Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan in the prevention or treatment of diseases associated with or caused by Rhodotorula intracellaris infection

Abstract

The present invention discloses a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan for use in the prevention or treatment of diseases associated with Lawsonia intracellularis infection or diseases caused by Lawsonia intracellularis infection. The present invention relates to a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan for use in the prevention or treatment of diseases associated with Lawsonia intracellularis infection or diseases caused by Lawsonia intracellularis infection in pigs, which contains β-glucan and mannan, wherein the β-glucan is in the form of a mixture of β-1,3-glucan and β-1,6-glucan and is present in a total amount of 50% by weight or more, particularly 50% to 99% by weight, and the mannan is present in a total amount of less than 5% by weight, particularly 1% to 5% by weight.

Description

Technical Field

[0001] The present invention relates to the field of health, and more specifically, to the field of animal health. More specifically, the present invention relates to a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan and its use in the prevention or treatment of diseases associated with Lawsonia intracellularis infection or diseases caused by Lawsonia intracellularis infection in pigs.

Background Art

[0002] Lawsonia intracellularis, an obligate Gram-negative intracellular bacterium, is the pathogen of porcine ileitis. Ileitis, also known as proliferative enteropathy, is one of the most frequently seen digestive diseases affecting growing and finishing pigs worldwide.

[0003] The characteristic pathological feature of the disease is the proliferation of immature epithelial cells in the crypts of the ileum (the terminal part of the small intestine), the large intestine, or both. Some of the infected tissues are characterized by red and thickened mucosa, a "hose"-like state, and intestinal lesions. When the intestine thickens, it ultimately inhibits the normal function of the intestine, absorption capacity, and nutrient transfer. The clinical effects of the disease include chronic weight loss, anorexia, diarrhea, and ultimately death.

[0004] The disease occurs in acute or chronic forms. The chronic form mainly affects pigs aged 6 to 20 weeks, and the clinical symptoms are rather unclear, i.e., a decrease in growth ability such as a daily decrease in weight gain, with or without diarrhea. Therefore, the disease is often not detected. The acute form is characterized by bloody stools and sudden death and affects pigs aged 4 to 12 months. In infected pig herds, the disease causes significant economic losses to livestock farmers due to a decrease in technical productivity, an increase in drug costs, and an increase in induced mortality.

[0005] Currently, various vaccination strategies are available for combating ileitis. The strategies generally involve parenterally administering (e.g., injecting) the vaccine to young pigs. However, this approach is not entirely satisfactory as it is relatively cumbersome for livestock farmers.

[0006] Therefore, there is a real need to develop new methods for the prevention and / or treatment of diseases associated with Lawsonia intracellularis infection, such as ileitis in animals, particularly pigs, or diseases caused by Lawsonia intracellularis infection. SUMMARY OF THE INVENTION

[0007] The inventors have surprisingly discovered that a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan significantly enhances the immunity of pigs exposed to Lawsonia intracellularis, thereby providing a means for preventing and / or treating infections caused by the Lawsonia intracellularis bacteria, and / or diseases associated with or caused by said bacteria, particularly ileitis.

[0008] More specifically, the inventors have demonstrated that by treating pigs exposed to Lawsonia intracellularis with a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan according to the present invention, it is possible to promote the weight gain of pigs and reduce the incidence of infection within the pig population.

[0009] Furthermore, unlike parenteral vaccination strategies, a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan is advantageous for oral administration, particularly feed administration, and can act more directly in the intestine where pathogens are mainly present.

[0010] Accordingly, an object of the present invention is to contain β-glucan and mannan, The β-glucan is in the form of a mixture of β-1,3-glucan and β-1,6-glucan and is present in a total amount of 50% by weight or more, particularly 50% to 99% by weight. The mannan is present in a total amount of less than 5% by weight, particularly 1% to 5% by weight, and relates to the use of a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan for the prevention or treatment of diseases associated with Rhodotorula intracellaris infection or diseases caused by Rhodotorula intracellaris infection in pigs.

[0011] In certain embodiments, the disease is an inflammatory bowel disease, particularly ileitis.

