Feed additive composition for improving intestinal health of livestock and poultry and application thereof

Abstract

The present invention relates to the technical field of feed additives, and in particular to a feed additive composition for improving the intestinal health of livestock and poultry and its application. The feed additive composition provided by the present invention comprises the following components in parts by weight: 25-65 parts of ursolic acid, 1-10 parts of oligosaccharides, 1-15 parts of chlorogenic acid compounds, and 1-15 parts of sesquiterpenoid compounds. The feed additive composition can significantly increase the height of the villi in the small intestine of livestock and poultry, reduce the depth of the crypts, and significantly increase the villus-crypt ratio, thereby effectively improving the intestinal morphology. It can also effectively regulate the intestinal microbial population of livestock and poultry, improve intestinal health, promote the growth of livestock and poultry, and improve the immunity of livestock and poultry. It can be used as a safe, efficient, stable, and controllable green and environmentally friendly feed additive.

Description

Technical Field

[0001] The present invention relates to the technical field of feed additives, and in particular to a feed additive composition for improving the intestinal health of livestock and poultry and applications thereof. Background Art

[0002] The intestine is not only the primary site for nutrient digestion and absorption, but also a crucial secretory and immune organ, with a crucial defensive function. Therefore, intestinal health is crucial to livestock and poultry production. Villus villi, a crucial component of the intestine, have a morphological structure that directly influences the body's digestion and absorption of nutrients. Villus height, crypt depth, and the ratio of villus height to crypt depth (villus-crypt ratio) are important indicators for evaluating the digestive and absorptive capacity of the intestine.

[0003] The intestinal flora is composed of a large number of microorganisms and is a self-stable equilibrium. The proliferation of harmful bacteria in the intestine can disrupt the intestinal microecological balance, produce a large amount of toxic substances, affect the animal's nutritional digestion, metabolism, immunity and health, and cause a decrease in animal growth performance. Members of the Proteobacteria are Gram-negative bacteria, including many pathogens such as Escherichia coli, Salmonella, Vibrio cholerae, Helicobacter pylori, etc. In recent years, the intestinal microbiome of broiler chickens has been widely studied, and it plays an important role in host health and production performance. With the ban on the use of growth-promoting antibiotics, improving the growth and immunity of broiler chickens by regulating the intestinal microbiome has become an effective way to solve the problem of antibiotic substitution.

[0004] With the ban on the use of antibiotics in feed, the risk of broiler chickens developing intestinal bacterial infections, oxidative stress, and necrotic enteritis has greatly increased, seriously impacting the healthy development of the broiler industry. Therefore, the development of feed additive compositions that can replace antibiotics is of great significance for improving the intestinal health of livestock and poultry. Summary of the Invention

[0005] The present invention provides a feed additive composition for improving the intestinal health of livestock and poultry and application thereof.

[0006] Specifically, the present invention provides the following technical solutions:

[0007] The present invention provides a feed additive composition. The composition comprises the following components in parts by weight: 25-65 parts of ursolic acid, 1-10 parts of oligosaccharides, 1-15 parts of chlorogenic acid compounds, and 1-15 parts of sesquiterpenoid compounds.

[0008] In the process of screening feed additive components and their combinations, the present invention unexpectedly discovered that ursolic acid, oligosaccharides, chlorogenic acid compounds, and sesquiterpenoid compounds can play a synergistic role in improving intestinal morphology and health (especially in increasing intestinal villus height, reducing crypt depth and improving villus-crypt ratio) within the above-mentioned ratio range. Under the condition of the same daily dietary addition amount, the combination of ursolic acid, oligosaccharides, chlorogenic acid compounds, and sesquiterpenoid compounds has a significantly higher effect on improving the intestinal morphology and health of livestock and poultry than the effect of adding each component alone.

[0009] Preferably, the oligosaccharide is any one or more selected from fructooligosaccharide, xylooligosaccharide and raffinose.

[0010] The chlorogenic acid compound is any one or more selected from chlorogenic acid, chlorogenic acid derivatives, caffeic acid, caffeic acid derivatives, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C.

[0011] The sesquiterpenoid compound is any one or more selected from sesquiterpenoid alcohols and sesquiterpenoid aldehydes.

