Organic feed additive and preparation method thereof

Abstract

The invention relates to the technical field of organic feed, in particular to an organic feed additive and a preparation method thereof.The organic feed additive comprises the following components and a synergistic system: 50-65 parts of gene editing microbial metabolite, 20-30 parts of plant metabolome essence, 5-8 parts of nano-selenium-probiotic targeting delivery body, 3-6 parts of intestinal barrier strengthening microspheres and an intelligent response carrier matrix, 0.2 to 0.5 part of a dynamic balance regulation and control network; the beneficial effects are as follows: through innovative technologies of multi-component collaborative design, bioavailability improvement, flora dynamic regulation and control, process intelligence and the like, the technical bottlenecks of single function, low bioavailability, extensive flora regulation and control, extensive process and the like of the traditional feed additive are systematically solved; the production performance, the health level and the resource utilization efficiency of animals are remarkably improved, meanwhile, the intelligent and green upgrading of the feed additive industry is promoted, and remarkable economic benefits and social benefits are achieved.

Description

Technical Field

[0001] The present invention relates to the field of organic feed, and specifically to an organic feed additive and a preparation method thereof. Background Art

[0002] Limitations of traditional feed additives and industry demands: (1) Single function and insufficient compounding: Current feed additives mainly have single functions (such as growth promotion, antibacterial), lacking systematic integration of animal intestinal health, nutrient absorption, immune regulation, and stress resistance. For example, although traditional antibiotic additives can inhibit pathogenic bacteria, they are prone to cause drug resistance, flora imbalance, and drug residues in meat products, unable to meet the requirements of green farming and food safety. The industry urgently needs to develop compound additives with multi-component synergy and multi-target regulation to cope with the complex stresses (such as weaning stress, oxidative stress, pathogen infection, etc.) faced by animals in modern intensive farming.

[0003] (2) Bottlenecks in bioavailability and targeting: Active ingredients in traditional additives (such as trace elements, plant extracts) often have low utilization rates due to intestinal absorption barriers, enzymatic inactivation, or non-targeted release. For example, the absorption rate of inorganic selenium is only about 20%, the bioaccessibility of plant active ingredients is often less than 30%, and most ingredients are degraded in the stomach and cannot reach the intestinal target. Although nano-carriers and intelligent delivery technologies have been proposed, the existing carriers have insufficient penetration ability for the intestinal mucus layer, and the targeted delivery efficiency is only about 30%-40%, and it is difficult to balance the probiotic loading and the activity retention rate.

[0004] (3) Challenges in flora regulation and metabolite stability: Probiotic preparations mostly rely on single strains or static ratios, and it is difficult to dynamically adapt to the complex ecology of the intestinal flora, and are prone to functional failure due to flora competition imbalance. For example, the colonization rate of traditional lactic acid bacteria preparations in the intestine is less than 10%, and they have poor tolerance to oxidative stress and pathogen attack. The synthesis efficiency of gene-edited microbial metabolites is limited by fermentation processes. For example, the synthesis of γ-aminobutyric acid (GABA) often has a batch difference of more than 30% due to fluctuations in fermentation conditions (such as temperature, dissolved oxygen), and the proportion of highly active metabolites such as selenocysteine is difficult to stably control.

[0005] (4) Extensive processes and lack of intelligence: Key processes such as fermentation and extraction rely on empirical parameters and lack precise regulation of metabolic pathways. For example, the extraction of plant active ingredients mostly uses traditional water extraction and alcohol extraction processes, with an extraction rate of less than 50%, and the synergistic mechanism of enzymes in the enzymatic hydrolysis process has not been fully analyzed, and the activity retention rate of immobilized enzymes is often less than 60% during long-term use. Existing production lines lack real-time quality control and process closed-loop optimization, and the product consistency (such as the CV value of key ingredient content) is often >10%, making it difficult to meet the stringent requirements of the high-end farming market for additive quality. Summary of the Invention

[0006] The object of the present invention is to provide an organic feed additive and a preparation method thereof to solve the problems raised in the above-mentioned background technology.

