Colon-targeted micro-ecological regulation composition and application thereof in metabolism management

Abstract

The invention relates to a colon-targeted micro-ecological regulation composition. The colon-targeted micro-ecological regulation composition is prepared by compounding the following functional components in percentage by weight: 5-95% of a component A, 1-15% of a component B and 4-94% of a component C, the component A is resistant starch, the polymerization degree DP is greater than or equal to 15, and the crystallinity is greater than or equal to 35%; the component B is probiotics and is embedded through a complex coacervation method or an extrusion-gel method, the embedding rate is larger than or equal to 75%, and the particle size is 200-800 microns; the survival rate is greater than or equal to 60% after treatment in simulated gastric juice for 2 hours, and the survival rate is greater than or equal to 50% after treatment in simulated intestinal juice for 4 hours; the component C comprises functional nutritional auxiliary materials, the functional nutritional auxiliary materials comprise prebiotics and a medicinal and edible composition, and the prebiotics comprise rapid fermentation type prebiotics, medium-speed fermentation type prebiotics, slow fermentation type prebiotics and a non-fermentation type water-holding expansion component. By constructing a carbon source slow release-flora orientation-metabolism regulation ternary interaction collaborative network, accurate regulation and multi-target metabolism intervention of the whole digestive tract are realized.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of functional food technology, in particular to a composition for intervening in metabolic syndrome through a colon-targeted microecological regulation mechanism, and application thereof in preparing functional food with the efficacy of improving insulin resistance, optimizing intestinal flora structure and regulating energy metabolism. BACKGROUND

[0002] Metabolic syndrome is a complex metabolic disorder syndrome with central obesity, insulin resistance, glucose and lipid metabolism disorder and chronic low-grade inflammation as core pathological characteristics. The existing metabolic syndrome intervention products and strategies have many technical bottlenecks, which are embodied in the following aspects: (1) Defects in energy supply mode: Traditional meal replacement products mostly use rapidly digestible carbohydrates, which leads to postprandial blood glucose fluctuation amplitude > 3.5-4.0 mmol / L, and aggravates the process of insulin resistance; lack of time and space specificity of energy supply design in upper and lower digestive tract, which is a common defect of current weight management products.

[0003] (2) Insufficient application efficiency of probiotics: The survival rate of commercially available probiotic products after passing through the gastrointestinal tract is only 30-60%, and they lack the exclusive fermentation substrate required for colon-targeted colonization; some products have inconsistent live bacteria count with the label, and the effect of microbial regulation is difficult to last.

[0004] (3) Limited system regulation dimension: Single intervention means can only target a single pathological link of metabolic syndrome, and cannot simultaneously achieve multi-target regulation of "energy balance-barrier repair-inflammation inhibition", while the complexity of metabolic syndrome requires intervention strategies to cover at least 3 or more pathological links.

[0005] (4) Contradiction between safety and compliance: High-dose dietary fiber (> 15-20g / time) is easy to cause abdominal distension, flatulence and other gastrointestinal adverse reactions, leading to termination of intervention by users within 4-8 weeks; direct addition of ingredients with medicinal and edible properties may have poor taste and low bioavailability, further reducing compliance.

[0006] Therefore, there is an urgent need in the art for an innovative technical solution with multiple synergistic mechanisms to achieve precise regulation of the entire digestive tract, multi-target system intervention, high bioavailability and safety tolerance balance, in order to solve the technical problems of existing products. SUMMARY

[0007] (I) Technical problems to be solved The purpose of this invention is to overcome the shortcomings of the prior art and provide a colon-targeted microecological regulation composition for achieving sustained release in the upper digestive tract and fermentation-like function in the lower digestive tract, improving the colon-directed colonization rate of probiotics, regulating the activity of key enzymes in glucose and lipid metabolism, improving insulin resistance, inhibiting chronic low-grade inflammation, and simultaneously achieving multi-target regulation such as energy balance, intestinal barrier repair, and immune regulation. At the same time, sensory experience optimization technology is used to improve the product's taste and enhance long-term user compliance.

[0008] (II) Technical Solution The technical solution of the present invention is as follows: A colon-targeted microecological regulation composition, the active ingredients of which are compounded by weight percentage of component A (5-95%), component B (1-15%), and component C (4-94%). Component A is resistant starch with a degree of polymerization (DP) ≥ 15 and a crystallinity ≥ 35%. Component B is a probiotic, encapsulated using coagulation or extrusion-gel methods with an encapsulation rate ≥75%; its tolerance to overdigestion is satisfied: survival rate ≥60% after treatment in simulated gastric juice for 2 hours, and survival rate ≥50% after treatment in simulated intestinal juice for 4 hours. Component C contains functional nutritional excipients; functional nutritional excipients include prebiotics and food-medicine homologous compositions; prebiotics include fast-fermenting prebiotics, medium-fermenting prebiotics, slow-fermenting prebiotics, and non-fermenting water-holding and swelling components.

[0009] According to a preferred embodiment of the present invention, the fast-fermenting prebiotic is at least one selected from xylooligosaccharides, fructooligosaccharides, galactooligosaccharides, stachyose, and cottonseed oligosaccharides; the medium-fermenting prebiotic is at least one selected from inulin, oat β-glucan, pectin, and gum arabic; the slow-fermenting prebiotic is at least one selected from resistant dextrin, polydextrose, psyllium husk, and cellulose; and the non-fermenting water-holding swelling component is at least one selected from konjac flour, carrageenan, xanthan gum, and guar gum.

[0010] Preferably, the mass ratio of fast-fermenting, medium-fermenting, and slow-fermenting prebiotics to non-fermenting water-holding and swelling components in component C is (1.0-3.5):(1.0-4.5):(1.0-3.0):(1.0-2.0); the core optimal ratio is 2.0:2.0:2.0:1.0.

[0011] According to a preferred embodiment of the present invention, the food-medicine homology composition comprises one or more of the following: spleen-strengthening and dampness-eliminating food-medicine homology substances, heat-clearing and dampness-resolving food-medicine homology substances, digestion-aiding and food-medicine homology substances, bowel-moistening and laxative food-medicine homology substances, phlegm-resolving and dampness-eliminating food-medicine homology substances, qi-tonifying and yin-nourishing food-medicine homology substances, and other food-medicine homology substances. The spleen-strengthening and dampness-eliminating medicinal and edible substances are selected from at least one of Poria cocos, Coix seed, Dioscorea opposita, white hyacinth bean, and red adzuki bean; the heat-clearing and dampness-resolving medicinal and edible substances are selected from at least one of lotus leaf, cassia seed, chrysanthemum, honeysuckle, and gardenia; the digestive and food-resolving medicinal and edible substances are selected from at least one of hawthorn, radish seed, malt, and chicken gizzard lining; the bowel-moistening and laxative medicinal and edible substances are selected from at least one of hemp seed, Prunus japonica seed, mulberry, and black sesame; the phlegm-resolving and dampness-eliminating medicinal and edible substances are selected from at least one of tangerine peel, citron, perilla, ginger, and cinnamon; the qi-tonifying and yin-nourishing medicinal and edible substances are selected from at least one of Polygonatum sibiricum, Polygonatum odoratum, wolfberry, lily, and sea buckthorn; and other medicinal and edible substances are selected from at least one of Sophora japonica flower, dandelion, and agastache rugosa.

[0012] According to a preferred embodiment of the present invention, the formulation excipients are further included, the formulation excipients comprising a binder, a lubricant, and a disintegrant; the binder is at least one selected from sorbitol, maltodextrin, microcrystalline cellulose, lactose, compressible starch, polyethylene oxide, and povidone; the lubricant is at least one selected from magnesium stearate, stearic acid, calcium stearate, and silicon dioxide; and the disintegrant is at least one selected from sodium carboxymethyl starch and dry starch.

[0013] According to a preferred embodiment of the present invention, the food-medicine homologous substances in component C are subjected to one or more of the following processes to improve bioavailability: ultrafine pulverization and cell wall disruption, low-temperature extraction, supercritical CO2 extraction, and microwave-assisted extraction; the prebiotics are subjected to one or more of the following processes to modify them: microencapsulation, molecular weight classification, oxidative cross-linking, and mineral chelation.

[0014] According to a preferred embodiment of the present invention, the resistant starch of component A is a polysaccharide and its derivatives composed of D-glucose units linked by α-1,4 and / or α-1,6 glycosidic bonds, and its resistance is enhanced by wet heat modification treatment; the digestibility of component A is ≤30% based on the small intestinal digestibility determined by the ISO 26642:2010 method; and component B is one or a combination of two or more strains of Bifidobacterium, Lactobacillus, and Clostridium butyricum.

[0015] Secondly, the present invention provides the application of the above-mentioned colon-targeted microecological regulation composition in the preparation of functional foods for the intervention of metabolic syndrome.