[0012] In certain embodiments, the total amount of the β-glucan present in the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan is 50% to 90% of the weight of the extract, for example, 50% to 80%, 50% to 70%, or actually 50% to 60% of the weight of the extract.

[0013] In certain embodiments, the total amount of the mannan present in the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan is 2% to 4% of the weight of the extract.

[0014] In certain embodiments, the amount of the mannan in the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan is such that the β-glucan / mannan ratio is 12 to 40 (weight / weight).

[0015] In certain embodiments, the amount of the mannan in the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan is such that the β-glucan / mannan ratio is 15 to 30 (weight / weight), particularly 18 to 22 (weight / weight).

[0016] In certain embodiments, a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan is characterized by containing a dry matter content of 94% by weight or more, particularly 96% by weight or more.

[0017] In certain embodiments, a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan further comprises a protein content of 10% by weight or less and a glycogen content of 10% by weight or less.

[0018] In certain embodiments, in a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan, the β-glucan and mannan are the only active ingredients of the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan.

[0019] In certain embodiments, the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan is actually Safglucan® containing β-glucan and mannan. The β-glucan is present in the form of a mixture of β-1,3-glucan and β-1,6-glucan, with a total amount of 52% to 60% by weight, and the mannan is present with a total amount of 1% to 5% by weight. The Safglucan® further comprises a protein content of 10% by weight or less and a glycogen content of 10% by weight or less.

[0020] In a second aspect, the present invention relates to a composition comprising a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan and at least one bioactive agent for use in the prevention of infectious diseases associated with the bacterium Lawsonia intracellularis in pigs, wherein the extract is as defined in this patent specification.

[0021] In certain embodiments, the bioactive agent is selected from the group consisting of antibiotics, vaccines, probiotics, prebiotics, vitamins, minerals, trace elements, and mixtures thereof.

[0022] In a third aspect, the object of the present invention is a pharmaceutical composition for use in the prevention or treatment of infectious diseases associated with bacterial Lawsonia intracellularis in pigs, comprising a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan and at least one physiologically acceptable excipient, wherein the extract is as defined herein, and relates to a pharmaceutical composition characterized by this.

[0023] In a fourth aspect, the object of the present invention is a pig feed comprising a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan for use in the prevention of diseases associated with Lawsonia intracellularis infection in pigs or diseases caused by Lawsonia intracellularis infection, wherein the extract is as defined herein or is part of a composition as defined herein, and relates to a pig feed characterized by this.

Brief Description of the Drawings

[0024]

Figure 1

Figure 2

Figure 3

Modes for Carrying Out the Invention

[0025] The present invention will be described in more detail and non - limitatively in the following description.

[0026] Unless otherwise specified, all percentages regarding quantities are weight percentages.

[0027] As described above, the present invention contains β - glucan and mannan, β-glucan is present in the form of a mixture of β-1,3-glucan and β-1,6-glucan, and is present in a total amount of 50% by weight or more, particularly 50% to 99% by weight. Mannan is present in a total amount of less than 5% by weight, particularly 1% to 5% by weight. It relates to a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan for use in the prevention or treatment of diseases associated with Rhodotorula intracellaris infection or diseases caused by Rhodotorula intracellaris infection in animals, particularly pigs.

[0028] In certain embodiments, the animals to which the present invention is applied are animals selected from among livestock and pets, and particularly pigs or horses.

[0029] Therefore, all extracts, compositions, pharmaceutical compositions, and feeds that constitute the subject matter of the present invention and are described below with respect to pigs are also applicable to other animal species, particularly horses.

[0030] As used herein, the term "pig" generally refers to animal species of the family Suidae.

[0031] As used herein, the term "horse" generally refers to the family Equidae.

[0032] The term "disease associated with Rhodotorula intracellaris infection, or disease caused by Rhodotorula intracellaris infection" refers to diseases that are indirectly ("associated with") or directly ("caused by") related to Rhodotorula intracellaris infection.

[0033] <I. Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan> The β-glucan of the extract according to the present invention is obtained from Saccharomyces cerevisiae yeast, more specifically from a Saccharomyces cerevisiae yeast strain. The state-of-the-art technology includes many known strains of Saccharomyces cerevisiae. These known strains are widely used in the agro-food industry to play their role in the production of various foods, most notably breads and fermented beverages.