[0012] More preferably, the sesquiterpenoid compound is α-solanol.

[0013] When selecting the above substances, it is preferred that the mass ratio of ursolic acid to sesquiterpenoid compounds in the composition is (2-10):1.

[0014] When selecting the above substances, it is preferred that the mass ratio of oligosaccharides to sesquiterpenoids in the composition is 1:(0.5-3).

[0015] When selecting the above substances, it is preferred that the mass ratio of the chlorogenic acid compound to the sesquiterpenoid compound in the composition is (0.5-2):1.

[0016] The present invention has found that ensuring that the components are within the above ratio range is more conducive to the four components in the composition playing a synergistic role in improving the intestinal health of livestock and poultry.

[0017] Preferably, the feed additive composition comprises the following components in parts by weight: 30-60 parts of ursolic acid, 5-10 parts of raffinose, 5-15 parts of isochlorogenic acid C, and 5-15 parts of α-solanol.

[0018] There are many substances known to improve the intestinal health of livestock and poultry. However, existing feed additives usually need to contain many kinds of functional compounds to play a significant role in improving the intestinal health of livestock and poultry. There are also feed additives that play a role by adding plant extracts. However, in addition to the target functional components, plant extracts also contain a large number of substances with known or unknown structures and functions. These substances may have adverse effects on the growth and health of livestock and poultry. The present invention has found that ursolic acid, raffinose, isochlorogenic acid C, and α-chlorogenic acid C have a synergistic effect in improving the morphological structure of the intestine, achieving a feed additive composition with fewer ingredients and a clear composition to significantly improve the intestinal health of livestock and poultry.

[0019] The present invention also provides a method for preparing the feed additive composition described above, comprising: mixing ursolic acid, oligosaccharides, chlorogenic acid compounds, and sesquiterpenoid compounds.

[0020] The present invention also provides use of the above feed additive composition in feed additive or feed preparation.

[0021] The above application in the preparation of feed additives includes: mixing the feed additive composition with other feed additive components to obtain the feed additive, or mixing the feed additive composition with other feed additive components and / or auxiliary materials to obtain the feed additive.

[0022] The above application in feed preparation includes: mixing the feed additive composition with a basic diet feed to obtain feed, or mixing the feed additive composition with a basic diet feed and / or supplementary materials to obtain feed.

[0023] The above-mentioned auxiliary materials can be any auxiliary materials allowed in the feed field.

[0024] The present invention provides a feed comprising the above feed additive composition.

[0025] Preferably, the mass percentage of the feed additive composition in the feed is 0.01-0.1%.

[0026] The present invention provides the above-mentioned feed additive composition or use of the feed in improving the intestinal morphology and / or improving the intestinal microbial composition of livestock and poultry.

[0027] Among them, the improvement of the intestinal morphology of livestock and poultry includes increasing the height of the villi in the intestinal tract of livestock and poultry, reducing the depth of the crypts in the intestinal tract of livestock and poultry and / or increasing the ratio of the height of the villi to the depth of the crypts in the intestinal tract of livestock and poultry.

[0028] The improving of the intestinal microbial composition of livestock and poultry includes increasing the abundance of Firmicutes, decreasing the abundance of Bacteroidetes, increasing the abundance ratio of Firmicutes to Bacteroidetes, and / or decreasing the abundance of Proteobacteria.

[0029] Preferably, the application comprises: administering the feed additive composition or the feed to livestock and poultry, wherein the administration amount of the feed additive composition is 250-750 mg per kilogram of basic diet.

[0030] The present invention provides the use of the above-mentioned feed additive composition or the feed in preparing a product for improving the intestinal morphology and / or improving the intestinal microbial composition of livestock and poultry.

[0031] In the present invention, the livestock and poultry include but are not limited to chickens, ducks, geese, pigs, cattle, sheep, horses and other poultry and livestock.

[0032] Preferably, the livestock and poultry are chickens, including broilers or laying hens.