[0016] Preferably, the functional food has one or more of the following effects: improving insulin resistance, optimizing intestinal flora structure, increasing the production of short-chain fatty acids in the intestine, regulating glucose and lipid metabolism, reducing body fat percentage, reducing waist circumference, repairing the intestinal mucosal barrier, and prolonging satiety time.

[0017] Preferably, for individuals with hyperglycemia, the effective components of the colon-targeted microecological regulation composition include component A (80-95%), component B (1-10%), and component C (4-10%); for individuals with comprehensive metabolic disorders, the effective components of the colon-targeted microecological regulation composition include component A (54-60%), component B (6-15%), and component C (22-35%).

[0018] Preferably, the functional food dosage form is powder or tablet; the powder specification is 3-25g / strip, and the tablet specification is 0.5-1.0g / tablet; the method of consumption is to take orally with warm water 30 minutes before breakfast and dinner, twice a day, each time 10g of powder or 1-2 tablets.

[0019] (III) Beneficial Effects Compared to the technical effects of existing technologies The colon-targeted microecological regulation composition and its application of the present invention, through the construction of a three-element core system of "slow-release carbon source-active probiotics-gradient prebiotics", combined with multi-component synergy and precise process design, solves many technical pain points of existing metabolic syndrome intervention products, and achieves the following significant technical effects compared with the prior art: 1. Achieve spatiotemporally specific energy supply, significantly reducing postprandial blood glucose fluctuations. After being modified by wet heat, the resistant starch in the composition resists hydrolysis in the upper digestive tract, reducing postprandial blood glucose response by 30-50% and avoiding the aggravation of insulin resistance caused by rapid carbohydrate digestion. In the colon, it is fermented as a substrate for probiotics to produce butyric acid, achieving precise energy supply through "slow release in the upper digestive tract and fermentation in the lower digestive tract". In vitro experiments show that the butyric acid concentration produced by the composition reaches 8.5±1.2mmol / L, which is 3.0 times that of resistant starch alone and 9.4 times that of probiotic alone, showing significant synergistic effects.

[0020] 2. Improve the colonization rate of probiotics and achieve targeted regulation of the gut microbiota. By using complex coagulation and encapsulation technology, the survival rate of probiotics in the gastrointestinal tract is improved, and they are released at specific points in the proximal colon. They form a "substrate-microbe" symbiotic system with resistant starch, which increases the colonization abundance of target bacteria by ≥1.0 log CFU / g. Human trials showed that after 8 weeks of intervention, the production of Bifidobacterium, Lactobacillus and total SCFA in the feces of subjects was significantly increased, which significantly optimized the intestinal flora structure.

[0021] 3. Multi-target, whole-chain metabolic regulation, improving glucose and lipid metabolism and insulin resistance. The composition achieves multi-target intervention through a "quadruple regulatory mechanism" that balances energy, repairs the barrier, inhibits inflammation, and inhibits metabolic enzymes: the inhibition rates of α-glucosidase, pancreatic lipase, and cholesterol esterase are 76.3±4.5%, 68.5±3.8%, and 54.2±3.5%, respectively, which are significantly higher than those of single components. Human trials showed that after 8 weeks of intervention, subjects experienced a 15.3% reduction in fasting blood glucose, a 26.1% reduction in 2-hour postprandial blood glucose, a 45.5% reduction in HOMA-IR index, a 33.3% reduction in triglycerides, and a 23.2% reduction in total cholesterol, with significant improvement in insulin resistance and glucose and lipid metabolism disorders.

[0022] 4. Significantly improves obesity indicators, achieving safe weight loss. Targeting the core characteristics of central obesity, population trials showed that after 8 weeks of intervention, the experimental group lost an average of 4.8±1.2 kg, reduced body fat percentage by 2.4±0.6%, and reduced waist circumference by 5.8±1.5 cm, all of which were significantly better than the placebo group. The weight loss effect was due to the dual effect of "physical satiety + metabolic regulation" rather than simple calorie restriction, which is more in line with the needs of healthy weight loss.

[0023] 5. Extends satiety time and improves product compliance. By combining a gradient fermentation prebiotic system with a non-fermented water-holding and swelling component, a dual-gradient system of "rapid satiety-viscosity maintenance-gradient fermentation" was constructed, which extended the satiety maintenance time to 172±32 min, which is 37.6% higher than that of inulin alone and 75.5% higher than that of xylooligosaccharide alone. Human trials showed that the peak postprandial satiety increased by 37% and the duration was extended by 65%, and mild satiety was still maintained at 180 min, significantly reducing food intake.

[0024] 6. Reduce gastrointestinal adverse reactions, balancing safety and compliance. Through optimized ingredient compatibility and low-dose, high-efficiency design, the incidence of gastrointestinal adverse reactions was controlled at 26.7%, and all of them were mild physiological reactions such as bloating and increased flatulence, which could be relieved on their own in 3-5 days. Compared with existing high-dose dietary fiber products (intolerance rate >40%), it significantly improved long-term use compliance. The gradient fermentation system enabled subjects to achieve compliance of 92%, which is 35.3%-67.3% higher than that of single prebiotics.

[0025] 7. Optimize product sensory experience and industrialization feasibility By employing sensory optimization technologies such as electronic tongue flavor blending, off-flavor masking, and texture improvement, the "function-taste paradox" of functional foods has been resolved. The preparation process is simple, enabling industrial production of both powder and tablet dosage forms. Furthermore, the raw materials all meet national / industry standards, maintain stable activity during the shelf life, and are suitable for large-scale promotion.

[0026] 8. Significantly improved bioavailability of food-medicine homologous components By employing targeted processes such as ultrafine grinding, supercritical extraction, and microwave-assisted extraction, the dissolution rate and bioavailability of active ingredients from food and medicine homologous ingredients are improved, avoiding the waste of ingredients and poor efficacy caused by direct grinding, and allowing the synergistic effect of food and medicine homologous ingredients with probiotics and prebiotics to be fully realized. Attached Figure Description

[0027] Fig. 1 This study examines the changes in key monitoring indicators in the experimental and placebo groups before and 8 weeks after product use.

[0028] Fig. 2 The curves show the changes in the experimental group and the placebo group before and after taking the product for 8 weeks. Detailed Implementation

[0029] To better explain and facilitate understanding of the present invention, the present invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

[0030] The main technical solution of the present invention includes: a colon-targeted microecological regulation composition, the effective components of which are compounded by weight percentage of 5-95% component A, 1-15% component B and 4-94% component C; Component A is resistant starch with a degree of polymerization (DP) ≥ 15 and a crystallinity ≥ 35%. Component B is a probiotic, encapsulated using coagulation or extrusion-gel methods with an encapsulation rate ≥75%; its tolerance to overdigestion is satisfied: survival rate ≥60% after 2 hours of treatment in simulated gastric juice and ≥50% after 4 hours of treatment in simulated intestinal juice; Component C contains functional nutritional excipients; the functional nutritional excipients include prebiotics and food-medicine homologous compositions; the prebiotics include fast-fermenting prebiotics, medium-fermenting prebiotics, slow-fermenting prebiotics, and non-fermented water-holding and swelling components.

[0031] The core of this invention is the construction of a ternary synergistic network of "carbon source sustained release - microbial community targeting - metabolic regulation" to achieve the technical goals of precise regulation of the entire digestive tract and multi-target metabolic intervention. The synergistic effect of the three forms a positive feedback loop, specifically as follows: Synergistic effect of component A on component B: Resistant starch ferments in the colon to produce short-chain fatty acids (SCFAs) such as butyric acid, which lowers the local pH of the colon to 5.8-6.2, creating an optimal environment for the survival and proliferation of probiotics. At the same time, it increases the expression level of butyric acid synthesis-related genes in probiotics by 1.5-2.5 times and the proliferation rate by 1.2-1.8 times, forming a positive feedback loop of "carbon source driven - microbial community expansion". Synergistic effect of component B on component C: β-galactosidase produced by probiotic fermentation can decompose prebiotics (such as xylooligosaccharides) to generate more bifidogenic factors. At the same time, acetic acid and propionic acid metabolized by probiotics can synergistically activate the AMPK signaling pathway of food and medicine homologous ingredients (such as Poria cocos polysaccharide), enhance insulin sensitivity, and achieve the synergistic effect of "microbial metabolism-active ingredient enhancement". Synergistic effect of component C on component A: The high molecular weight prebiotics in component C encapsulate resistant starch particles in the stomach, slowing down their disintegration rate and increasing the retention rate of resistant starch in the upper digestive tract by 15-25%; at the same time, soluble dietary fiber and resistant starch synergistically form a three-dimensional gel network, enhancing physical satiety and prolonging gastric emptying time by 10-20%, achieving the effect of "excipient protection and sustained release synergistic effect".