[0034] As used herein, the term "yeast strain" refers to a relatively homogeneous population of yeast cells obtained by culturing (or propagating) a starter strain. A yeast strain is obtained from a clone, which is a population of yeast cells obtained from a single yeast cell. The Saccharomyces cerevisiae yeast strain may be cultured using any suitable method. Methods for culturing yeast are known in the prior art, and those skilled in the art know how to optimize the culture conditions based on the properties of each strain. Thus, Saccharomyces cerevisiae yeast may be obtained, for example, by culturing the strain in a suitable culture medium as described in the reference book "Yeast Technology", 2nd Edition, 1991, G. Reed and T. W. Nagodawithana, published by Van Nostrand Reinhold, ISBN 0-442-31892-8.

[0035] In this specification, the terms "yeast cell wall" and "yeast hull" are used interchangeably and refer to the insoluble fraction of yeast cells, i.e., the wall and cell membrane of yeast. In the conventional method, the yeast cell wall is obtained by a method including an essentially self-digestion step with protease or an enzymatic hydrolysis step followed by a separation step of separating a soluble fraction from the insoluble fraction, and the separated insoluble fraction corresponds to the yeast cell wall. Thereafter, the insoluble fraction can be dried. The production method for obtaining the yeast cell wall is a method that retains the structural polysaccharides of the cell wall, i.e., β-glucan and mannan, and these mannans are in the form of mannoproteins. The production method for obtaining the yeast cell wall is known in the art (for example, see the reference book "Yeast Technology", 2nd Edition, 1991, G. Reed and T. W. Nagodawithana, published by Van Nostrand Reinhold, New York, ISBN 0-442-31892-8).

[0036] The Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan according to the present invention refers to a fraction mainly containing β-glucan extracted (or isolated) from the cell wall. The β-glucan derived from the yeast cell wall is called "cell wall β-glucan". β-glucan is essentially a glucose polymer in which the glucose units of the main chain are linked by β-1,3 bonds and the branches are linked by β-1,6 bonds. Yeast β-glucan is insoluble and has a low viscosity. A person skilled in the art knows the method of extracting β-glucan from the yeast cell wall. A general method includes successive high-temperature extraction with a base and an acid (such as acetic acid), followed by washing with water to remove any soluble compounds from the cell wall, and recovery of the insoluble substance consisting of cell wall β-glucan.

[0037] The Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan according to the present invention contains β-glucan in the form of a mixture of β-1,3-glucan and β-1,6-glucan, and contains β-glucan with a total amount of 50% by weight or more. As used herein, the term "the total amount of β-glucan is 50% by weight or more" indicates that β-glucan occupies at least half of the weight of the extract according to the present invention. Therefore, the total amount of β-glucan present in the extract according to the present invention may represent 50% to 90% of the weight of the extract, for example, 50% to 80%, 50% to 70%, or actually 50% to 60% of the weight of the extract.

[0038] In certain embodiments, the total amount of β-glucan present in the extract according to the present invention represents 50% to 65% of the weight of the extract, for example, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, or about 65%.

[0039] The Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan according to the present invention also contains mannan with a total amount of less than 5% by weight. Mannan obtained from yeast cell walls is called "cell wall mannan". Mannan is a yeast polysaccharide mainly composed of mannose, more precisely a copolymer of neutral or acidic aoses (5 or 6 carbon atoms), linked to each other by glycosidic bonds and bound to proteins. In Saccharomyces cerevisiae cell wall mannan, mannose exists in the form of a backbone of α-(1,6)-linked mannose residues (50 or more), branched by short chains of α-(1,2)- and α-(1,3)-linked mannose. Those skilled in the art know methods for extracting mannan from yeast cell walls. A common method includes the steps of enzymatically digesting yeast cell walls using a β-glucanase preparation (for example, the industrial preparation GLUCANEX®), subsequently separating the hydrolyzate by centrifugation, and purifying it by ultrafiltration. Another method is based on high-temperature chemical extraction.