[0033] The beneficial effects of the present invention are: the present invention has discovered that ursolic acid, oligosaccharides, chlorogenic acid compounds, and sesquiterpenoid compounds have a synergistic effect in improving the intestinal health of livestock and poultry. The combination of these four components as a feed additive composition can significantly increase the height of the villi in the small intestine of livestock and poultry, reduce the depth of the crypts, and significantly increase the villus-crypt ratio, thereby effectively improving the intestinal morphology, improving the intestinal health, enhancing the immunity of livestock and poultry, and improving the growth performance of livestock and poultry.

[0034] The feed additive composition provided by the present invention can also effectively regulate the intestinal microbial population of livestock and poultry, increase the abundance of beneficial intestinal bacteria, reduce the abundance of harmful bacteria, thereby improving intestinal health, promoting the growth of livestock and poultry, and improving the immunity of livestock and poultry.

[0035] The feed additive composition provided by the present invention is beneficial to reducing the use of antibiotics, ensuring the safety of animal products, and can be used as a safe, efficient, stable, controllable, green and environmentally friendly feed additive. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the technical solutions in the present invention or the prior art, a brief introduction will be given below to the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0037] Figure 1 The composition of the caecal microorganisms of broiler chickens at the phylum level in the experimental examples of the present invention, wherein CON represents the control group, and SY1-3 represent the experimental groups to which the feed additive composition of Examples 1-3 is added. DETAILED DESCRIPTION

[0038] To make the objectives, technical solutions, and advantages of the present invention more clear, the technical solutions of the present invention are described clearly and completely below. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0039] Example 1

[0040] This embodiment provides a feed additive composition, which is composed of the following components in parts by weight: 30 parts of ursolic acid, 5 parts of raffinose, 15 parts of isochlorogenic acid C, and 15 parts of α-solanol.

[0041] Example 2

[0042] This embodiment provides a feed additive composition, which is composed of the following components in parts by weight: 45 parts of ursolic acid, 10 parts of raffinose, 10 parts of isochlorogenic acid C, and 5 parts of α-solanol.

[0043] Example 3

[0044] This embodiment provides a feed additive composition, which is composed of the following components in parts by weight: 60 parts of ursolic acid, 5 parts of raffinose, 5 parts of isochlorogenic acid C, and 10 parts of α-solanol.

[0045] Comparative Example 1

[0046] This comparative example provides a feed additive composition, which is composed of the following components in parts by weight: 30 parts of ursolic acid, 5 parts of galacto-oligosaccharide, 15 parts of isochlorogenic acid C, and 15 parts of α-solanol.

[0047] Comparative Example 2

[0048] This comparative example provides a feed additive consisting only of ursolic acid.

[0049] Comparative Example 3

[0050] This comparative example provides a feed additive consisting only of raffinose.

[0051] Comparative Example 4

[0052] This comparative example provides a feed additive consisting only of isochlorogenic acid C.

[0053] Comparative Example 5

[0054] This comparative example provides a feed additive consisting only of α-solanol.

[0055] Experimental example

[0056] 1. Experimental Design

[0057] 1,296 healthy, one-day-old AA male broiler chickens of similar weight were randomly divided into nine groups, with six replicates per group and 24 chickens per replicate. The control group was fed a corn-soybean meal basal diet, which was a powdered compound feed formulated according to the NRC (1994). Its composition and nutritional levels are shown in Table 1. The experimental groups were fed a basal diet supplemented with the feed additive compositions or feed additives of each Example and Comparative Example. The feed additive compositions of Examples 1-3 were added at a rate of 250 mg / kg of basal diet, and the feed additive compositions or feed additives of Comparative Examples 1-5 were also added at a rate of 250 mg / kg of basal diet. The experimental period was 42 days.

[0058] Table 1 Basic diet composition and nutrient levels (air-dried basis)

[0059]

[0060]

[0061] Note: 1) Premix provides the following per kg of feed: Vitamin A 12,500 IU, Vitamin D3 2,600 IU, Vitamin E 50 IU, Vitamin K3 4 mg, Riboflavin 5.00 mg, D-calcium pantothenate 24 mg, Niacin 55 mg, Vitamin B12 0.03 mg, Manganese (MnSO4·H2O) 55 mg, Iron (FeSO4·H2O) 75 mg, Zinc (ZnSO4·7H2O) 36 mg, Copper (CuSO4·5H2O) 8 mg, and Selenium (Na2SeO3) 0.15 mg. 2) Nutrient levels are calculated values.

