphenols, flavonoids, terpenoids and others.

[0007] Enterococcus is a large genus of lactic acid bacteria of the phylum Firmicutes. Enterococci are tolerant of a wide range of environmental conditions: extreme temperature (10- 45°C), pH (4.5-10.0), and high sodium chloride concentrations. Among the Enterococcus species, some are known to be opportunistic pathogens when they get outside the gut. This is the case with respect to E. avium, E. gallinarum and E. cecorum, wherein E. cecorum is important in terms of economic losses sustained by poultry farmers in broiler chicken production chain.

[0008] Enterococcus cecorum is a normal inhabitant of the intestine of birds and other vertebrates such as horses, cattle, pigs, dogs, cats, canaries, pigeons, turkeys and Muscovy ducks. It is considered an emerging pathogen of poultry and other avian species. Femoral head necrosis and spondylitis have been described as the main pathological changes in infected chickens. A part of the normal gut flora, disruptions or insult to normal gut function can result in Enterococcus cecorum translocation to the spine of birds. Enterococcus cecorum infections in the spine lead to vertebral and arthritic lesions, lameness and mortality in a condition known as enterococcal spondylothesis or "kinky back". Spondylitis, referred to as "kinky back" by poultry producers, has been known in commercial production for many years and is typically seen in heavy, fast-growing birds, especially males and broiler breeders.

[0009] Highly pathogenic and antibiotic-resistant strains of Enterococcus cecorum continue to cause economic losses to the broiler chicken industry. Thus, routine farm hygiene procedures and antimicrobial therapy have proven insufficient to control outbreaks of pathogenic Enterococcus spp., especially, Enteroccocus cecorum.

[0010] It is an object of the present invention to provide a composition or an animal feed to improve performance of farming animals, e.g., increasing feed efficiency. Alternatively or additionally, it is an object of the present invention to provide a composition or animal feed that improves gut health and / or prevents gut damage, and that may prevent microbial translocation across the gut, and may alleviate or prevent enterococcosis.

[0011] SUMMARY OF THE INVENTION

[0012] The present disclosure provides a composition comprising Satureja hortensis aerial parts, or an extract thereof, Glycyrrhiza glabra aerial parts, or an extract thereof, preferably Glycyrrhiza glabra leaves, or an extract thereof, Artemisia vulgaris aerial parts, or an extract thereof, Rubus fruticosus leaves, or an extract thereof, and a source of butyrate.

[0013] The Satureja hortensis aerial parts, the Artemisia vulgaris aerial parts, the Glycyrrhiza glabra aerial parts, e.g., Glycyrrhiza glabra leaves, and / or the Rubus fruticosus leaves may be dried, and optionally ground.

[0014] The extract may be selected from the group consisting of an aqueous extract, ethanolic extract, methanolic extract, isopropanolic extract, ethylacetate extract, acetonic extract, hexane extract, a supercritical CO2 extract, or a combination of any of these.

[0015] The present disclosure also provides an animal feed comprising a composition as taught herein.

[0016] The animal feed may comprise said composition in an amount of about 5 to about 10000 mg / kg feed.

[0017] The present disclosure further relates to use of a composition as taught herein or an animal feed as taught herein for improving performance of animals, e.g., increasing body weight gain, increasing average daily gain, and / or increasing feed efficiency.

[0018] The present disclosure also provides a composition as taught herein or an animal feed as taught herein for use as a medicament, e.g., for use in preventing and / or reducing infection, e.g., microbial infection, and / or diseases caused by such infection, e.g., microbial infection, in an animal.

[0019] The microbe may be selected from the group consisting of a fungus, a yeast, a virus, a parasite, a Gram-positive bacterium, and a Gram-negative bacterium. The microbe may be a Gram-positive bacterium, preferable of the genus Enterococcus, such as from the species E. avium, E. gallinarum and E. cecorum.

[0020] In an embodiment, the disease is selected from the group consisting of enterococcosis, coccidiosis, sepsis, and spondylitis.

[0021] The disclosure also relates to a method of inhibiting translocation of pathogenic microbes such as Enteroccocus spp., e.g., E. cecorum, in an animal, said method comprising administering to said animal a composition as taught herein or an animal feed as taught herein.