[0040] As used herein, the term "total amount of mannan is less than 5% by weight" means that mannan represents up to 5% of the weight of the extract according to the present invention. Thus, the total amount of mannan present in the extract according to the present invention may represent 0.5% to 5% of the weight of the extract, particularly 0.5% to 1.5% of the weight of the extract.

[0041] Preferably, the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan according to the present invention contains β-glucan and mannan, the β-glucan is present in the form of a mixture of β-1,3-glucan and β-1,6-glucan in a total amount of 50% by weight or more, and the mannan is present in a total amount such that the β-glucan / mannan ratio is 12 to 40 (weight / weight). In particular, the β-glucan / mannan ratio in the extract according to the present invention may be 15 to 30 (weight / weight), more specifically 18 to 22 (weight / weight).

[0042] In certain embodiments, the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan according to the present invention further contains protein with a content of 10% by weight or less and glycogen with a content of 10% by weight or less.

[0043] In certain embodiments, the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan according to the present invention contains β-glucan and mannan as the only active ingredients, and the β-glucan is present in the form of a mixture of β-1,3-glucan and β-1,6-glucan in a total amount of 50% by weight or more, and the mannan is present in a total amount of less than 5% by weight, such that the β-glucan / mannan ratio is 12 to 40 (weight / weight), particularly 15 to 30 (weight / weight), more particularly 18 to 22 (weight / weight).

[0044] In certain embodiments, the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan according to the present invention contains a dry matter with a content of 94% by weight or more, preferably 96% by weight or more. When the content of the dry matter is 94% by weight or more, preferably 96% by weight, the preservability of the yeast shell is improved, particularly the bacteriological stability is improved, and the stability against undesirable reactions of enzymatic or non-enzymatic origin is improved.

[0045] In certain embodiments, the Saccharomyces cerevisiae yeast cell wall extract according to the present invention is in powder form.

[0046] In certain embodiments, the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan according to the present invention is Safglucan® manufactured by the applicant, Rousselot. Safglucan® contains β-glucan and mannan as the only active ingredients. The β-glucan is present in the form of a mixture of β-1,3-glucan and β-1,6-glucan, with a total amount of 52% to 60% by weight, and the mannan is present with a total amount of 1% to 5% by weight. Safglucan® further contains a protein with a content of 10% by weight or less and glycogen with a content of 10% by weight or less.

[0047] The Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan according to the present invention may generally be dried, and packaged and / or stored under appropriate conditions in a cool place after production and before use. The shelf life of the cell wall extract according to the present invention is two years from the production date in the case of appropriate packaging.

[0048] <II. Composition Containing Saccharomyces cerevisiae Yeast Cell Wall Extract Rich in β-Glucan> In certain embodiments, the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan described herein is used as it is, particularly without the presence of other active substances.

[0049] In other embodiments, the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan described herein is used in combination with at least one other bioactive agent. Accordingly, the present invention relates to a composition comprising a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan described herein and at least one bioactive agent.

[0050] As indicated herein, the term "bioactive agent" refers to an agent beneficial to the health of animals. The bioactive agent may be a veterinary active substance having a therapeutic or prophylactic effect. The bioactive agent may be selected, for example, from among antibiotics, vaccines, probiotics, prebiotics, or mixtures thereof.

[0051] In certain embodiments, the bioactive agent is selected from among antibiotics, vaccines, or prebiotics.

[0052] In particular, the bioactive agent does not include probiotics, especially microbial pesticides such as Bacillus subtilis strain QST-713.

[0053] In an extended sense, the term "bioactive agent" further refers to substances having beneficial effects from a nutritional perspective, especially nutrients such as vitamins, minerals, trace elements, and substances commonly included in animal supplements, adjuvants, and feed additives.

[0054] A person skilled in the art knows how to select appropriate components according to the animal (in this case, pigs) targeted by the composition, and also knows how to determine the appropriate amounts contained in such a composition.

[0055] The composition according to the present invention may be in any form, such as in the form of a powder, granule, gel, or liquid. Preferably, the composition according to the present invention is in a solid form, preferably in a powder form.

[0056] The present invention further relates to a pharmaceutical composition comprising a Saccharomyces cerevisiae yeast cell wall extract rich in the β-glucan described herein and at least one physiologically acceptable excipient used in veterinary medicine. In the pharmaceutical composition, the extract may be present as the sole active ingredient. Alternatively, the pharmaceutical composition may further comprise at least one other bioactive agent, such as those listed above.