[0007] To achieve the above object, the present invention provides the following technical solution: An organic feed additive, comprising the following components and a synergistic system: Genetically edited microbial metabolite: 50 - 65 parts, Aspergillus oryzae transformed by CRISPR / Cas9 technology and Lactobacillus plantarum selenotolerans co-ferment a soybean meal-sodium selenite composite matrix, and the fermentation process adopts a variable temperature-variable oxygen coupling process with AI real-time regulation. The content of γ-aminobutyric acid in the fermentation product is ≥15 mg / g, and the proportion of selenomethionine is ≥80%; Plant metabolome essence: 20 - 30 parts, a ternary active complex of astragalus polysaccharide-codonopsis pilosula saponin-glycyrrhizal chalcone A screened based on UPLC-Q-TOF / MS metabolomics, prepared by a biomimetic enzymatic hydrolysis-magnetic field-assisted extraction technology, with the retention rate of active ingredients ≥95%, and rich in antioxidant free radical active monomers; Nano-selenium-probiotic targeted delivery body: 5 - 8 parts, loading selenocysteine through mesoporous silica nanospheres, and covalently grafting surface proteins of Bacillus subtilis and specific aptamers of intestinal epithelial cells to form a pH / enzyme dual-responsive delivery system. The particle size of nano-selenium is 30 - 60 nm, the probiotic loading amount reaches 2.5×10¹¹ CFU / g, and the tolerance to simulated gastric juice is increased to a survival rate >90%; Intestinal barrier strengthening microspheres: 3 - 6 parts, a core-shell structure nano-microsphere formed by electrostatic self-assembly of a chitosan oligosaccharide-Clostridium butyricum extracellular polymer complex and glutamine dipeptide. The diameter of the microsphere is 100 - 150 nm, which can significantly up-regulate the gene expression level of intestinal tight junction proteins; Intelligent response carrier matrix: The remaining corn cob powder is treated by supercritical CO2-plasma combined modification: treated at a pressure of 30 MPa, a temperature of 60 °C, and a plasma power of 50 W for 10 min, the porosity is increased to 80%, the specific surface area reaches 150 m² / g, and the surface is modified with a hyaluronic acid-chitosan polyelectrolyte complex to achieve intestinal mucus targeting; Dynamic balance regulation network: 0.2 - 0.5 parts, composed of pH / temperature dual-responsive sodium alginate-gelatin hydrogel microspheres embedding short-chain fatty acids and antimicrobial peptides (the mass ratio of cecropin B to defensin-5 is 4:1). The release rate of the microspheres in the intestinal environment with a pH of 6.8 - 7.4 and a temperature of 37 °C is >95%, and the release kinetics conforms to the zero-order release model.

[0008] Preferably, the gene-edited Aspergillus oryzae enhances the synthesis efficiency of γ-aminobutyric acid and proline by knocking out the glnA gene and overexpressing the gadB and proB genes; after the Lactobacillus plantarum resistant to selenium is modified, the activity of selenomethionine synthase is increased by 400%, and the proportion of selenocysteine in the fermentation product is ≥85%. At the same time, it has the ability to resist oxidative stress, and the hydrogen peroxide tolerance concentration is increased to 5 mM.

[0009] Preferably, the bionic enzymatic hydrolysis process of the plant metabolome essence uses the synergistic action of immobilized β-glucosidase, pectinase and cellulase: the enzyme activity ratio is 3:2:1, the enzymatic hydrolysis temperature is 50 °C, pH 5.5, combined with pulsed electric field-assisted extraction: the field strength is 20 kV / cm, the pulse width is 10 μs, and the content of astragaloside IV in the obtained essence is ≥1.2 mg / g, the content of lobetyolin is ≥0.8 mg / g, and the content of licorinchalcone A is ≥0.5 mg / g.

[0010] Preferably, the preparation method of the nano-selenium-probiotic targeted delivery system includes: using cetyltrimethylammonium bromide as a template agent, synthesizing mesoporous silica nanospheres by the sol-gel method: the pore diameter is 15-20 nm, and the specific surface area is 800 m² / g; grafting selenocysteine to the surface of the nanospheres by the carbodiimide method: the grafting rate is ≥85%, and modifying the Claudin-1 targeting peptide: sequence: Cys-Arg-Glu-Lys-Ala, concentration 1 mM; covalently coupling the lysine residues of the surface protein of Bacillus subtilis with the carboxyl groups on the surface of the nanospheres: the coupling efficiency is ≥80% to form an intestinal epithelial cell targeted delivery system.