[0032] Components A, B, and C work together to overcome the limitations of single-component effects, achieving the triple technical goals of "slow-release energy supply in the upper digestive tract, targeted colonization of gut microbiota, and whole-chain metabolic regulation." Compared to single-component or binary combinations, butyric acid production, probiotic colonization rate, and digestive enzyme inhibition rate all achieve synergistic effects that are not simply additive.

[0033] Component A (resistant starch, DP≥15, crystallinity≥35%): resistant starch with high degree of polymerization and high crystallinity is selected, with its resistance to digestion and colonic fermentation characteristics as the core considerations. High crystallinity makes it less susceptible to hydrolysis by digestive enzymes in the upper digestive tract, avoiding drastic fluctuations in postprandial blood glucose. The specific degree of polymerization ensures that it can be fermented by intestinal flora in the colon to produce butyrate, providing a dedicated carbon source for probiotics. At the same time, it acts as a slow-release carbon source to achieve spatiotemporally specific energy supply through "upper slow release and lower fermentation," solving the problem that the rapid digestion of carbohydrates in traditional meal replacements exacerbates insulin resistance.

[0034] Component B (encapsulated probiotics, encapsulation rate ≥75%, digestibility meets standards): Select encapsulated probiotics and set strict encapsulation and digestibility indicators. The core considerations are the gastrointestinal survival rate and colon targeting of probiotics. Encapsulation can protect probiotics from the acid, alkali and enzymatic damage of gastric juice and intestinal juice, solving the technical bottleneck of low colonization rate and low survival rate of commercially available probiotics. The digestibility indicator ensures that probiotics maintain high activity when they reach the colon, laying the foundation for targeted colonization of the gut microbiota.

[0035] Component C (functional nutritional excipients + pharmaceutical excipients, containing graded prebiotics + food-medicine homologous composition): The functional nutritional excipients of "prebiotics + food-medicine homologous composition" are selected to be combined with pharmaceutical excipients. The core considerations are the survival support of probiotics, the multi-target nature of metabolic regulation, and the formulation formability. Prebiotics provide nutritional substrates for probiotics, while food-medicine homologous components achieve multi-target effects such as improving insulin resistance, inhibiting inflammation, and regulating lipid metabolism. Pharmaceutical excipients ensure that the composition can be prepared into powder / tablets, taking into account both industrial production and ease of consumption, and solving the problems of limited target and poor product compliance of single intervention methods.

[0036] Preferably, the fast-fermenting prebiotic is selected from at least one of xylooligosaccharides, fructooligosaccharides, galactooligosaccharides, stachyose, and cottonseed oligosaccharides; the medium-fermenting prebiotic is selected from at least one of inulin, oat β-glucan, pectin, and gum arabic; the slow-fermenting prebiotic is selected from at least one of resistant dextrin, polydextrose, psyllium husk, and cellulose; and the non-fermented water-holding swelling component is selected from at least one of konjac flour, carrageenan, xanthan gum, and guar gum. Preferably, the mass ratio of the fast-fermenting, medium-fermenting, and slow-fermenting prebiotics to the non-fermented water-holding swelling component in component C is (1.0-3.5):(1.0-4.5):(1.0-3.0):(1.0-2.0); the core optimal ratio is 2.0:2.0:2.0:1.0.

[0037] This formulation is designed for precise coverage of the entire digestive tract, from the stomach to the small intestine to the proximal, midstream, and distal parts of the colon. It combines the requirements of a "four-dimensional gradient" of fermentation rate, molecular weight, water-holding capacity, and functional targeting to achieve a synergistic effect of rapid satiety, gradient fermentation, long-lasting sustained release, and low gastrointestinal discomfort. The considerations and benefits of the proportions of various prebiotic types are as follows: (1) Rapidly fermented prebiotics (1.0-3.5): The proportion is adapted to the microecological environment of the proximal colon. It can rapidly produce acid within 2 hours, lowering the colonic pH to 5.5-6.0, creating an acidic environment for probiotic colonization. At the same time, it rapidly proliferates beneficial bacteria such as Bifidobacteria, paving the way for medium and slow fermentation components. The proportion should not exceed 3.5 to avoid excessive gas production, which can cause bloating, flatulence, and other discomfort. If the proportion of rapid fermentation is too high (>3.5): the gas production rate is too fast, the local pH of the colon drops sharply, which can easily cause bloating, increased flatulence, and other gastrointestinal discomfort, reducing product compliance. If the proportion is too low (<1.0): it cannot quickly build an acidic environment, the probiotic colonization rate drops significantly, and the medium and slow fermentation components cannot play an effective role.

[0038] (2) Medium-speed fermentation prebiotics (1.0-4.5, highest proportion): As the core component of gradient fermentation, the highest proportion can connect the acidic environment of rapid fermentation, continuously providing energy for butyric acid-producing bacteria (such as Clostridium plasmids) in the mid-colon for 6-8 hours. At the same time, it forms a "viscous barrier layer" in the small intestine to inhibit fat absorption and delay gastric emptying, achieving the dual effect of "small intestinal metabolic regulation + mid-colon microbiota supply", which is the key to continuous fermentation throughout the colon. If the proportion of medium-speed fermentation prebiotics is too high (>4.5): the fermentation cycle is too long, leading to butyric acid accumulation in the mid-colon. At the same time, the small intestinal viscous barrier is too thick, which may affect the normal absorption of nutrients. If the proportion is too low (<1.0): it cannot connect the fast and slow fermentation components, resulting in a fermentation "gap", the continuous acid production effect of the whole colon is lost, and the microbiota regulation effect is greatly weakened.

[0039] (3) Slow-fermenting prebiotics (1.0-3.0): The proportion is adapted to the fermentation needs of the distal colon. It can continuously release butyrate for 12-24 hours, repair the tight junction protein of the intestinal epithelium, and at the same time encapsulate resistant starch particles to improve their retention rate in the upper digestive tract. The proportion should not be less than 1.0 to ensure that there is a continuous fermentation substrate in the distal colon and achieve full-segment repair of the intestinal barrier. If the proportion of slow-fermenting prebiotics is too high (>3.0): the overall fermentation rate is too slow, the release of butyrate is delayed, the repair effect of the distal intestinal barrier is lagging, and it is easy to compete with resistant starch for fermentation substrate, reducing the butyrate production efficiency of resistant starch; if the proportion is too low (<1.0): there is no continuous fermentation substrate in the distal colon, the repair of tight junction protein of the intestinal epithelium is insufficient, the improvement effect of intestinal barrier function is poor, and the inhibitory effect of chronic inflammation is weakened.

[0040] (4) Non-fermented water-holding and swelling components (1.0~2.0): Non-fermentable, with a proportion suitable for the physical satiety needs in the stomach, can form a 3D gel network in the stomach, prolonging gastric emptying time by 54-60%, and working synergistically with medicinal and edible ingredients such as Polygonatum polysaccharide to enhance the duration of satiety. The proportion should not exceed 2.0 to avoid excessive gel thickness causing stomach bloating and pain, thus balancing physical satiety and gastrointestinal tolerance. If the proportion of non-fermented water-holding and swelling components is too high (>2.0): the gel in the stomach is too viscous, delaying excessive gastric emptying and easily causing stomach bloating and indigestion; if the proportion is too low (<1.0): it cannot form an effective physical satiety gel network, the duration of satiety is greatly shortened, and there is no difference from traditional meal replacement products, so it cannot reduce food intake.

[0041] This formulation, verified through in vitro fermentation, animal models, and human trials, can increase butyric acid production efficiency by 77.8%, prolong satiety duration by 37.6%, reduce gas production discomfort score by 43.8%, and improve subject compliance to 92%, achieving the optimal effect of gradient fermentation.

[0042] Preferably, the food-medicine homology composition comprises one or more of the following: spleen-strengthening and dampness-eliminating substances, heat-clearing and dampness-resolving substances, digestion-aiding and food-medicine homology substances, bowel-moistening and laxative substances, phlegm-resolving and dampness-eliminating substances, qi-tonifying and yin-nourishing substances, and other food-medicine homology substances; the spleen-strengthening and dampness-eliminating substances are selected from at least one of Poria cocos, Coix seed, Dioscorea opposita, white hyacinth bean, and red adzuki bean; the heat-clearing and dampness-resolving substances are selected from lotus leaf, cassia seed, chrysanthemum, honeysuckle, and gardenia. At least one of the following: Food-derived substances for digestion and relieving food stagnation are selected from at least one of hawthorn, radish seed, malt, and chicken gizzard lining; Food-derived substances for promoting bowel movement and relieving constipation are selected from at least one of hemp seed, apricot kernel, mulberry, and black sesame; Food-derived substances for resolving phlegm and removing dampness are selected from at least one of tangerine peel, citron, perilla, ginger, and cinnamon; Food-derived substances for tonifying qi and nourishing yin are selected from at least one of polygonatum, polygonatum odoratum, wolfberry, lily, and sea buckthorn; Other food-derived substances are selected from at least one of sophora japonica flower, dandelion, and agastache rugosa.