[0022] The disclosure is further concerned with a method of improving gut health and / or preventing gut damage, said method comprising the step of administering to said animal a composition as taught herein or an animal feed as taught herein.

[0023] In an embodiment, the number of butyrate- producing microbes and / or lactate-producing microbes are increased in the gut.

[0024] The composition or feed additive may be intended for inclusion in feed for farming animals or companion animals.

[0025] The animal may be selected from farming animals and companion animals. The farming animals may be selected from the group consisting of poultry, swine, ruminants, e.g., beef cattle and dairy cattle, fish, e.g. salmon, trout, seabream, sea brass, tilapia, tuna, and the like, and crustaceans, e.g., shrimp. The companion animals may be selected from the group consisting of ornamental fish, cats, dogs, horses, rabbits, guinea pigs, and hamsters.

[0026] GENERAL DEFINITIONS

[0027] In the following description and examples, a number of terms are used. In order to provide a clear and consistent understanding of the specification and claims, including the scope to be given to such terms, the following definitions are provided. Unless otherwise defined herein, all technical and scientific terms used have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The disclosures of all publications, patent applications, patents and other references cited herein are incorporated herein in their entirety by reference.

[0028] The term “aerial part” when referring to a plant refers to anything that exists in the air or in the space above a solid surface. The aerial part of plants simply denotes the structures of a plant that are above ground, including the stems, leaves, petioles, flowers, fruits and seeds. The term includes any aerial part alone, e.g., leaves, or stem, or the entire aerial part (i.e., all plant parts above the ground).

[0029] The term “leaves” when referring to a plant refers to any usually flattened green outgrowth from the stem of a vascular plant. As the primary sites of photosynthesis, leaves manufacture food for plants, which in turn ultimately nourish and sustain all land animals. Botanically, leaves are an integral part of the stem system. They are attached by a continuous vascular system to the rest of the plant so that free exchange of nutrients, water, and end products of photosynthesis (oxygen and carbohydrates in particular) can be carried to its various parts.

[0030] The term ‘farming animal’ refers to animals that are kept or raised for agricultural purposes, like for consumption or to generate income by for example meat, eggs or milk products. Farming animals can be grouped based on their digestive system. Such groups include monogastric, ruminant and pseudo-ruminant animals.

[0031] The term “pellets” or “feed pellets” as used herein refers to small particles or a body typically created by compressing an original material, for instance a mixture of raw feed material, typically fermentable feed ingredients such as grains, cereals, legumes, roughage, and the likes. Feed pellets may also comprise other feed ingredients such as meat meal, fish meal, bone meal, by-process products, oil, fat, fillers or any mixture thereof, etc., as well as minerals, vitamins and trace elements and others. Animal feed pellets vary in their composition as well as structural properties (e.g. hardness, density, durability, shape, size, etc.) depending on the nutritional needs, eating habits, digestive system (monogastric system, ruminant digestive system, etc.) and habitat (e.g., aquatic, terrestrial, domestic, etc.) of the animal for which the feed pellet is intended. Animal feed pellet may have any size, shape (e.g. round, rectangular, cylindrical, etc), weight and / or length. It is understood that the weight of the feed pellet will depend on the feed pellet composition per se (e.g. some ingredients have a greater weight or density than others) as well as the shape, size and length of the finished feed pellet product. It is known that the size, shape, weight and / or length of the feed pellet will influence pellet durability. This is true for any method for making feed pellets, including method as taught herein. It is further commonly agreed in the field of agriculture and animal nutrition that animals (e.g. young and adult livestock animals like beef (e.g. beef calf), dairy cows (e.g. dairy calf), and pigs, etc.) benefit more or make better gains (e.g. weight gain, increased height, enhanced growth curve) on pelleted feed than a meal ration because pelleted feed is in a more concentrated, readily edible and palatable form than meal or mash ration. Pelleted feed has been shown to ease food intake and minimize feed waste during the eating process. It was shown that most animals, if given the choice between the same feed in a pellet or a mash form, will prefer the pellet form. Animal feed pellets are typically produced on an industrial scale using for example a pelleting process. The skilled person is well-acquainted with processes for producing animal feed pellets.