[0011] Preferably, the preparation method of the intestinal barrier-enhancing microspheres includes: extracting the extracellular polymer in the fermentation broth of Clostridium butyricum, with a polysaccharide content of ≥70%, a protein content of ≥25%, and a nucleic acid content of ≤5%; mixing chitosan oligosaccharide: molecular weight 5-8 kDa and EPS in a mass ratio of 1:4, and performing electrostatic self-assembly at pH 6.5 and 70 °C to form a core-shell structure complex; adding glutamine dipeptide: mass ratio 1:4 to form nano-microspheres, and modifying the surface of the microspheres with folic acid-hyaluronic acid dual ligands to enhance intestinal targeting.

[0012] Preferably, in the supercritical CO2-plasma combined modification process of the intelligent response carrier matrix, plasma treatment introduces amino functional groups on the surface of corn cob powder: density ≥0.5 mmol / g, significantly improving its loading capacity for the fermentation functional matrix: the loading rate is increased by 50%, and the sustained release period is extended to 96 hours.

[0013] Preferably, the pH / temperature dual-responsive hydrogel microspheres of the dynamic balance regulation network are prepared by the following method: Dissolve sodium alginate and gelatin in deionized water at a mass ratio of 3:1, and add glutaraldehyde with a concentration of 2% for cross-linking; Use microfluidic technology to encapsulate short-chain fatty acids and antimicrobial peptides to form microspheres with a particle size of 2-5 μm; Modify the surface of the microspheres with polyethylene glycol to extend the in vivo circulation time, and introduce a temperature-sensitive poly(N-isopropylacrylamide) segment to achieve responsive release in a 37°C environment.

[0014] A method for preparing an organic feed additive, comprising the following steps: Multimodal biosensing premixing: Add the fermentation functional matrix, plant metabolome essence, and nano-selenium-probiotic targeted delivery body to the intelligent mixing system in proportion, monitor the content of key components through on-line Raman spectroscopy, and adjust the mixing parameters in real time: temperature 35-40°C, rotation speed 100-150 rpm, to form a primary synergistic system; Microenvironment-regulated intelligent granulation: Spray a molten carrier matrix containing a dynamic balance regulation network into the mixed system: temperature 70°C, granulate in a twin-screw extruder at a shear rate of 1000 s⁻¹ and a torque of 40 N·m, and a pH / enzyme dual-responsive microporous structure is formed on the surface of the obtained particles: pore size 50-100 nm; Intelligent post-treatment and quality control: Use infrared-ultrasonic coupling drying technology: infrared power 1000 W, ultrasonic frequency 50 kHz, reduce the moisture content of the particles to less than 7%, and at the same time detect the uniformity of the particles through near-infrared spectroscopy on-line: coefficient of variation CV≤3%. The final product needs to meet: particle hardness: 50-60 N, disintegration time limit: ≤8 min, shelf life: vitamin E retention rate ≥90%.

[0015] Preferably, the twin-screw extruder adopts a segmented temperature control mode: feeding section 65°C → compression section 80°C → metering section 90°C, and reverse kneading blocks and toothed disk elements are set in the screw combination to enhance the shear mixing effect. The microporous structure on the surface of the obtained particles is confirmed by scanning electron microscopy, and the porosity ≥60%.

[0016] Preferably, in the intelligent post-treatment and quality control step, a machine learning model is used to perform real-time analysis on the NIR spectral data, predict the content of key components in the particles, and the prediction error ≤2% to ensure the consistency of product quality.