[0043] The food-medicine homology compositions are selected according to six major functions: "strengthening the spleen and eliminating dampness, clearing heat and resolving dampness, promoting digestion and eliminating food stagnation, moistening the intestines and relieving constipation, resolving phlegm and eliminating dampness, and tonifying qi and nourishing yin." The core consideration is the core pathological characteristics of metabolic syndrome: "spleen deficiency, dampness accumulation, food stagnation, and inflammation." The aim is to achieve the technical effect of "multi-target synergistic intervention and balanced, unbiased drug properties." The enhancement mechanisms of each type are as follows: Spleen-strengthening and dampness-eliminating ingredients (such as Poria cocos and Coix seed): These are the core conditioning ingredients, targeting the core pathogenesis of "spleen deficiency and dampness accumulation" in metabolic syndrome. Poria cocos polysaccharides activate the AMPK pathway to improve insulin sensitivity, while Coix seed polysaccharides regulate the intestinal flora and reduce LPS entry into the blood. The two work together to achieve the basic function of "strengthening the spleen and eliminating dampness - improving insulin resistance", thus solving the root cause of metabolic disorders.

[0044] Heat-clearing and dampness-resolving ingredients (lotus leaf, cassia seed, etc.): Targeting the "chronic low-grade inflammation" characteristic of metabolic syndrome, lotus leaf alkaloids activate BAT heat production and inhibit fat synthesis, cassia seed anthraquinones promote intestinal peristalsis and detoxification, and chrysanthemum chlorogenic acid inhibits α-glucosidase. The three work together to achieve the effects of "clearing heat and removing dampness, anti-inflammation, lowering blood sugar, and reducing fat", targeting glucose and lipid metabolism disorders and inflammatory links.

[0045] Foods that aid digestion and reduce food stagnation (such as hawthorn and radish seeds): These products target the problems of "food stagnation and fat accumulation" in metabolic syndrome. Hawthorn flavonoids inhibit pancreatic lipase to reduce fat absorption, malt α-amylase inhibitors delay carbohydrate digestion, and chicken gizzard membrane bidirectionally regulates digestive function. Together, they achieve the effects of "aiding digestion and reducing food stagnation - reducing energy intake and improving digestive disorders," thereby lowering postprandial blood glucose and fat absorption.

[0046] Laxatives (such as hemp seed and mulberry): These products target the slowed intestinal motility and toxin accumulation in patients with metabolic syndrome. Hemp seed's unsaturated fatty acids lubricate the intestines, while mulberry's anthocyanins provide antioxidant benefits and promote the proliferation of bifidobacteria. Together, they achieve the effects of "laxatives - eliminating intestinal toxins and optimizing the gut microbiota structure," reducing the inflammatory response caused by toxins entering the bloodstream.

[0047] Phlegm-resolving and dampness-removing ingredients (such as tangerine peel and cinnamon): Targeting the problems of "phlegm-dampness obstruction and insulin resistance" in metabolic syndrome, hesperidin in tangerine peel inhibits the PI3K / Akt pathway to improve insulin resistance, while cinnamaldehyde enhances insulin sensitivity, synergistically achieving the effects of "resolving phlegm-dampness, regulating lipid metabolism, and improving insulin signal transduction".

[0048] Qi-tonifying and Yin-nourishing ingredients (such as Polygonatum sibiricum and Lycium barbarum): Targeting the "Qi and Yin deficiency" caused by the long-term development of metabolic syndrome, Polygonatum sibiricum polysaccharides bidirectionally regulate blood sugar, while Lycium barbarum polysaccharides upregulate SCFA receptor FFAR3, synergistically achieving the effects of "tonifying Qi and nourishing Yin - consolidating the metabolic regulation effect and enhancing the body's immunity", avoiding rebound after intervention.

[0049] Other food and medicine homologous substances (such as Sophora japonica and Taraxacum mongolicum): As auxiliary synergistic ingredients, Sophora japonica rutin improves vascular permeability, and Taraxacum mongolicum polysaccharides promote bile acid excretion, further making up for the shortcomings of the core category in vascular protection and lipid metabolism regulation, and achieving full-chain metabolic intervention.

[0050] The above six categories of food-medicine homologous substances are scientifically combined to achieve comprehensive conditioning of "strengthening the spleen, removing dampness, clearing heat, promoting digestion, relieving constipation, and nourishing yin" for multiple pathological aspects of metabolic syndrome. At the same time, it ensures the mildness of the medicinal properties and avoids gastrointestinal discomfort caused by excessive amounts of a single type of ingredient (such as excessive cooling of heat-clearing ingredients or excessive richness of tonifying ingredients). It achieves "synergistic efficacy and balanced medicinal properties" and improves the safety and compliance of the product.

[0051] Preferably, the formulation further includes pharmaceutical excipients, which include a binder, a lubricant, and a disintegrant; the binder is at least one selected from sorbitol, maltodextrin, microcrystalline cellulose, lactose, compressible starch, polyethylene oxide, and povidone; the lubricant is at least one selected from magnesium stearate, stearic acid, calcium stearate, and silicon dioxide; and the disintegrant is at least one selected from sodium carboxymethyl starch and dry starch.

[0052] Preferably, the food-medicine homologous substances in component C are treated to improve bioavailability using one or more of the following methods: ultrafine pulverization and cell wall disruption, low-temperature extraction, supercritical CO2 extraction, and microwave-assisted extraction; the prebiotics are modified using one or more of the following methods: microencapsulation, molecular weight fractionation, oxidative cross-linking, and mineral chelation. Treating the food-medicine homologous substances and prebiotics according to the aforementioned methods can improve the bioavailability of active ingredients, optimize the functional properties of raw materials, and enhance synergy with other components, thus solving the problems of low dissolution rate of active ingredients, mismatched functional properties, and poor synergistic effects caused by traditional direct addition.

[0053] For plant-based raw materials such as Poria cocos and Dioscorea opposita, ultra-fine pulverization and cell wall disruption are employed to increase the dissolution rate of active ingredients (such as Poria cocos polysaccharides and Dioscorea opposita mucoprotein) by more than 30%, significantly improving bioavailability and preventing the body from being unable to absorb and utilize active ingredients due to cell wall encapsulation. For heat-sensitive raw materials such as Coix lacryma-jobi and Polygonatum sibiricum, low-temperature extraction of active ingredients avoids the degradation of active ingredients such as polysaccharides and saponins caused by high temperatures, ensuring the bioactivity of the raw materials while preserving their inherent flavor. For raw materials containing volatile active ingredients such as Chrysanthemum and Citrus peel, supercritical CO2 extraction is used under low temperature and high pressure to efficiently extract volatile components (such as chrysanthemum chlorogenic acid and Citrus peel hesperidin) without organic solvent residue, improving product safety and the purity of active ingredients. For raw materials such as Cassia tora and Radish seeds, microwave-assisted extraction is used, utilizing the thermal and non-thermal effects of microwaves to accelerate the release and dissolution of intracellular active ingredients, increasing extraction efficiency by 20-40% while shortening extraction time and reducing industrial production costs. Various processing methods can be adapted to the characteristics of different food and medicine homologous raw materials as needed, so as to achieve efficient retention of active ingredients, improved dissolution rate, and optimized bioavailability, and fully exert the synergistic effect of food and medicine homologous ingredients with probiotics and prebiotics.

[0054] For rapidly fermenting prebiotics such as xylooligosaccharides and fructooligosaccharides, encapsulation can slow down their fermentation in the stomach and small intestine, ensuring they are released only after reaching the colon, improving colonic targeting, and avoiding gastrointestinal discomfort caused by rapid gas production in the proximal digestive tract. For prebiotics such as inulin and oat β-glucan, molecular weight fractionation is used to screen for oat β-glucan and long-chain inulin (DP≥23) with 200-500kDa, ensuring their functional characteristics of forming a viscous barrier in the small intestine and undergoing moderate-speed fermentation in the colon, while eliminating ineffective low-molecular-weight components and improving the functional efficiency of prebiotics. For prebiotics such as pectin, oxidative cross-linking can enhance their gel properties, synergistically forming a more stable intestinal mucosal barrier with yam mucoprotein, improving the intestinal barrier repair effect. For prebiotics such as galactooligosaccharides, chelation with minerals such as calcium and zinc can promote the secretion of β-galactosidase by probiotics, decomposing prebiotics to produce more bifidogenic factors, while achieving slow release of minerals and improving mineral absorption and utilization. Various processing methods precisely modify the fermentation rate and functional targets of prebiotics to achieve "enhanced colon targeting, optimized functional properties, and enhanced synergy with probiotics / resistant starch," ensuring the precise implementation of the gradient fermentation system.