[0032] The term “secondary plant constituents” as used herein refers to specialized compounds present in plants that do not aid in the growth and development of plants but are required for the plant to survive in its environment. Such secondary plant constituents may be essential for communicating with other organisms in mutualistic (e.g. attraction of beneficial organisms such as pollinators) or antagonistic interactions (e.g. deterrent against herbivores and pathogens). They may further assist in coping with abiotic stress such as increased UV- radiation. The broad functional spectrum of specialized metabolism is still not fully understood.

[0033] The term “translocation” as used in the context of microbes is defined as the passage of viable microbes such as bacteria from the gastrointestinal (Gl) tract to extraintestinal sites, such as the mesenteric lymph node complex (MLN), liver, spleen, kidney, and bloodstream.

[0034] The term ‘about’, as used herein indicates a range of normal tolerance in the art, for example within 2 standard deviations of the mean. The term “about” can be understood as encompassing values that deviate at most 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1 %, 0.5%, 0.1 %, 0.05%, or 0.01% of the indicated value.

[0035] The terms “comprising” or “to comprise” and their conjugations, as used herein, refer to a situation wherein said terms are used in their non-limiting sense to mean that items following the word are included, but items not specifically mentioned are not excluded. It also encompasses the more limiting verb “to consist essentially of” and “to consist of”.

[0036] Reference to an element by the indefinite article "a" or "an" does not exclude the possibility that more than one of the elements is present, unless the context clearly requires that there be one and only one of the elements. The indefinite article "a" or "an" thus usually means "at least one".

[0037] DETAILED DESCRIPTION OF THE INVENTION

[0038] This patent application has been drafted into sections. However, these sections should not be read in isolation. Unless otherwise specified, each section is to be read in combination with the other sections. The various optional and preferred features can also be combined, even when taken from different parts of the specification. Likewise, all “aspects” and “embodiments” can be combined. No separation of embodiments is intended, unless explicitly stated.

[0039] The present inventors have surprisingly found that a composition comprising Satureja hortensis aerial parts, Glycyrrhiza glabra leaves, Artemisia vulgaris aerial parts, Rufus fruticosus leaves, and a source of butyrate, e.g. butyrate salts, increased body weight gain and average daily gain, and decreased Feed Conversion Ratio (FCR) and bodyweight adjusted FCR in broiers.

[0040] Compositions, feed additive, animal feed

[0041] In a first aspect, the present disclosure provides a composition comprising Satureja hortensis aerial parts, or an extract thereof, Glycyrrhiza glabra aerial parts, or an extract thereof, preferably Glycyrrhiza glabra leaves, or an extract thereof, Artemisia vulgaris aerial parts, or an extract thereof, Rubus fruticosus leaves, or an extract thereof, and a source of butyrate.

[0042] The aerial parts or leaves used in the composition taught herein, may be used fresh or may be dried by any means known in the art. The skilled person knows suitable drying technologies. For example, drying may take place using a drum drier, belt dryer, dehydrator drying, vacuum drying, microwave drying, or infrared-drying, or natural drying (sun drying). Thus, the composition taught herein may comprise dried Satureja hortensis aerial parts, dried Artemisia vulgaris aerial parts, dried Glycyrrhiza glabra aerial parts, preferably dried Glycyrrhiza glabra leaves, and / or dried Rufus fruticosus leaves. The plant parts may be dried to the extent that spoilage thereof is prevented.

[0043] Prior to or after drying, preferably after drying, the aerial parts or leaves may be ground to any suitable size. For example, the fresh or dried aerial parts or leaves, may be ground to an average particle size of smaller than 2 mm, preferably smaller than 1.5 mm, even more preferably smaller than 1 mm, yet more preferably smaller than 0.8 mm, even more preferably smaller 0.6 mm, most preferably smaller than 0.5 mm.

[0044] The composition may comprise aerial parts or leaves of all plants or may comprise aerial parts or leaves of some plants, whilst it further comprises an extract of one or more other plants contained therein. Alternatively, the composition may comprise an extract of all plants.

[0045] The composition taught herein may advantageously comprise Satureja hortensis aerial parts, Glycyrrhiza glabra aerial parts, preferably Glycyrrhiza glabra leaves, Artemis vulgaris aerial parts, and Rubus fruticosus leaves. The plant parts used may be dried and ground to a suitable size for inclusion in animal feed.