[0057] The pharmaceutical composition according to the present invention may be classified as a veterinary pharmaceutical formulation available in a prescription or commercially.

[0058] In the present invention, the term "physiologically acceptable excipient used in veterinary medicine" refers to any medium or additive that, at the administered concentration, does not interfere with the biological activity of the active ingredient (in this case, the cell wall extract rich in β-glucan) and is not overly toxic to animals.

[0059] The veterinary pharmaceutical composition according to the present invention may be administered using any combination of an effective dosage and an administration route to achieve the desired prophylactic effect. Preferably, the pharmaceutical composition is administered via the oral route. One skilled in the art will recognize that the exact amount to be administered to a pig may vary depending on the weight of the animal and the effect of Lawsonia intracellularis on the animal being treated.

[0060] <III. Use of a Saccharomyces cerevisiae yeast cell wall extract rich in dried β-glucan> As described above, Lawsonia intracellularis infection in pigs causes intestinal inflammation, particularly ileitis, leading to diarrhea and in some cases sudden death. As a result of these infections, both the feed efficiency and weight gain of the animals are reduced.

[0061] The Saccharomyces cerevisiae yeast cell wall extract rich in the β-glucan described herein has been shown to significantly reduce the symptoms associated with Lawsonia intracellularis infection.

[0062] Accordingly, the present invention also relates to a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan as described herein for use in the prevention or treatment of Lawsonia intracellularis infection in pigs, either alone or in combination with at least one bioactive agent.

[0063] Accordingly, the present invention also relates to a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan as described herein for use in the prevention or treatment of diseases associated with Lawsonia intracellularis infection or diseases caused by Lawsonia intracellularis infection in pigs, either alone or in combination with at least one bioactive agent.

[0064] Diseases associated with Lawsonia intracellularis or diseases caused by Lawsonia intracellularis may be intestinal inflammations selected from the group consisting of intestinal inflammation, particularly enteritis or ileitis.

[0065] Accordingly, the present invention also relates to a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan as described herein for use in the prevention or treatment of inflammatory bowel diseases in pigs, particularly diseases associated with Lawsonia intracellularis infection such as ileitis or diseases caused by Lawsonia intracellularis infection, either alone or in combination with at least one bioactive agent.

[0066] As used herein, the term "prevention" refers to an act aimed at preventing or delaying the onset of a disease, and in particular, an act aimed at partially or wholly reducing or suppressing the possibility that one or more symptoms (such as diarrhea, weight loss, intestinal wall thickening, etc.) related to a disease associated with Ralstonia intracellularis infection or a disease caused by Ralstonia intracellularis infection occur in a subject. The terms "prevention" and "preventive treatment" are synonymous and may be used interchangeably in the context of the present invention. Prevention is not only targeted at subjects having a constitution prone to infectious diseases, preferably intestinal infectious diseases, but also at subjects not having such a constitution to a great extent.

[0067] As used herein, the term "treatment" refers to any act aimed at improving the medical condition of a subject suffering from a disease. Treatment may be aimed at improving the patient's medical condition, i.e., alleviating the disease or a specific symptom thereof, or eradicating the disease or a specific symptom thereof. The treatment may also have the effect of preventing or delaying the progression of the disease.

[0068] In some embodiments of the present invention, the extract or composition is intended to be used for the prevention of a disease associated with Ralstonia intracellularis in pigs or a disease caused by Ralstonia intracellularis.

[0069] In a specific embodiment of the present invention, using a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan, alone or in combination with at least one bioactive agent, for the prevention of a disease associated with the bacterium Ralstonia intracellularis or a disease caused by the bacterium Ralstonia intracellularis includes the step of mixing the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan with an animal feed. The mixing may be performed by any suitable method known in the art.

[0070] As used herein, the terms "animal feed," "animal feed ingredient," and "animal feed product" refer to natural or processed organic materials that are readily biodegradable and suitable for ingestion by animals. Examples of such organic materials range from freshly harvested grains to pelletized feeds and include, for example, compounds, grains, nuts, feeds, silages, formulations, compositions, or mixtures that are suitable for, or intended for, ingestion by animals. Animal feed may be in the form of pellets, liquids, slurries, or so-called "mash feeds."