[0055] Preferably, the resistant starch of component A is a polysaccharide or its derivative consisting of D-glucose units linked by α-1,4 and / or α-1,6 glycosidic bonds, and its resistance is enhanced by wet heat modification; the digestibility of component A is ≤30% based on the small intestinal digestibility determined by the ISO 26642:2010 method. Component B is one or a combination of two or more strains of Bifidobacterium, Lactobacillus, and Clostridium butyricum.

[0056] The resistant starch of component A undergoes wet-heat modification treatment, with the core consideration of improving its resistance to digestion, colonic fermentation characteristics, and synergy with other components. This addresses the problems of insufficient resistance to digestion and low butyric acid production efficiency of natural resistant starch. The specific effects are as follows: (1) Improved resistance to digestion: Moist heat modification makes the crystalline structure of resistant starch more stable, and some amylose rearranges to form crystalline regions that resist digestion. The small intestinal digestibility measured by ISO 26642:2010 method is further reduced to ≤30%, and the resistance to hydrolysis in the upper digestive tract is significantly improved. The peak blood glucose level after meals is reduced by 20-40%, and the area under the blood glucose curve is reduced by 15-30%, which can more effectively avoid drastic fluctuations in blood glucose after meals and improve insulin resistance.

[0057] (2) Optimize colonic fermentation characteristics: wet heat modification makes the molecular structure of resistant starch more easily utilized by colonic flora, and the efficiency of fermentation to produce butyric acid is increased by more than 40%. The proportion of butyric acid produced in the total SCFA is ≥15% within 24 hours, and the peak concentration of butyric acid is ≥5mmol / L and maintained for ≥4 hours, providing more sufficient exclusive carbon source for probiotics and enhancing the proliferation and butyric acid production activation effect of probiotics.

[0058] (3) Enhanced synergy with other components: The water-holding capacity of the resistant starch after wet-heat modification increased to 8.5±1.2 mL / g, forming a more stable three-dimensional gel network in synergy with the non-fermented water-holding and swelling components in component C. The physical satiety was significantly enhanced, and the synergistic effect of its fermentation product butyric acid with probiotics and food-medicine homologous components was more significant, further improving insulin sensitivity and anti-inflammatory effects. The wet-heat modification treatment enabled the core function of the resistant starch as a slow-release carbon source to be effectively exerted, becoming the basis of the ternary synergistic system and laying the carbon source foundation for the targeted colonization of the microbial community and the whole-chain metabolic regulation.

[0059] In a preferred embodiment of the present invention, strains of Bifidobacterium, Lactobacillus, and Clostridium butyricum are used individually or in combination. The core considerations are the colonic colonization, functional targeting, and synergy of the strains, which match the pathological characteristics of metabolic syndrome, namely "dysbiosis, insulin resistance, chronic inflammation, and insufficient butyrate production." The specific benefit mechanism is as follows: Bifidobacterium: a dominant beneficial bacterium in the proximal colon, can be directed to proliferate by rapidly fermentable prebiotics, significantly improve the diversity of intestinal flora, reduce opportunistic pathogens, and metabolize to produce acetic acid and propionic acid, which synergistically activate the AMPK pathway of food and medicine homologous ingredients, improve insulin sensitivity. Human trials have shown that it can increase the abundance of Bifidobacterium by ≥1.0 log CFU / g.

[0060] Lactobacillus: It has strong digestive resistance and can colonize the entire colon, inhibiting harmful bacteria such as Escherichia coli in the intestine, reducing chronic low-grade inflammation caused by LPS entering the blood. At the same time, its metabolites can work synergistically with hawthorn flavonoids and lotus leaf alkaloids to inhibit the activity of lipase and reduce fat accumulation.

[0061] Clostridium butyricum: The core butyric acid-producing bacterium, which can directly synthesize butyric acid. It has a synergistic effect with the fermentation products of resistant starch, which increases the concentration of butyric acid in the colon by more than 3.2 times. Butyric acid can repair tight junction proteins in intestinal epithelium, inhibit HDAC3 to reduce inflammatory response, and at the same time provide energy for colon cells and improve intestinal peristalsis.

[0062] When Bifidobacterium and Clostridium butyricum / Lactobacillus are used in combination, a synergistic effect of "colonization-acid production-anti-inflammation" can be achieved: Bifidobacterium rapidly colonizes and lowers colonic pH, creating a suitable environment for Clostridium butyricum / Lactobacillus; Clostridium butyricum produces a large amount of butyrate to repair the intestinal barrier and improve insulin resistance; Lactobacillus inhibits inflammation throughout the process. The three complement each other, doubling the effect of gut microbiota regulation and metabolic regulation compared to single strains. The selection and combination of strains perfectly match the design of the slow-release carbon source-probiotic symbiotic system, solving the problems of single function and insufficient butyrate production in commercially available probiotic products, and achieving synergistic functional remodeling and metabolic regulation of the gut microbiota.

[0063] Secondly, the present invention provides the application of the above-mentioned colon-targeted microecological regulation composition in the preparation of functional foods for the intervention of metabolic syndrome.

[0064] Preferably, the functional food has one or more of the following effects: improving insulin resistance, optimizing intestinal flora structure, increasing the production of short-chain fatty acids in the intestine, regulating glucose and lipid metabolism, reducing body fat percentage, reducing waist circumference, repairing the intestinal mucosal barrier, and prolonging satiety time.

[0065] Preferably, for individuals with hyperglycemia, the effective components of the colon-targeted microecological regulation composition include component A (80-95%), component B (1-10%), and component C (4-10%); for individuals with comprehensive metabolic disorders, the effective components of the colon-targeted microecological regulation composition include component A (54-72%), component B (6-15%), and component C (22-35%).

[0066] Differentiated group ratios were designed for individuals with hyperglycemia and those with comprehensive metabolic disorders, taking into account the pathological characteristics and intervention priorities of different populations, to achieve precise, targeted, and highly effective personalized interventions, as detailed below: (a) For people with high blood sugar (A: 80-95%, B: 1-10%, C: 4-10%) The core pathological problems in people with hyperglycemia are insulin resistance and large fluctuations in postprandial blood glucose. The focus of intervention is to lower postprandial blood glucose, improve insulin sensitivity, and reduce the rapid absorption of carbohydrates. The technical effects of this formula are as follows: ① High proportion of component A: 80-95% of wet-heat modified resistant starch serves as the core slow-release carbon source, maximizing its resistance to digestion and reducing postprandial blood glucose response by 30-50%. This avoids the rapid rise and fall of blood glucose caused by the rapid digestion of carbohydrates, thereby improving insulin resistance from the root. At the same time, its colonic fermentation to produce butyric acid can work synergistically with a small amount of probiotics to improve the intestinal flora and assist in lowering blood sugar.

[0067] ② Low proportion component B: 1-10% probiotics can maintain the balance of the basic intestinal flora, avoid the monotony of intestinal flora caused by a high proportion of resistant starch, and at the same time, a small amount of probiotic metabolites can help improve insulin sensitivity. Moreover, the low proportion will not cause gastrointestinal discomfort due to gas production from probiotic fermentation.

[0068] ③ Extremely low proportion of component C: Component C, at 4-10%, retains only a small amount of excipients for formulation, avoiding the additional carbohydrate intake from food-grade ingredients and prebiotics, ensuring the purity of the hypoglycemic effect, and avoiding the influence of excipients on blood sugar. This formulation achieves precise intervention "with slow-release carbon source for hypoglycemic control as the core and probiotics assisting in regulating the gut microbiota." An 8-week intervention can reduce fasting blood glucose by 15.3%, postprandial 2-hour blood glucose by 26.1%, and HOMA-IR index by 45.5%, significantly improving glucose metabolism disorders in hyperglycemic individuals.

[0069] (ii) Individuals with comprehensive metabolic disorders (A: 54-72%, B: 6-15%, C: 22-35%) The core pathological problems in individuals with comprehensive metabolic disorders are central obesity, insulin resistance, glucose and lipid metabolism disorders, gut microbiota dysbiosis, and chronic inflammation. The intervention focuses on multi-target synergistic intervention, remodeling the gut microbiota, regulating energy metabolism, and reducing fat accumulation. The technical effects of this combination are as follows: ① Medium proportion component A: 54-60% resistant starch not only ensures slow-release energy supply and reduces postprandial blood glucose, but also provides sufficient carbon source for high proportion of probiotics, achieving the dual effect of "blood sugar reduction + bacterial carbon source".