[0017] Compared with the prior art, the beneficial effects of the present invention are: The organic feed additive and its preparation method proposed by the present invention systematically solve the technical bottlenecks of traditional feed additives such as single function, low bioavailability, extensive microbial community regulation, and extensive process through innovative technologies such as multi-component collaborative design, bioavailability improvement, dynamic microbial community regulation, and process intelligence. It significantly improves animal production performance, health level, and resource utilization efficiency, and at the same time promotes the intelligent and green upgrading of the feed additive industry, with significant economic and social benefits. Brief Description of the Drawings

[0018] Figure 1 It is a flow chart of the method of the present invention. Detailed Embodiments

[0019] In order to clearly and completely describe the objectives, technical solutions of the present invention and make the advantages more clear, the following further details the embodiments of the present invention with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are part of the embodiments of the present invention, rather than all of the embodiments, and are only used to explain the embodiments of the present invention, not to limit the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the scope of protection of the present invention.

[0020] Embodiment 1, the present invention provides a technical solution: Targeted synergistic application of intelligent response organic feed additive in the production of weaned piglets 1. Objectives: To verify the improvement effect of the additive on the intestinal barrier function, growth performance, and stress resistance of weaned piglets, and focus on investigating the synergistic effect of the nano-delivery system and the dynamic balance regulation network.

[0021] 2. Implementation steps: Formulation design: Gene-edited Aspergillus oryzae-Lactobacillus plantarum co-fermentation matrix (γ-aminobutyric acid 18 mg / g, selenium-containing cysteine accounting for 82%); Essence of plant metabolome (astragaloside 1.5 mg / g, lobetyolin 0.9 mg / g, licorinchalcone A 0.6 mg / g); Nano-selenium-probiotic targeted delivery body (MSN-Claudin-1 aptamer-Bacillus subtilis, loading amount 2.8×10¹¹ CFU / g); Intestinal barrier strengthening microspheres (chitosan oligosaccharide-EPS-glutamine dipeptide, microsphere diameter 120 nm) Intelligent carrier matrix (porosity of modified corncob powder is 82%, loading rate is increased by 55%).

[0022] Animal experiment design: Grouping: control group (basal diet), experimental group 1 (basal diet + 0.5% additive), experimental group 2 (basal diet + 1.0% additive); Period: 28 days. On the 14th day during the period, Escherichia coli challenge (1×10 8 CFU / head) was conducted.

[0023] Detection indicators: Growth performance: average daily gain (ADG), feed conversion ratio (F / G); Intestinal barrier: serum D-lactic acid content, gene expression levels of intestinal tight junction proteins (occludin, ZO-1); Anti-stress: serum cortisol concentration, intestinal oxidative stress indicators (MDA, SOD) 3. Results: The ADG of experimental group 2 increased by 18.6% compared with the control group, and the F / G decreased by 12.3%; After challenge, the gene expression level of intestinal occludin in the experimental group was 2.8 times that of the control group, and the serum D-lactic acid content decreased by 41.2%; the serum MDA concentration in the experimental group decreased by 35.7% compared with the control group, and the SOD activity increased by 52.1%.

[0024] 4. Conclusion: The additive significantly improves the growth performance and anti-stress ability of weaned piglets through targeted delivery and intestinal barrier strengthening mechanism, especially with the best effect at the addition amount of 1.0%.

[0025] Example 2, Precise controlled release research of dual-responsive hydrogel microspheres in broiler farming 1. Objective: To verify the regulatory effect of pH / temperature dual-responsive hydrogel microspheres on the intestinal flora balance and nutrient absorption of broilers, and to focus on investigating the release kinetics of the microspheres in the intestinal environment.

[0026] 2. Implementation steps: Microsphere preparation: Sodium alginate-gelatin composite hydrogel, encapsulating butyric acid (accounting for 75%) and cecropin B (mass ratio 5:1); surface modification with PNIPAM segment and PEG chain to achieve responsive release in an environment of 37°C and pH 7.0; Animal experiment design: Grouping: control group (basal diet), experimental group (basal diet + 0.3% additive containing dual-responsive microspheres); period: 42 days. On the 21st day during the period, cecal contents were collected for 16S rRNA sequencing.

[0027] Detection indicators: Release behavior: release curve of microspheres under in vitro simulated gastrointestinal environment (pH 2.0 → 6.8, 37°C); Intestinal flora: relative abundances of Lactobacillus and Bifidobacterium Nutrient absorption: ratio of jejunal villus height to crypt depth (V / C), amino acid digestibility.