[0071] The term "feed" refers to plant material (mainly the leaves and stems of plants) eaten by herbivores. The term "silage" refers to a fermented feed with a high moisture content suitable for use as feed for ruminants. Formulations, compositions, and mixtures, such as commercially available formulations, compositions, and mixtures, may be in suitable forms such as concentrates, premixes, supplements, total mixed rations (TMR), etc. Animal feed may include grains (corn, wheat, barley, rye, rice, sorghum, millet, or combinations thereof), feeds, silages, legumes (such as soybeans), brewing by-products, animal products, etc. Brewing by-products are mainly obtained from the processing of corn, wheat, barley, rye, rice, sorghum, millet, or combinations thereof. Brewing by-products are mainly produced as a result of industrial processes such as brewing and distillation for the production of drinking alcohol (whiskey, vodka, gin) or biofuels. Beer grains are produced from malt, and malt is produced from barley. In Africa in particular, grains other than barley, such as sorghum, may be used for brewing. Brewing by-products resulting from bioethanol production are obtained from corn or wheat. Wet brewing by-products are dried to produce dried brewing by-products that are mainly used as animal feed.

[0072] The Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan described in this specification may be added to animal feed in an amount of about 0.02% to about 0.05% of the total weight of the feed (corresponding to an amount of about 200 g to about 500 g per ton of feed), provided that it complies with the current applicable laws, either alone or in combination with at least one bioactive agent. For example, in certain embodiments, the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan described in this specification is added to animal feed in an amount of about 0.02% to about 0.05% of the total weight of the feed (corresponding to an amount of about 200 g to about 500 g per ton of feed), for example, added to animal feed in an amount of about 0.02% to about 0.05% by weight of the feed (corresponding to an amount of about 200 g to about 500 g per ton of feed).

[0073] The extract or composition according to the present invention may be administered throughout the entire period of infection or throughout the entire period of the risk of infection. In particular, the extract or composition may be continuously administered with the feed for the purpose of preventing diseases associated with the bacterium Rhodococcus equi or diseases caused by the bacterium Rhodococcus equi, and / or Rhodococcus equi bacterial infections.

[0074] Unless otherwise defined, all technical and scientific terms used herein have the same significance / meaning as commonly understood by one of ordinary skill in the art to which the present invention pertains.

Examples

[0075] The following examples illustrate specific embodiments of the present invention. However, it will be understood that the examples and figures are presented for illustrative purposes only and are not intended to limit the scope of the present invention.

[0076] <Materials and Methods> 160 piglets (Duroc x Hampshire) were obtained from a commercial farm and placed in a finishing / finisher unit where Rhodococcus intracellularis bacteria were present. Upon arrival at the farm, the piglets were individually weighed and ear-tagged. Next, the animals were divided into two groups of 80 pigs each (one control group and one treatment group). The animals were then further divided into subgroups of 10 pigs each. The control group was fed a standard diet. The treatment group was fed a normal diet containing a beta-glucan product (250 ppm) throughout the test period. The animals in both groups were weighed on days 63, 81, and 97, and feces were collected and tested for the presence of Rhodococcus intracellularis bacteria by quantitative qPCR.

[0077] <Results> The results showed that, 97 days after the start of treatment, the treated animals had an average weight gain of approximately 5 kg compared to the control group (Figures 1 and 2).

[0078] The presence of Rhodococcus intracellularis in the feces was significantly reduced (Figure 3).