[0062] 2. Feeding and management

[0063] The experimental broilers were housed in three-tiered cages. The broiler houses and equipment were thoroughly rinsed and disinfected before the experiment. The broiler houses were temperature-controlled with electric intelligent heaters. Continuous lighting, natural ventilation, and longitudinal negative pressure ventilation were used. During the experimental period, lighting, relative humidity, and temperature were controlled according to AA broiler husbandry and management requirements. The broiler houses were cleaned regularly, and immunizations were performed according to normal procedures. Throughout the experimental period, the birds had free access to food and water. The temperature and humidity in the broiler houses were recorded daily at 08:00, 12:00, and 18:00. During the experimental period, the feed intake, water intake, and health status of the test birds were observed and recorded daily. Mortalities and feed consumption were also recorded.

[0064] 3. Measurement indicators and methods

[0065] 3.1 Intestinal morphology indicators

[0066] On the 43rd day of the experiment, one broiler chicken with a near-average body weight was randomly selected from each replicate for slaughter. The duodenum, jejunum, and ileum were separated, and about 1.5 cm of the middle intestinal segment was fixed in 4% paraformaldehyde solution. The fixed intestinal segment was dehydrated with ethanol, transparentized with xylene, embedded in paraffin, and sectioned. It was then stained with hematoxylin-eosin (HE) and observed under an optical microscope. The villus height (VH) and crypt depth (CD) of the intestinal segment were measured, and the ratio of villus height to crypt depth (villus-crypt ratio, VH / CD) was calculated.

[0067] 3.2 Cecal microbial assay

[0068] The cecal contents of the above-slaughtered broilers were collected under sterile conditions and sent to Biomike Biotechnology Co., Ltd. Based on the PacBio sequencing platform, the single-molecule real-time sequencing (SMRT Cell) method was used to sequence the cecal content bacterial genome and perform bioinformatics analysis.

[0069] 4. Data statistical analysis

[0070] All experimental data were analyzed by one-way analysis of variance using SPSS 20 software.

[0071] 5. Test results

[0072] 5.1 Intestinal morphology indicators

[0073] The results are shown in Table 2. It can be seen from Table 2 that, compared with the control group and each comparative example, the feed additive composition of the embodiment can significantly increase the villus crypt ratio of the duodenum, jejunum and ileum (p < 0.05); compared with the control group, each embodiment significantly increased the villus height of the duodenum, jejunum and ileum, and significantly reduced the crypt depth of the duodenum and jejunum (p < 0.05). In addition, the feed additive composition of each embodiment has a better regulating effect on the villus crypt ratio, villus height and crypt depth than each comparative example, indicating that the feed additive composition of the present invention can significantly improve intestinal morphology and promote intestinal health. Under the condition of the same dietary addition amount, the feed additive composition of each embodiment has a synergistic effect in improving the villus crypt ratio of the duodenum, jejunum and ileum, improving the villus height of the ileum and reducing the crypt depth of the duodenum than comparative examples 2-5 of each component of the composition added alone, indicating that ursolic acid, raffinose, isochlorogenic acid C and α-chlorogenic acid in the feed additive composition of the present invention have a synergistic effect in improving intestinal morphology, promoting intestinal absorption and health.

[0074] Table 2 Effects of adding different compositions to the diet on the intestinal morphology of broiler chickens

[0075]

[0076]

[0077] Note: In the same row of data, data marked with the same letter or no letter indicate no significant difference (P≥0.05), and data marked with different letters indicate significant difference (P<0.05).

[0078] 5.2 Cecal microbial indicators

[0079] The results are as follows Figure 1 As shown in Table 3, at the phylum level, the relative abundance of Firmicutes, Bacteroidota, and Proteobacteria reached more than 90%. Combined with the relative abundance results in Table 3, it can be seen that in terms of the composition of cecal microorganisms at the phylum level, adding the feed additive composition of each embodiment to the feed can significantly increase the relative abundance of Firmicutes, while significantly reducing the relative abundance of Bacteroidetes (P<0.05). Adding the composition of each embodiment can increase the ratio of Firmicutes to Bacteroidetes in the cecum of broiler chickens, thereby improving the nutrient utilization efficiency of broilers and promoting the growth and development of broilers. In addition, adding the composition of each embodiment can also significantly reduce the relative abundance of Proteobacteria in the cecum of broiler chickens (P<0.05).