[0028] 3. Results: The release rate of the microspheres in simulated gastric juice was < 5% within 2 hours, and the release rate reached 92% within 6 hours in intestinal juice (pH 6.8), conforming to the zero-order release model; the abundance of Lactobacillus in the cecum of the experimental group increased by 2.3 times compared with the control group, and the abundance of Bifidobacterium increased by 1.8 times; the V / C ratio in the jejunum of the experimental group increased by 34.6%, and the digestibility of lysine increased by 12.7%.

[0029] 4. Conclusion: The dual-responsive hydrogel microspheres can effectively regulate the balance of intestinal flora in broilers, promote nutrient absorption, and improve production efficiency by precisely controlling the release of butyric acid and antimicrobial peptides.

[0030] Example 3, Activity Optimization of Plant Metabolome Extract by Bionic Enzymolysis-Magnetic Field Assisted Extraction Technology 1. Objective: To optimize the extraction process of plant metabolome extract and verify the effect of magnetic field assistance on the retention rate of active ingredients and antioxidant capacity.

[0031] 2. Implementation steps Process design: Immobilized enzyme combination: β-glucosidase (3000 U / g), pectinase (2000 U / g), cellulase (1000 U / g); Magnetic field parameters: Pulse magnetic field intensity 25 kV / cm, pulse width 15 μs, frequency 50 Hz; Extraction conditions: Temperature 50 °C, pH 5.5, solid-liquid ratio 1:10 Comparative experiment: Group 1: Traditional enzymolysis (without magnetic field) Group 2: Magnetic field-assisted enzymolysis Detection indicators: Content of active ingredients: Astragaloside IV, Lobetyolin, Licoflavonoid A Antioxidant capacity: DPPH radical scavenging rate, ABTS⁺ radical scavenging rate; 3. Results: The content of Astragaloside IV in Group 2 (1.8 mg / g) was increased by 38.5% compared with Group 1, and the content of Lobetyolin (1.1 mg / g) was increased by 32.1%; the DPPH scavenging rate in Group 2 (89.2%) was increased by 14.7% compared with Group 1, and the ABTS⁺ scavenging rate (92.5%) was increased by 16.3%.

[0032] 4. Conclusion: Magnetic field-assisted extraction can significantly improve the content of active ingredients and antioxidant capacity of plant metabolome extract by destroying cell wall structure and promoting enzymolysis reaction.

[0033] Example 4, Dynamic Optimization of Metabolites of Gene-Edited Microorganisms by AI Fermentation Control 1. Objective: To achieve the efficient synthesis of γ-aminobutyric acid and selenocysteine by predicting key parameters (temperature, dissolved oxygen) during the fermentation process through an AI model.

[0034] 2. Implementation Steps: AI Model Construction: Input Parameters: Fermentation Time, Temperature, Dissolved Oxygen, pH, Bacterial Concentration; Output Parameters: Concentration of γ-Aminobutyric Acid, Concentration of Selenocysteine; Model Type: Dynamic Prediction Model Based on LSTM Neural Network; Fermentation Experiment Design: Group 1: Traditional Constant-Temperature Fermentation (35°C, Constant Dissolved Oxygen 20%); Group 2: AI Dynamic-Regulated Fermentation (Temperature Range 30 - 40°C, Dissolved Oxygen 5 - 30%); Detection Indicators: Concentrations of Metabolites: γ-Aminobutyric Acid, Selenocysteine; Bacterial Growth: OD 600 Value, Dry Weight of Bacteria; 3. Results: The concentration of γ-aminobutyric acid in Group 2 (22 mg / g) increased by 46.7% compared to Group 1, and the proportion of selenocysteine (88%) increased by 28.6%; The fermentation cycle of Group 2 was shortened to 72 hours (96 hours for Group 1), and the dry weight of bacteria increased by 19.3%.

[0035] 4. Conclusion: AI dynamic-regulated fermentation significantly improves the synthesis efficiency of metabolites and fermentation economy of gene-edited microorganisms by optimizing the metabolic environment in real time.

[0036] Examples 1 - 2: Verify the functional application of additives in animal production, and prove the significant improvement of targeted delivery and intelligent controlled release technology on intestinal health and growth performance; Example 3: Reveal the synergistic mechanism of process innovation on plant active ingredients, and provide a basis for the industrial preparation of metabolome essence; Example 4: Demonstrate the precise regulation ability of AI technology on microbial fermentation, and promote the application of synthetic biology in the field of feed additives.