[0046] The composition may comprise the various plants or plant parts, or plant extracts in any ratio. For example, the composition may comprise 5-95 wt%, such as 10-90 wt%, or 15-85 wt%, 20-80wt%, 25-75 wt%, 30-70 wt%, 35-65 wt%, 40-60 wt%, or 45-55 wt%, Rubus fruticosus aerial parts, or Rubus fruticosus leaves, preferably dried and ground, 2-95 wt%, such as 10-90 wt%, or 15-85 wt%, 20-80wt%, 25-75 wt%, 30-70 wt%, 35-65 wt%, 40-60 wt%, or 45-55 wt%, Glycyrrhiza glabra aerial parts, or Glycyrrhiza glabra leaves, preferably dried and ground, 5-95 wt%, such as 10-90 wt%, or 15-85 wt%, 20-80wt%, 25-75 wt%, 30-70 wt%, 35-65 wt%, 40-60 wt%, or 45-55 wt%, Artemisia vulgaris aerial parts, preferably dried and ground, and 1-95 wt%, such as 2-90 wt%, or 5-85 wt%, 10-80wt%, 15-75 wt%, 20-70 wt%, 30-65 wt%, 40-60 wt%, or 45-55 wt%, Satureja hortensis aerial parts, preferably dried and ground.

[0047] The butyrate source may be any butyrate source such as an inorganic butyrate salt, e.g., sodium butyrate, calcium butyrate, potassium butyrate, magnesium butyrate, etcetera, or any mixture thereof, a mono-, di-, or tributyrin, or any other butyrate ester, or any mixture thereof. The butyrate salt may be embedded in a matrix, e.g., a fat matrix, e.g., comprising saturated fats such as lard, tallow, or fully or partially hydrogenated vegetable oils, to suppress its smell. The skilled person is capable of selecting a suitable butyrate source for use in the present context. The composition may comprise about 10-50 wt%, such as about 15-45 wt%, about 20-40 wt%, or about 25-35 wt% of the butyrate source, preferably of butyrate salt, more preferably of sodium butyrate, calcium butyrate, potassium butyrate, magnesium butyrate, or the like.

[0048] The present disclosure further provides a feed additive comprising the composition taught herein. Moreover, the present disclosure provides use of the composition taught herein as a feed additive.

[0049] Said feed additive may further comprise vitamins, minerals, organic acids, antioxidants, and / or pigments. Said feed additive may be provided in the form a premix. The feed additive is preferably intended for inclusion in feed for farming animals or companion animals.

[0050] The composition taught herein or the feed additive may be supplied with written instructions to include it into animal feed in an amount of the composition taught herein of about 1 mg / kg to about 10000 mg / kg of feed, preferably about 5 mg / kg to about 8000 mg / kg of feed, more preferably about 10 mg / kg to about 6000 mg / kg of feed, even more preferably about 15 mg / kg to about 4000 mg / kg of feed, yet more preferably about 20 mg / kg to about 3000 mg / kg of feed, again more preferably about 25 mg / kg to about 2000 mg / kg of feed, such as about 30 mg / kg to about 1500 mg / kg of feed, about 40 mg / kg to about 1200 mg / kg of feed, about 50 mg / kg to about 1000 mg / kg of feed, or about 60 mg / kg to about 800 mg / kg of feed, or, in case an extract of one or more of the plants is used, an equivalent amount of extract.

[0051] The present disclosure also provides an animal feed comprising a composition as taught herein or a feed additive as taught herein.

[0052] The animal feed may be in any form suitable for ingestion by the relevant animal. For example, poultry feed may be in the form of crumble, mash, or pellets. Swine feed may be in the form of meal or pellets. Feed for fish and crustaceans is usually in the form of extruded or pressed pellets but may also be in the form of flakes. In an embodiment, the animal feed is in the form of a crumble, mash, meal, flakes, or pellets, which pellets may be extruded or may be pressed.

[0053] The animal feed generally comprises protein, fat, carbohydrates, minerals and vitamins. It may further comprise organic acids, and other feed additives. The skilled person knows how to formulate a suitable animal feed depending on the target animal.