[0070] ② High proportion of component B: 6-15% probiotics provide sufficient bacterial sources for gut microbiota remodeling, and work synergistically with gradient prebiotics to achieve targeted colonization of the microbiota, increasing Bifidobacterium and Lactobacillus by 1.8 log CFU / g and total SCFA production by 2.6 times, thereby improving the microbiota imbalance from the root.

[0071] ③ High proportion of component C: 22-35% of component C contains gradient prebiotics and all categories of food and medicine homologous ingredients. Prebiotics achieve gradient fermentation and long-lasting satiety, while food and medicine homologous ingredients achieve multi-target metabolic regulation. Together with probiotics and resistant starch, they achieve comprehensive intervention of "lowering blood sugar, reducing fat, anti-inflammation, promoting bowel movement, and increasing satiety". An 8-week intervention can result in an average weight loss of 4.8±1.2kg, a waist circumference reduction of 5.8±1.5cm, and a body fat percentage reduction of 2.4±0.6%. At the same time, glucose and lipid metabolism and inflammatory indicators are significantly improved.

[0072] The two formulations mentioned above achieve the technical goal of "three-element synergy and multi-target full-chain intervention", solving the problem of single intervention methods and poor effects in people with comprehensive metabolic disorders, and achieving comprehensive improvement in weight, blood sugar, blood lipids and gut microbiota.

[0073] The specifications of each raw material are as follows: 1. Probiotic strains: The strains belong to the Bacteria domain and are listed in the "List of Microbial Strains that Can Be Used in Food" (National Health Commission 2022 Edition), the EU QPS List, or the US FDA GRAS List; whole genome sequencing has been completed, confirming the absence of hemolytic genes, transferable antibiotic resistance genes, and virulence factors. The probiotics are added via complex coagulation or extrusion-gel encapsulation, with an encapsulation rate ≥75%. Tolerance to perdigestion: Survival rate ≥60% after 2 hours of treatment in simulated gastric juice and ≥50% after 4 hours of treatment in simulated intestinal juice. In the final product, the live bacteria count is ≥1×10⁻⁶ within the shelf life. 9 CFU / g (for powder) or ≥5×10 9 CFU / g (for tablets).

[0074] 2. Raw material technical standards (Table 1)

[0075]

[0076] The present invention will be further described in detail below with reference to specific embodiments. The scope of protection of the present invention is not limited to the following embodiments, and all technical solutions based on the present invention are within the scope of protection of the present invention.

[0077] Example 1 This embodiment provides a colon-targeted microecological regulation composition powder suitable for people with hyperglycemia, the active ingredient composition of which is as follows: Component A: 90% wet-heat modified resistant starch (DP≥15, crystallinity≥38%).

[0078] Component B: A complex of Bifidobacterium lactis and Clostridium butyricum encapsulated (commercially available strains, 1:1 ratio, encapsulated using coagulation method, encapsulation rate 80%, 65% survival rate in simulated gastric juice after 2 hours, 55% survival rate in simulated intestinal juice after 4 hours, viable count ≥ 1.2 × 10⁻⁶). 9 (CFU / g). Component B accounts for 4% based on the dry weight of probiotics.

[0079] Component C: xylooligosaccharide 0.5% (DP2-4 content ≥88%, purity ≥92%), oat β-glucan 0.5%, inulin 0.5%, polydextrose 0.5%, konjac powder 0.5% (prebiotic microencapsulation modification), Poria cocos (ultra-fine pulverization and cell wall breaking) 2%, hawthorn 1.5% (all pretreated).

[0080] Preparation method: (1) The resistant starch was modified by wet heat (121℃, 20min, moisture 30%), dried and pulverized, and passed through a 100-mesh sieve. The "compound bacteria of Bifidobacterium lactis + Clostridium butyricum" was encapsulated by gelatin-gum arabic as the wall material and the core-to-wall ratio was 1:3 by coagulation method to obtain probiotics. (2) Premixing: The probiotics and component C were premixed to obtain premixed powder to ensure uniformity of mixing. (3) Total mixing: The modified resistant starch and premixed powder were put into a three-dimensional mixer and mixed for 20min. The uniformity of mixing was ≥96%. (4) Packaging: The total mixture was packaged into 10g / strips using a packaging machine and sealed to obtain the powder composition.

[0081] Test Experiment 1 The powder composition of Example 1, component A, and component B were subjected to an in vitro simulation experiment. The experimental method was as follows: I. Preparation of Experimental Materials (a) Sample preparation Component A sample: Wet heat modified resistant starch (meeting the technical standards of this invention: DP≥15, crystallinity≥35%, small intestinal digestibility≤30%), prepared by in vitro simulated gastrointestinal digestion (removing the digestible part of the upper digestive tract and simulating the substrate that actually reaches the colon), and finally prepared to a concentration of 100mg / mL.

[0082] Component B sample: encapsulated probiotics (re-aggregation / extrusion-gel encapsulation, encapsulation rate ≥75%, preferably Bifidobacterium lactis + Clostridium butyricum complex), after in vitro simulated gastrointestinal digestion treatment, the final concentration was adjusted to 1×10 9 CFU / mL.

[0083] Composition sample: The sample of Example 1 was subjected to the same in vitro gastrointestinal digestion treatment, and the final concentration was matched with the equivalent amount of the single component (to ensure that the carbon source and bacterial count are consistent with the single component).

[0084] Blank sample: Colon fermentation medium without the test sample.

[0085] (II) Core Reagents Colonic fermentation medium (simulating colonic nutrient environment): peptone 5g / L, yeast extract 2g / L, tryptone 5g / L, bile salts 0.5g / L, K2HPO4 1g / L, KH2PO4 0.5g / L, MgSO4·7H2O 0.1g / L, CaCl2·2H2O 0.05g / L, FeSO4·7H2O 0.001g / L, resazurin 0.001g / L, cysteine ​​hydrochloride 0.5g / L (anaerobic reducing agent), distilled water to a final volume of 1L, initial pH adjusted to 7.0±0.1, autoclaved at 121℃ for 20min, cooled and aseptically added to the anaerobic reducing agent; Diluent / buffer: 0.1 mol / L PBS buffer (pH 7.0), sterile physiological saline (0.9% NaCl); Bacterial isolation / counting reagents: MRS medium (Lactobacillus / Bifidobacterium counting), TSA medium (total bacterial count), Clostridium butyricum-specific medium; Short-chain fatty acid (SCFA) detection reagents: acetic acid, propionic acid, butyric acid standards (purity ≥99%), methanol (chromatographic grade), phosphoric acid (analytical grade), ultrapure water; In vitro gastrointestinal digestion reagents: simulated gastric juice (0.2% NaCl, 0.32% pepsin, 3000 U / mg, pH adjusted to 3.0±0.1 with 0.1 mol / L HCl), simulated intestinal juice (0.1 mol / L PBS buffer, containing 1% trypsin, 250 U / mg, pH adjusted to 7.5±0.1).

[0086] (III) Experimental Instruments Anaerobic culture system: anaerobic incubator (containing N2:H2:CO2=80:10:10 anaerobic gas), anaerobic tubes / anaerobic bottles; Digestion culture equipment: constant temperature water bath shaker (37℃±0.5℃), constant temperature incubator; Detection instruments: high performance liquid chromatograph (HPLC, for SCFA quantification), enzyme reader / colony counter (for bacterial count), precision pH meter (accuracy 0.01); Pretreatment equipment: high-speed refrigerated centrifuge (10000r / min), ultra-clean workbench, vortex shaker, pipettes (100μL / 1mL / 5mL), sterile centrifuge tubes / test tubes.

[0087] (iv) Human fecal microbial solution (simulating the core microecology of the colon) Donor selection: 3 healthy adults (20-40 years old) who have not taken probiotics, antibiotics, or dietary fiber supplements in the past 3 months and have regular diets; Preparation of bacterial suspension: Take fresh fecal samples (within 1 hour), add sterile physiological saline containing anaerobic reducing agent at a ratio of 1:5 (w / v), vortex for 3 minutes to obtain a uniform suspension, filter through 4 layers of sterile gauze to remove residues, and quickly transfer the fecal bacterial suspension to an anaerobic incubator under aseptic conditions for later use (anaerobic operation throughout).

[0088] II. Pretreatment: In vitro simulation of gastrointestinal digestion To simulate the digestion process of the test samples through the human stomach and small intestine, only the effective components reaching the colon are retained to ensure the authenticity of the experiment. The procedure is as follows: Take 10 mL of each test sample (component A, B, and the combination), add an equal volume of simulated gastric juice, and treat in a constant temperature water bath at 37°C with shaking (100 r / min) for 2 h (simulating gastric digestion); adjust the pH of the above system to 7.5±0.1 with 1 mol / L NaOH, add an equal volume of simulated intestinal juice, and continue to treat in a constant temperature water bath at 37°C with shaking (100 r / min) for 4 h (simulating small intestinal digestion); after digestion, centrifuge at 4°C and 5000 r / min for 10 min, discard the supernatant (to remove the gastric-small intestinal digestion products), wash the precipitate twice with sterile PBS buffer, resuspend and bring the volume to the original volume to obtain the colon fermentation test sample (simulating the substrate / live bacteria that actually reach the colon), for later use.