Claims

**Claim 1** Comprising β-glucan and mannan, wherein the β-glucan is in the form of a mixture of β-1,3-glucan and β-1,6-glucan and is present in a total amount of 50% by weight or more, particularly 50% to 99% by weight, and the mannan is present in a total amount of less than 5% by weight, particularly 1% to 5% by weight, and is used for the prevention or treatment of diseases associated with Rhodotorula intracellaris infection in pigs or diseases caused by Rhodotorula intracellaris infection. A Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan. **Claim 2** The disease is an inflammatory bowel disease, particularly ileitis. A Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan for use in the prevention or treatment of diseases associated with Rhodotorula intracellaris infection in pigs or diseases caused by Rhodotorula intracellaris infection according to claim 1. **Claim 3** The total amount of the β-glucan present in the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan is 50% to 90% of the weight of the extract, for example, 50% to 80%, 50% to 70%, or actually 50% to 60% of the weight of the extract. A Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan for use in the prevention or treatment of diseases associated with Rhodotorula intracellaris infection in pigs or diseases caused by Rhodotorula intracellaris infection according to claim 1 or 2. **Claim 4** The total amount of the mannan present in the Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan is 2% to 4% of the weight of the extract. A Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan for use in the prevention or treatment of diseases associated with Rhodotorula intracellaris infection in pigs or diseases caused by Rhodotorula intracellaris infection according to any one of claims 1 to 3. **Claim 5** The amount of the mannan in the Saccharomyces cerevisiae yeast cell wall extract rich in the β-glucan is an amount such that the β-glucan / mannan ratio is 12 to 40 (weight / weight), for use in the prevention or treatment of a disease associated with Rhodococcus intracellularis infection or a disease caused by Rhodococcus intracellularis infection in pigs according to any one of claims 1 to 4, a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan.

6. The amount of the mannan in the Saccharomyces cerevisiae yeast cell wall extract rich in the β-glucan is an amount such that the β-glucan / mannan ratio is 15 to 30 (weight / weight), particularly 18 to 22 (weight / weight), for use in the prevention or treatment of a disease associated with Rhodococcus intracellularis infection or a disease caused by Rhodococcus intracellularis infection in pigs according to any one of claims 1 to 5, a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan.

7. Characterized in that it contains a dry matter with a content of 94% by weight or more, particularly 96% by weight or more, for use in the prevention or treatment of a disease associated with Rhodococcus intracellularis infection or a disease caused by Rhodococcus intracellularis infection in pigs according to any one of claims 1 to 6, a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan.

8. Further comprising a protein with a content of 10% by weight or less and glycogen with a content of 10% by weight or less, for use in the prevention or treatment of a disease associated with Rhodococcus intracellularis infection or a disease caused by Rhodococcus intracellularis infection in pigs according to any one of claims 1 to 7, a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan.

9. The β-glucan and mannan are the sole active ingredients of a Saccharomyces cerevisiae yeast cell wall extract rich in the β-glucan, and are used for the prevention or treatment of a disease associated with Lawsonia intracellularis infection in pigs or a disease caused by Lawsonia intracellularis infection, and are characterized by being a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan according to any one of claims 1 to 8.

10. It is Safuglucan (registered trademark) containing β-glucan and mannan. The β-glucan exists in the form of a mixture of β-1,3-glucan and β-1,6-glucan, with a total amount of 52 to 60% by weight. The mannan exists with a total amount of 1 to 5% by weight. The Safuglucan (registered trademark) further contains a protein with a content of 10% by weight or less and glycogen with a content of 10% by weight or less, and is characterized by being a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan for the use according to claim 9.

11. A composition comprising a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan and at least one bioactive agent for use in the prevention of an infectious disease associated with the bacterium Lawsonia intracellularis in pigs, wherein the extract is as defined in any of claims 1 to 10, and is characterized by being such a composition.

12. The bioactive agent is selected from the group consisting of antibiotics, vaccines, probiotics, prebiotics, vitamins, minerals, trace elements, and mixtures thereof, according to the composition of claim 11.

13. A pharmaceutical composition comprising a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan and at least one physiologically acceptable excipient for use in the prevention or treatment of an infectious disease associated with the bacterium Lawsonia intracellularis in pigs, wherein the extract is as defined in any of claims 1 to 10, and is characterized by being such a pharmaceutical composition.

14. A swine feed containing a Saccharomyces cerevisiae yeast cell wall extract rich in β-glucan for use in the prevention of diseases associated with Lawsonia intracellularis infection or diseases caused by Lawsonia intracellularis infection in swine, wherein the extract is as defined in any of claims 1 to 9 or is part of a composition as defined in claim 11 or 12, characterized in that it is a swine feed.

Images