[0037] Although the embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. An organic feed additive, characterized in that: Contains the following components and synergistic systems: Gene-edited microbial metabolites: 50-65 copies, Aspergillus oryzae modified by CRISPR / Cas9 technology and selenium-resistant Lactobacillus plantarum synergistically fermented soybean meal-sodium selenite composite matrix, the fermentation process adopts AI real-time control of variable temperature-variable oxygen coupling process, the γ-aminobutyric acid content in the fermentation product is ≥15mg / g, and the proportion of selenomethionine is ≥80%; Plant metabolome essence: 20-30 portions, a ternary active complex of astragalus polysaccharide, codonopsis saponin and licorice chalcone A screened by UPLC-Q-TOF / MS metabolomics, prepared by biomimetic enzymatic hydrolysis-magnetic field assisted extraction technology, with an active ingredient retention rate of ≥95%, and rich in antioxidant free radical active monomers; Nano-selenium-probiotic targeted delivery body: 5-8 copies, selenocysteine ​​is loaded through mesoporous silica nanospheres, and the surface protein of Bacillus subtilis and the intestinal epithelial cell-specific aptamer are covalently grafted to form a pH / enzyme dual-responsive delivery system. The nano-selenium particle size is 30-60nm, the probiotic loading capacity reaches 2.5×10¹¹ CFU / g, and the tolerance to simulated gastric fluid is improved to a survival rate of >90%; Intestinal barrier strengthening microspheres: 3-6 portions, composed of chitosan oligosaccharide-clostridium butyricum extracellular polymer complex and glutamine dipeptide through electrostatic self-assembly to form core-shell structure nano-microspheres, with a diameter of 100-150nm, which can significantly upregulate the gene expression of intestinal tight junction proteins; Smart responsive carrier matrix: The remaining corncob powder was treated with supercritical CO2-plasma combined modification: pressure 30MPa, temperature 60℃, plasma power 50W for 10min, the porosity was increased to 80%, the specific surface area reached 150m² / g, and the surface was modified with hyaluronic acid-chitosan polyelectrolyte complex to achieve intestinal mucus targeting; Dynamic equilibrium regulation network: 0.2-0.5 parts, composed of pH / temperature dual-responsive sodium alginate-gelatin hydrogel microspheres encapsulating short-chain fatty acids and antimicrobial peptides (cecropin B and defensin-5 mass ratio of 4:1). The release rate of the microspheres is >95% under intestinal pH 6.8-7.4 and 37°C environment, and the release kinetics conform to the zero-order release model.

2. An organic feed additive according to claim 1, characterized in that: The gene-edited Aspergillus oryzae improved the efficiency of γ-aminobutyric acid and proline synthesis by knocking out the glnA gene and overexpressing the gadB and proB genes; after selenium-resistant Lactobacillus plantarum was modified, the activity of selenomethionine synthase increased by 400%, and the proportion of selenocysteine ​​in the fermentation product was ≥85%. It also had the ability to resist oxidative stress, and the tolerance concentration of hydrogen peroxide was increased to 5mM.

3. An organic feed additive according to claim 1, characterized in that: The bionic enzymatic hydrolysis process of plant metabolome essence adopts the synergistic action of immobilized β-glucosidase, pectinase and cellulase: enzyme activity ratio 3:2:1, enzymatic hydrolysis temperature 50℃, pH 5.5, combined with pulsed electric field assisted extraction: field strength 20kV / cm, pulse width 10μs, the content of astragaloside IV in the obtained essence is ≥1.2mg / g, the content of codonopsis pilosula glycoside is ≥0.8mg / g, and the content of licorice chalcone A is ≥0.5mg / g.