[0089] III. In vitro colonic fermentation experiment procedure The operation is completed in a clean bench and anaerobic incubator, strictly ensuring an anaerobic environment (avoiding contamination by other bacteria and the inhibition of beneficial / acid-producing bacteria by oxygen), and is divided into three stages: inoculation, cultivation, and sampling. (a) Inoculation: Take a sterile anaerobic bottle, add 40 mL of sterilized colon fermentation medium to each bottle, and place it in an anaerobic incubator for 2 h to equilibrate (to ensure the medium is anaerobic); add human fecal bacterial suspension at a ratio of 10% (v / v), and then add 5 mL of the pretreated colon fermentation test sample (component A, component B, and combination) respectively. Add 5 mL of sterile PBS buffer to the blank control; after gently mixing, seal the anaerobic bottle with a sterile rubber stopper, and introduce anaerobic gas (N2:H2:CO2=80:10:10) for 1 min to ensure the anaerobic environment inside the bottle, and label the groups (component A group, component B group, combination group, and blank control group).

[0090] (ii) Cultivation: All anaerobic bottles were placed in a constant temperature water bath incubator at 37℃±0.5℃ for static anaerobic cultivation for 24h (simulating the colon fermentation cycle; the core focus of this invention is on acid production and changes in the microbial community over 24h). No shaking was performed during the cultivation process to ensure sufficient contact between the microbial community and the substrate.

[0091] (III) Sampling: Samples were taken at five time points: 0h (initial), 4h, 8h, 12h, and 24h of culture. Three parallel samples were set up for each group. The sampling volume was 2mL / time. The operation was as follows: Under aseptic conditions, the rubber stopper of the anaerobic bottle was opened, and 2mL of fermentation broth was taken with a sterile pipette and quickly transferred to a sterile centrifuge tube. 1mL was used for pH measurement: the pH value of the fermentation broth was measured immediately with a precision pH meter and the data was recorded. The other 1mL was divided into two parts, which were used for bacterial count and SCFA content detection, respectively. Pretreatment was performed immediately to avoid sample deterioration.

[0092] IV. Sample Testing and Index Determination (a) Intestinal flora count (mainly Bifidobacteria) The number of Bifidobacteria in the fermentation broth (log CFU / mL) was determined using the plate count method, reflecting the proliferative capacity of the bacterial community. The sampled fermentation broth was serially diluted 10-fold with sterile physiological saline (10-10). -1 ~10 -8 Take 100 μL of bacterial culture at each dilution, spread it evenly on MRS Bifidobacterium-specific medium plates, and incubate in an anaerobic incubator at 37°C for 48 h. After the incubation, select plates with colony counts between 30 and 300, count the colonies, calculate the number of Bifidobacteria per milliliter of fermentation broth, convert it to log CFU / mL, and take the average of 3 parallel samples.

[0093] (II) Determination of Short-Chain Fatty Acid (SCFA) Content High-performance liquid chromatography (HPLC) was used to quantitatively determine the concentrations (mmol / L) of acetic acid, propionic acid, and butyric acid in the fermentation broth, which were the core detection indicators. The chromatographic conditions and pretreatment were as follows: (1) Sample pretreatment: Take 1 mL of fermentation broth, add 1 mL of chromatographic grade methanol, vortex for 1 min, centrifuge at 4℃ and 10000 r / min for 15 min, take the supernatant, filter through a 0.22 μm organic phase filter membrane to obtain the HPLC detection sample; (2) Preparation of standard curve: Prepare standard solutions of acetic acid, propionic acid and butyric acid (concentration gradient: 0.1, 0.5, 1, 5, 10 and 20 mmol / L respectively), process them according to the above pretreatment method, and perform HPLC detection. Plot the standard curve with concentration as the abscissa and peak area as the ordinate, and calculate the regression equation. (3) HPLC chromatographic conditions: Column: C18 reversed-phase column (250mm×4.6mm, 5μm); Mobile phase: 0.05mol / L phosphoric acid aqueous solution: methanol = 95:5 (v / v), flow rate 1.0mL / min; Column temperature: 30℃; Detection wavelength: 210nm; Injection volume: 20μL; (4) Sample determination: Inject the treated sample into the HPLC instrument, record the peak area, calculate the concentrations of acetic acid, propionic acid and butyric acid according to the standard curve regression equation, and take the average value of 3 parallel samples.

[0094] Each group in the above experiments had 3 parallel samples, and the entire experiment was independently repeated 3 times to ensure the reliability and reproducibility of the experimental results. SPSS / GraphPad Prism software was used for data analysis, and the mean ± standard deviation (x ± s) of each index was calculated. One-way ANOVA was used to analyze the differences between groups, and P < 0.05 was used to indicate that the difference was statistically significant. The concentrations of acetic acid, propionic acid, and butyric acid, the proliferation of Bifidobacterium (log CFU / mL), and the final pH value of the system were counted after 24 hours of incubation in each group. The differences between the combined group and the single component were compared and analyzed to verify the synergistic effect.

[0095] VI. Experimental Results The experimental results are shown in Table 2.

[0096]

[0097] As shown in Table 2, the butyric acid concentration of the combined group (8.5±1.2 mmol / L) was significantly higher than the sum of the concentrations of group A and group B, and was more than 3 times that of group A (2.8±0.6 mmol / L) and more than 1.5 times that of group B (0.9±0.3 mmol / L). The proliferation of Bifidobacteria in the combined group (log value increase) was ≥1.0 log CFU / mL, which was significantly higher than that of the single component. The final pH of the fermentation system of the combined group dropped to between 5.5 and 6.0, which was 0.8-1.1 units lower than that of the single component, providing the optimal fermentation environment for butyric acid producing bacteria. The differences between the above indicators were all statistically significant (P<0.01), which confirms that the substrate-microbial community positive feedback mechanism is established.

[0098] Test Experiment 2 Furthermore, comparative experiments were conducted on component C of Example 1 or its prebiotics to assess acid production, gas production, and maintenance of satiety. The experimental methods are as follows: 1. Experimental Grouping Single inulin group, single xylooligosaccharide group, gradient prebiotic system group (component C of Example 1), and blank group. 2. Module-based testing Module 1: Colonic Gradient Fermentation Detection Anaerobic culture at 37℃ for 24 hours was performed, and samples were taken precisely from the colon (proximal 0-4h / mid section 4-12h / distal section 12-24h). Butyric acid production, bacterial proliferation, and pH were measured at each time point, and fermentation kinetic curves were plotted to verify continuous acid production throughout the colon.

[0099] Module 2: Water Holding Power / Viscosity Testing The water-holding capacity, swelling capacity, 1-hour viscosity, and viscosity retention rate of each group in the gastric phase (pH 3.0), small intestinal phase (pH 7.5), and colonic phase (pH 6.0) were measured according to national standards to verify the gradient satiety characteristics.

[0100] Module 3: Human Sensory Evaluation Twenty healthy volunteers / groups took 10g of sample (powder) on an empty stomach and were scored using a 7-point scale: Satiety: scored at intervals from 0 to 180 minutes, and the duration of satiety was recorded. Gas Discomfort: scored within 24 hours (0-10 points), and the average score was recorded. Compliance: taken for 7 consecutive days, and the actual consumption rate was calculated.

[0101] Module 4: Digestive Enzyme Inhibition Detection The inhibition rates of α-glucosidase and pancreatic lipase in each group were measured by colorimetric method to verify the targeted regulation of glucose and lipid metabolism.

[0102] 3. Result Determination Compared with the single prebiotic group, the gradient group showed a ≥30% increase in satiety time, a ≥70% increase in butyrate production efficiency, a ≥40% decrease in gas production discomfort score, and a ≥30% increase in compliance, confirming the effectiveness of the four-dimensional gradient design.

[0103] All in vitro fermentations were performed under anaerobic conditions, with constant temperature incubation at 37°C. Samples were analyzed immediately after sampling. The gastrointestinal digestion pretreatment consisted of: simulating gastric juice for 2 hours → adjusting pH → simulating intestinal juice for 4 hours → centrifugation and washing, retaining only the effective components reaching the colon. SCFA detection was performed using HPLC (C18 column, 210nm detection), and bacterial counts were performed using the plate plating method. Data were taken as the mean ± standard deviation of three parallel samples. (Gastrointestinal digestion pretreatment, colonic fermentation medium, HPLC SCFA measurement, and plate bacterial counts are the same as in Experiment 1, "II. Pretreatment: In Vitro Simulated Gastrointestinal Digestion").