[0054] The composition taught herein may be included in animal feed in an amount of about 1 mg / kg to about 10000 mg / kg of feed, preferably about 5 mg / kg to about 8000 mg / kg of feed, more preferably about 10 mg / kg to about 6000 mg / kg of feed, even more preferably about 15 mg / kg to about 4000 mg / kg of feed, yet more preferably about 20 mg / kg to about 3000 mg / kg of feed, again more preferably about 25 mg / kg to about 2000 mg / kg of feed, such as about 30 mg / kg to about 1500 mg / kg of feed, about 40 mg / kg to about 1200 mg / kg of feed, about 50 mg / kg to about 1000 mg / kg of feed, or about 60 mg / kg to about 800 mg / kg of feed.

[0055] Alternatively, or additionally, an equivalent amount of extract of the aerial parts or leaves of the respective plants may be used. Plant extraction is a process that aims to extract certain components (so-called secondary plant constituents, including alkaloids, terpenoids, saponins, phenolic compounds, flavonoids, and / or tannins) present in plants. It is a solid / liquid separation operation: a solid object (in the present case aerial parts or leaves of one or more of the plants of the composition taught herein, optionally dried and / or ground) is placed in contact with a fluid (the solvent). The plant components of interest are then solubilised and contained within the solvent. The solution thus obtained is the desired extract. The solvent may eventually be eliminated, although this is not required. The solvent may be any solvent suitable for preparing plant extracts for use in animal feed. Suitable solvents include, without limitation, polar solvents (e.g., water, alcohols such as ethanol, methanol and isopropanol), intermediate polar solvent (e.g., acetone, dichloromethane), and nonpolar solvents (e.g., ethylacetate, hexane, ether, chloroform). The skilled person may select a single solvent or two or more solvents to prepare an extract in accordance with the present disclosure. In general, extraction procedures include maceration, digestion, decoction, infusion, percolation, Soxhlet extraction, superficial extraction, ultrasound-assisted, and microwave-assisted extractions, supercritical fluid extraction (e.g. with supercritical carbon dioxide), accelerated solvent extraction, and solidphase extraction. Fractionation and purification of phytochemical substances may be achieved through application of various techniques such as liquid-liquid partitioning, cross-flow filtration techniques and chromatographic methods, such as paper chromatography, thin-layer chromatography, gas chromatography, and high-performance liquid chromatography, centrifugal partitioning chromatography. Finally, compounds obtained are characterized using diverse identification techniques such as mass spectroscopy, infrared spectroscopy, ultraviolet spectroscopy, and nuclear magnetic resonance spectroscopy, or any combination thereof. The skilled person is capable of selecting a suitable extraction method.

[0056] The amount of extract or extracts to be incorporated into the animal feed and / or feed additive may be determined by equating the content of one or more secondary plant constituents in the extract to those in the respective plant parts. An amount of extract that provides a content of one or more secondary plant constituents that is equivalent to the content of said one or more secondary plant constituents in the indicated amount of aerial parts or leaves may thus be incorporated into said animal feed.

[0057] In an embodiment, the extract is selected from the group consisting of an aqueous extract, ethanolic extract, methanolic extract, isopropanolic extract, ethylacetate extract, acetonic extract, hexane extract, or a supercritical CO2 extract, or a mixture of any of these. Alternatively, a mixture of solvents may be used for extraction, as set forth above. Methods and uses of the compositions, feed additive and animal feed

[0058] In an aspect, the present disclosure provides a method of feeding an animal, e.g., a farming animal or a companion animal, said method comprising the step of administering a composition, a feed additive, or an animal feed as taught herein to said animal.

[0059] In a further aspect, the present disclosure relates to use of a composition, a feed additive or animal feed as taught herein for increasing or improving performance of an animal, preferably a farming animal.

[0060] In another aspect, the present disclosure is concerned with use of a composition, a feed additive or animal as taught herein for increasing body weight gain, increasing average daily gain, increasing feed efficiency (i.e., decreasing feed conversion ratio), and / or decreasing bodyweight-adjusted feed conversion ratio.