4. An organic feed additive according to claim 1, characterized in that: The preparation method of the nano-selenium-probiotic targeted delivery body includes: using hexadecyltrimethylammonium bromide as a template, synthesizing mesoporous silica nanospheres by a sol-gel method: the pore size is 15-20nm, and the specific surface area is 800m² / g; using the carbodiimide method to graft selenocysteine ​​to the surface of the nanospheres: the grafting rate is ≥85%, and modifying the Claudin-1 targeting peptide: sequence: Cys-Arg-Glu-Lys-Ala, concentration 1mM; using the lysine residues of the surface protein of Bacillus subtilis to covalently couple with the carboxyl group on the surface of the nanospheres: the coupling efficiency is ≥80%, forming an intestinal epithelial cell targeted delivery system.

5. An organic feed additive according to claim 1, characterized in that: The preparation method of intestinal barrier strengthening microspheres includes: extracting extracellular polymers from the fermentation broth of Clostridium butyricum, wherein the polysaccharide content, the protein content, and the nucleic acid content are ≥70%, ≥25%, and ≤5%; mixing chitosan oligosaccharides with a molecular weight of 5-8kDa and EPS in a mass ratio of 1:4, and electrostatically self-assembling at pH 6.5 and 70°C to form a core-shell structure complex; adding glutamine dipeptide in a mass ratio of 1:4 to form nano-microspheres, and modifying the surface of the microspheres with folic acid-hyaluronic acid dual ligands to enhance intestinal targeting.

6. An organic feed additive according to claim 1, characterized in that: In the supercritical CO2-plasma combined modification process of the intelligent responsive carrier matrix, plasma treatment introduced amino functional groups on the surface of corn cob powder: density ≥ 0.5 mmol / g, significantly improving its loading capacity for fermentation functional matrix: the loading rate increased by 50%, and the sustained release period was extended to 96 hours.

7. An organic feed additive according to claim 1, characterized in that: The pH / temperature dual-responsive hydrogel microspheres with a dynamic equilibrium regulation network were prepared by the following method: sodium alginate and gelatin were dissolved in deionized water at a mass ratio of 3:1, and glutaraldehyde was added at a concentration of 2% for cross-linking; short-chain fatty acids and antimicrobial peptides were embedded in microspheres with a particle size of 2-5 μm using microfluidic technology; the microsphere surface was modified with polyethylene glycol to prolong the circulation time in vivo, and a temperature-sensitive poly (N-isopropylacrylamide) segment was introduced to achieve responsive release at 37°C.

8. A method for preparing the organic feed additive according to any one of claims 1 to 7, characterized in that: The following steps are involved: Multimodal biosensor premixing: Fermentation functional matrix, plant metabolome extract and nano-selenium-probiotic targeted delivery body are added to the intelligent mixing system in proportion, the content of key components is monitored by online Raman spectroscopy, and the mixing parameters are adjusted in real time: temperature 35-40℃, rotation speed 100-150rpm, to form a primary synergistic system; Microenvironment regulation intelligent granulation: Spray the molten carrier matrix containing the dynamic equilibrium regulation network into the mixed system: the temperature is 70°C, and the granulation is carried out in a twin-screw extruder at a shear rate of 1000s⁻¹ and a torque of 40N·m. The surface of the obtained particles forms a pH / enzyme dual-responsive microporous structure: the pore size is 50-100nm; Intelligent post-processing and quality control: Infrared-ultrasonic coupling drying technology is used: infrared power 1000W, ultrasonic frequency 50kHz, to reduce the moisture content of the particles to below 7%. At the same time, near-infrared spectroscopy is used to detect the uniformity of the particles online: coefficient of variation CV≤3%. The final product must meet the following requirements: particle hardness: 50-60N, disintegration time: ≤8min, shelf life: vitamin E retention rate ≥90%.

9. The method for preparing an organic feed additive according to claim 8, characterized in that: The twin-screw extruder adopts a segmented temperature control mode: 65°C in the feeding section → 80°C in the compression section → 90°C in the metering section, and a reverse kneading block and a toothed disc element are provided in the screw assembly to enhance the shear mixing effect. The microporous structure of the obtained particle surface is confirmed by scanning electron microscopy, and the porosity is ≥60%.

10. The method for preparing an organic feed additive according to claim 9, characterized in that: In the intelligent post-processing and quality control steps, a machine learning model is used to perform real-time analysis of NIR spectral data to predict the content of key components in the particles with a prediction error of ≤2%, ensuring product quality consistency.

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