[0080] Table 3 Effects of the composition on the relative abundance of dominant phyla of cecal microorganisms in broiler chickens

[0081]

[0082] Research shows that the lifting of Firmicutes relative abundance in intestinal tract is conducive to body absorption of the heat in food, can also promote the decomposition of microbial flora to cellulose, and the short-chain fatty acid of its production is conducive to maintaining body intestinal health. In addition, research shows that the Bacteroidetes relative abundance in its intestinal tract of mice with relatively thin body size is relatively high, and more (Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI.An obesity-associated gut microbiome with increased capacity for energy harvest.Nature.2006Dec 21 than fat mice intestinal tract enrichment Firmicutes; 444 (7122): 1027-31.). It can be seen from this that feed additive composition of the present invention can promote the raising of broiler growth performance by adjusting the ratio of Firmicutes and Bacteroidetes relative abundance in intestinal tract flora.

[0083] The above results show that the feed additive composition of the present invention can significantly improve the intestinal morphology of broiler chickens, regulate the intestinal microbial population, and increase the abundance of beneficial bacteria, thereby achieving the effects of protecting the intestinal health of livestock and poultry, promoting the growth of livestock and poultry, and improving immunity.

[0084] At the same time, the present invention also verifies the effect of the feed additive composition of each embodiment on laying hens with reference to the above method. The results show that the feed additive composition of the present invention can significantly improve the intestinal morphology of laying hens, increase the abundance of probiotics in the intestinal tract of laying hens, and reduce the abundance of harmful bacteria, thereby achieving the purpose of improving the intestinal health of laying hens.

[0085] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A feed additive composition, characterized in that The composition comprises the following components in parts by weight: 25-65 parts of ursolic acid, 1-10 parts of raffinose, 1-15 parts of isochlorogenic acid C, and 1-15 parts of α-solanol.

2. The feed additive composition according to claim 1, characterized in that In the composition, the mass ratio of ursolic acid to α-solanol is (2-10):

1.

3. The feed additive composition according to claim 1, characterized in that In the composition, the mass ratio of raffinose to α-solanol is 1:(0.5-3).

4. The feed additive composition according to claim 1, characterized in that In the composition, the mass ratio of isochlorogenic acid C to α-chlorogenic acid is (0.5-2):

1.

5. The feed additive composition according to claim 1, characterized in that The feed additive composition comprises the following components in parts by weight: 30-60 parts of ursolic acid, 5-10 parts of raffinose, 5-15 parts of isochlorogenic acid C, and 5-15 parts of α-solanol.

6. Use of the feed additive composition according to any one of claims 1 to 5 in feed additive or feed preparation.

7. A feed, characterized in that The feed comprises the feed additive composition according to any one of claims 1 to 5.

8. The feed according to claim 7, characterized in that In the feed, the mass percentage of the feed additive composition is 0.01-0.1%.

9. Use of the feed additive composition according to any one of claims 1 to 5 or the feed according to claim 7 or 8 in improving the intestinal morphology and / or improving the intestinal microbial composition of livestock and poultry.

10. The use according to claim 9, characterized in that The improving of the intestinal morphology of livestock and poultry includes increasing the height of the villi in the intestinal tract of livestock and poultry, decreasing the depth of the crypts in the intestinal tract of livestock and poultry and / or increasing the ratio of the height of the villi to the depth of the crypts in the intestinal tract of livestock and poultry.

11. The use according to claim 9, characterized in that The improving of the intestinal microbial composition of livestock and poultry includes increasing the abundance of Firmicutes, decreasing the abundance of Bacteroidetes, increasing the abundance ratio of Firmicutes to Bacteroidetes, and / or decreasing the abundance of Proteobacteria.

12. The use according to any one of claims 9 to 11, characterized in that: The application comprises: administering the feed additive composition or the feed to livestock and poultry, wherein the administration amount of the feed additive composition is 250-750 mg per kilogram of basic diet.

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