[0061] In yet another aspect, the present disclosure provides a composition as taught herein or an animal feed as taught herein for use as a medicament, e.g., for use in in preventing, reducing the frequency and / or severity of, and / or treating a microbial infection in an animal, and / or diseases caused by such infection, e.g., in an animal. In an embodiment, the animal is infected with a microbe (“an infected animal”) or is at risk of being infected with a microbe. For example, the animal may be in an environment that puts disease pressure on the animal. As such, the animal may be facing a disease challenge such as a microbial challenge. In an embodiment, the animal may

[0062] In an embodiment, the microbe is selected from the group consisting of a fungus, a yeast, a virus, a parasite, a Gram-positive bacterium, and a Gram-negative bacterium.

[0063] In an embodiment, the microbe is a Gram-positive bacterium, preferable of the genus Enterococcus, such as from the species E. avium, E. gallinarum and E. cecorum.

[0064] The disease caused by the microbial infection may be selected from the group consisting of enterococcosis, coccidiosis, sepsis, and spondylitis.

[0065] In an aspect, the present disclosure further relates to a method of inhibiting translocation of pathogenic microbes such as Enteroccocus spp.in an animal, said method comprising administering to said animal a composition as taught herein or an animal feed as taught herein.

[0066] The disclosure is also concerned with a method of improving gut health and / or preventing gut damage, said method comprising the step of administering to said animal a composition as taught herein or an animal feed as taught herein. In an embodiment, the number of butyrate-producing microbes and / or lactate-producing microbes are increased in the gut.

[0067] Moreover, the present disclosure provides a method of increasing the number of butyrate-producing microbes and / or lactate-producing microbes in the gut or the microbiome of an animal, said method comprising the step of administering to said animal a composition as taught herein or an animal feed as taught herein. The present disclosure further provides a method of improving performance of animals, e.g., increasing body weight gain, increasing average daily gain, increasing feed efficiency (i.e., decreasing feed conversion ratio), and / or decreasing bodyweight-adjusted feed conversion ratio, said method comprising the step of administering a composition, a feed additive, or an animal feed as taught herein to said animals.

[0068] The animal may be a monogastric animal, a pre-ruminant animal, or a ruminant animal. The animals may be selected from farming animals and companion animals. The farming animals may de selected from the group consisting of poultry, swine, ruminants, e.g., beef cattle and dairy cattle, fish, e.g. salmon, trout, seabream, sea brass, tilapia, tuna, and the like, and crustaceans, e.g., shrimp. The companion animals may be selected from the group consisting of ornamental fish, cats, dogs, horses, rabbits, guinea pigs, and hamsters. In an embodiment, the animal is a broiler, broiler breeder, or laying hen.

[0069] In an embodiment, the benefits in performance obtained in animals fed the feed additive as taught herein or the composition taught herein or the animal feed taught herein are relative to results obtained animals (of the same species) fed an identical animal feed yet without such feed additive or composition or animal feed.

[0070] The present invention is further illustrated, but not limited, by the following examples. From the above discussion and the examples, one skilled in the art can ascertain the essential characteristics of the present invention, and without departing from the teaching and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Thus, various modifications of the invention in addition to those shown and described herein will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

[0071] EXAMPLES

[0072] Example 1

[0073] In this example, the effect of 250 ppm dietary inclusion of dried Rubus fruticosus leaves, 16 ppm dried Satureja hortensis aerial parts, 132 ppm dried Artemisia vulgaris aerial parts, 52 ppm dried Glycyrrhiza glabra leaves, and 170 ppm butyrate salt on the productive performance of broiler chicken was investigated.

[0074] All plant materials came from cultivation. Cultivation and drying followed Good Agricultural and Collecting practices. The dried leaves were grinded to a particle size of < 0.3 mm.

[0075] Diets, fed in mash form, were provided by age of bird: Starter feed fed from 0 day to 14 days, Grower feed fed from 15 days to 28 days and Finisher feed fed from 29 days to 42 days. The basal diets compositions were the following, expressed in kg / 100kg.

[0076] The experimental treatments were made as follow. The Control treatment birds received basal Starter feed, basal Grower feed and basal Finisher feed. The treatment birds received the basal diets, supplemented with 620 ppm of the mixture recited above.

[0077] Each experiment treatment was assigned to 12 pens per treatment.

[0078] Each pen (dimensions of each pen are 4' X 5') contained 1 water fountain and a feed tube. Birds started on wood shavings. 34 Ross 308 day 0 chicks were allocated to each pean. Birds were distributed to pens on day 1 so that equal distribution of birds by body weight among all the study pens. Continuous lighting was provided 0 d to 42 days.

[0079] All broilers were weighed by pen when bird ages are 0, 14, 28 and 42d. Feed was weighed in as needed and weighed out when birds are weighed. The following data were collected during the study: broiler body weights and feed intakes at day 14, day 28 and day 42. These data was collected to calculate feed conversion at day 42 (abbreviated FCR), obtained for a pen as the total feed consumed divided by (sum of total of all body weight for the pen + sum total of all mortality weight for the pen). Adjusted feed conversion ratio with final BW adjustment at day 42 (abbreviated BW42 adjusted FCR) was calculated as follows: Feed conversion + (2.22 kg - actual body weight) 1 7.

[0080] The results are presented in Table 1. Bodyweight at day 42, FCR and BW42 adjusted FCR were improved for the treatment relative to the control.

[0081] Table 1. Results for control vs treatment. Example 2.

[0082] In this example, the effect of 250 ppm dietary inclusion of dried Rubus fruticosus leaves, 16 ppm dried Satureja hortensis aerial parts, 132 ppm dried Artemisia vulgaris aerial parts, 52 ppm dried Glycyrrhiza glabra leaves, and 170 ppm butyrate salt on performance and health of broiler chickens challenged with Enterococcus cecorum was investigated.

[0083] At DO, 20 birds (ROSS 308 broilers; hatching eggs acquired from a commercial hatchery; on-farm hatching was used to reduce hatchery contamination risks) were housed per pen and an Enterococcus inoculum was administered to all birds receiving a challenge. Birds in the challenged groups were subjected to higher temperature than recommended based on the guidelines for ROSS 308 broilers, in order to induce gut leakage. Additionally, feed was not provided for the first 24h, to facilitate the Enterococcus infection.

[0084] Table 2 shows the 4 treatment groups that were used in a commercial farm setting. 6 replicates were used per treatment, and each replicate contained 20 birds.

[0085] Table 2. Treatment details.

[0086] 1Product contained 250 ppm dried Rubus fruticosus leaves, 16 ppm dried Satureja hortensis aerial parts, 132 ppm dried Artemisia vulgaris aerial parts, 52 ppm dried Glycyrrhiza glabra leaves, and 170 ppm butyrate salt.

[0087] 2Challenge: Oral challenge DO with pathogenic Enterococcus cecorum strain; moderate heat stress D0- D7 to increase translocation.

[0088] Results

[0089] Treatment with the product improved recovery after a pathogenic Enterococcus cecorum challenge. The number of positive organ samples (= detection of translocated pathogenic E. cecorum) was reduced in groups receiving treatments 3 and 4, i.e., the groups receiving the product under study. Due to the facility design (commercial farm, adapted to run trials) cross contamination of group 3 with E. cecorum was observed. However, this was likely to happen (as would be the case in field conditions). Group 3 may be considered field- challenged (a couple of days after the oral inoculation).

[0090] Significant (p=0.047 at d42) improvements of body weight were observed when birds were treated with the product compared to their unchallenged and challenged counterparts (Table 3). Table 3. Body weights of the birds receiving the various treatments at d 14, d28, d35 and d42.

[0091] 1As set forth in Table 2: Treatments 2 and 4: challenged; treatments 1 and 3 non-challenged; Treatments 3 and 4: received product.

[0092] Gut health / gut damage

[0093] Gut samples from treatments 1 and 3 (no challenge; without and with treatment with the product) on d14 (age when the microbiome is stabilized in broiler chickens) and d28 (after / during the usual coccidiosis and subclinical NE challenge) were analysed for total bacterial DNA (gut damage assay), number of butyrate-producing microbes, and number of lactate-producing microbes.

[0094] An improvement in the gut damage assay score over time for birds treated with the product was observed. PRC CT data showed that the improvement stemmed from an increase in bacterial DNA between D14 and D28 in birds treated with the product. Higher levels of microbial DNA are considered a beneficial effect of the product and are correlated with high performance.

[0095] Moreover, an significant increase in the number of butyrate-producing bacteria and lactate- producing bacteria in the microbiome was seen in the group treated with the product, which was a significant improvement versus the untreated group.

[0096] Thus, in high performing unchallenged animals, a clear and highly significant positive effect of the product on the host microbiome was observed. As the product is targeting hostmechanisms and not microflora, the observed response of the microbiome is most likely due to successful physiological modulation of a healthy animal into an even more efficient (even healthier) animal.

Claims

CLAIMS1. Composition comprising Satureja hortensis aerial parts, or an extract thereof, Glycyrrhiza glabra aerial parts, or an extract thereof, preferably Glycyrrhiza glabra leaves, or an extract thereof, Artemisia vulgaris aerial parts, or an extract thereof, Rubus fruticosus leaves, or an extract thereof, and a source of butyrate.

2. Composition according to claim 1 , wherein the Satureja hortensis aerial parts, the Artemisia vulgaris aerial parts, the Glycyrrhiza glabra aerial parts, e.g., Glycyrrhiza glabra leaves, and / or the Rubus fruticosus leaves are dried, and optionally ground.

3. Composition according to any one of claims 1 or 2, wherein the extract is selected from the group consisting of an aqueous extract, ethanolic extract, methanolic extract, isopropanolic extract, ethylacetate extract, acetonic extract, hexane extract, a supercritical CO2 extract, or a combination of any of these.

4. Animal feed comprising a composition according to one or more of claims 1-3.

5. Animal feed according to claim 4, comprising said composition in an amount of about 5 to about 10000 mg / kg feed.

6. Use of a composition according to any one of claims 1-3 as a feed additive.

7. Use of a composition according to any one of claims 1-3 or an animal feed according to claim 4 or 5 for improving performance of animals.

8. Use of a composition according to any one of claims 1-3 or an animal feed according to claim 4 or 5 for increasing feed efficiency.

9. Use according to any one of claims 6-8, wherein the feed additive is intended for inclusion in feed for farming animals or companion animals.

10. Use according to any one of claims 7-9, wherein the animal is selected from farming animals and companion animals.

11. Use according to claim 10, wherein the farming animals are selected from the group consisting of poultry, swine, ruminants, e.g., beef cattle and dairy cattle, fish, e.g. salmon, trout, seabream, sea brass, tilapia, tuna, and the like, and crustaceans, e.g., shrimp.

12. Use according to claim 10, wherein the companion animals are selected from the group consisting of ornamental fish, cats, dogs, horses, rabbits, guinea pigs, and hamsters.

13. A method of feeding an animal, said method comprising the step of administering to said animal an animal feed according to any one of claims 4 or 5.

14. Composition according to any one of claims 1-3 or an animal feed according to any one of claims 4-5 for use as a medicament.

15. Composition for use in preventing and / or reducing infection, e.g., microbial infection, and / or diseases caused by such infection, e.g., microbial infection, in an animal.

16. A composition for use according to claim 15, wherein the microbe is selected from the group consisting of a fungus, a yeast, a virus, a parasite, a Gram-positive bacterium, and a Gram-negative bacterium.

17. A composition for use according to claim 16, wherein the microbe is selected from the group consisting of a Gram-negative and a Gram-positive bacterium.

18. A composition for use according to claim 17, wherein the microbe is a Gram-positive bacterium, preferable of the genus Enterococcus, such as from the species E. avium, E. gallinarum and E. cecorum.

19. A composition for use according to any one of claims 15-18, wherein the disease is selected from the group consisting of enterococcosis, coccidiosis, sepsis, and spondylitis.

20. A method of inhibiting translocation of pathogenic microbes such as Enteroccocus spp.in an animal, said method comprising administering to said animal a composition according to any one of claims 1-3 or animal feed according to claims 4 or 5.

21. A method of improving gut health and / or preventing gut damage, said method comprising the step of administering to said animal a composition according to any one of claims 1-3 or animal feed according to claims 4 or 5.

22. A method according to claim 21, wherein the number of butyrate-producing microbes and / or lactate-producing microbes are increased in the gut.

Images