[0104] The experimental results are shown in Table 3.

[0105] Table 3: Comparison of the effects of gradient fermentation and single prebiotics

[0106] Table 3 shows the following: Fermentation and Acid Production: The butyric acid production efficiency of the gradient group was 3.2 times that of the control group, and 77.8% higher than that of the single inulin group (1.8 times). It could continuously produce butyric acid for 24 hours, breaking through the time window limitation of single prebiotics. Satiety Effect: The satiety maintenance time of the gradient group was 172 min, 37.6% longer than that of the single inulin group (125 min), and the satiety AUC increased by 83.9%. Gastrointestinal Discomfort: The gas production discomfort score of the gradient group was 1.8 points, 43.8% lower than that of the single inulin group (3.2 points), with no serious discomfort. Compliance: The 7-day compliance rate of the gradient group was 92%, 35.3% higher than that of the single inulin group (68%). Microbial Proliferation: The Bifidobacteria in the gradient group increased by 1.9 log CFU / g, significantly higher than that of the single xylooligosaccharide group (0.6 log) and the single inulin group (0.8 log), achieving targeted proliferation of microbiota throughout the colon.

[0107] Test Experiment 3 An in vitro α-glucosidase inhibition experiment was conducted on equal amounts of the composition of Example 1, component A, component B, and component C.

[0108] The in vitro experimental method for α-glucosidase inhibitory activity is as follows: Take 200 μL of sample solutions of different concentrations and 200 μL of α-glucosidase solution (1.5 U / mL), mix well, and incubate at 37℃ for 5 min. Add 200 μL of PNPG solution (2.5 mmol / L), mix well, and continue incubating at 37℃ for 15 min. Add 800 μL of Na2CO3 solution (0.2 mol / L) to terminate the reaction, and measure the absorbance value at 405 nm using a microplate reader.

[0109] In vitro experiment to determine the inhibitory activity of pancreatic lipase: 0.1 mL of porcine pancreatic lipase (1 mg / mL, freshly prepared) was mixed with 0.2 mL of sample solutions of different concentrations, and Tris-HCl buffer (pH 8.0) was added to a total volume of 1 mL. The mixture was incubated at 37 °C for 15 min, and then 0.1 mL of acetonitrile substrate solution was added. The mixture was thoroughly mixed and incubated at 37 °C for another 30 min. The absorbance was measured at 410 nm using a microplate reader.

[0110] In vitro experiment to determine the inhibitory activity of cholesterol esterase: Cholesterol esterase solution (5 mU / mL) was mixed with sample solutions of different concentrations and pre-incubated at 25°C for 10 min. Then, p-nitrophenyl butyrate substrate solution was added, mixed well, and incubated at 25°C for 30 min. The absorbance value was measured at 405 nm using an ELISA reader.

[0111] Calculation formula:

[0112] The results of the comparison of the inhibition rates of the compositions on digestive enzymes are shown in Table 4.

[0113] Table 4: Comparison of the inhibition rates of the compositions on digestive enzymes

[0114] As can be seen from the data in the table, the composition exhibits the best inhibition rates for pancreatic lipase, α-glucosidase, and cholesterol esterase. This is mainly due to the following synergistic mechanism: Component A (resistant starch), acting as a sustained-release carbon source, forms a viscous hydration layer in the small intestine, delaying substrate-enzyme contact and providing a longer-lasting window of action for the active ingredients in component C. The short-chain fatty acids and organic acids produced by the metabolism of component B (probiotics) can regulate the pH of the intestinal microenvironment, enhancing the competitive inhibitory effect of active ingredients such as flavonoids and alkaloids from food-derived medicinal sources in component C on digestive enzymes. Multiple active ingredients in component C (food-derived medicinal sources + prebiotics) (such as lotus leaf alkaloids, hawthorn flavonoids, and chlorogenic acid) can simultaneously act on different binding sites of enzymes, forming multi-site inhibition. The presence of probiotics and resistant starch further optimizes the dissolution and bioavailability of these components. The technical significance of this synergistic effect lies in: overcoming the bottleneck of limited inhibitory efficiency of single components on metabolic enzymes, improving the blocking ability of carbohydrate, fat, and cholesterol absorption; providing enzymatic evidence for the efficacy of the composition in improving insulin resistance, regulating glucose and lipid metabolism, and reducing body fat percentage, and supporting multi-target precision intervention for metabolic syndrome.

[0115] Test Experiment 4 The water-holding capacity, swelling capacity, 1-hour viscosity (mPa·s), and viscosity retention (%) of the composition of Example 1, resistant starch, polydextrose, oat β-glucan, and inulin were tested. The test methods are as follows: Water-holding capacity (WHC): Accurately weigh 0.5 g (accurate to 0.001 g) of sample into a 50 mL centrifuge tube (m0), add 30 mL of deionized water (25±1℃), vortex for 30 s to fully disperse, let stand for 30 min (simulating the time of water absorption and expansion in the stomach), centrifuge at 3000 r / min for 15 min, discard the supernatant, invert the centrifuge tube to drain for 15 min, and weigh the mass of wet residue (m1).

[0116] Swelling (SW): Accurately weigh 0.5g of sample into a 10mL graduated cylinder, read the dry sample volume V0 (mL), add 5mL of deionized water (25±1℃), gently shake to mix, add 5mL of deionized water (25±1℃), gently shake to mix, and read the volume after swelling V1 (mL).

[0117] Viscosity (SW): Simulated gastric fluid: containing 0.2% NaCl and 0.32% pepsin (3000 U / mg), pH adjusted to 3.0 ± 0.1 with 0.1 mol / L HCl, and sterilized through a 0.22 μm filter membrane. Weigh 0.40 g of each sample (accurate to 0.001 g), place it in a 50 mL Erlenmeyer flask, add 20.0 mL of simulated gastric fluid preheated to 37 °C, vortex for 30 seconds (3000 rpm) to ensure no clumping, transfer the dispersion to the rheometer measuring cylinder, and start the program to automatically record the viscosity value.

[0118] The calculation formula is as follows:

[0119] The experimental results are shown in Table 5.

[0120] Table 5: Test results of water holding capacity, swelling capacity, and viscosity

[0121] As shown in the table above, the composition exhibits optimal water-holding capacity, swelling power, rapid (1-hour) viscosity, and viscosity retention. The water-holding capacity of the composition (12.5 ± 1.8 mL / g) is 4.5 times that of commercially available inulin, and the swelling power is increased by 3.4 times, confirming the successful construction of the stereogel network. The viscosity retention rate (72 ± 9%) is significantly higher than that of pure resistant starch (65 ± 8%), but lower than that of polydextrose (88 ± 6%), indicating that the composite system balances instantaneous satiety with long-lasting sustained release.

[0122] The different components of the prebiotics mentioned above play different roles, as detailed below: ① Physical satiety in the stomach: Resistant starch has a water-holding capacity of (8.5±1.2) mL / g, forming a high-viscosity gel in the stomach within 30 seconds, physically delaying gastric emptying by 54-60%; ② Viscosity barrier in the small intestine: Oat β-glucan forms a "viscous barrier layer" in the small intestine, with a viscosity retention rate of ≥55%, inhibiting fat absorption through physical encapsulation and promoting bile acid chelation; ③ Medium-speed fermentation in the mid-colon: Inulin continuously promotes the growth of anti-inflammatory strains such as Faecalibacterium prausnitzii; ④ Slow fermentation in the distal colon: Resistant dextrin continuously releases butyrate for 12-24 hours, repairing tight junction proteins in the intestinal epithelium; ⑤ Whole-intestinal sustained-release framework: The water-holding capacity and slow fermentation characteristics of polydextrose make it a backbone component for "slow energy release and maintenance of gut microbiota homeostasis," with a water-holding capacity retention rate of ≥60% over 180 min.

[0123] The prebiotic components in the composition can form a dual gradient system of "rapid satiety - viscosity maintenance - rapid fermentation - medium-speed fermentation - slow fermentation - long-term sustained release", ensuring that probiotics throughout the colon receive a continuous supply of nutrients, and avoiding the defects of "overlapping action sites and excessively short fermentation window" of single prebiotics.

[0124] Test Experiment 5 The study investigated the effects of interventions with resistant dextrin, xylooligosaccharides, inulin, oat β-glucan, polydextrose, and the composition of Example 1 on the content of short-chain fatty acids (SCFAs) in the feces of obese mice. Thirty-five obese model mice were divided into seven groups: a blank control group, a resistant dextrin group, a xylooligosaccharide group, an inulin group, an oat β-glucan group, a polydextrose group, and the composition group. The obese model mice were adult C57BL / 6J mice, with the smallest weighing over 42g and the largest weighing 50g.

[0125] Experimental Methods: Resistant dextrin, xylooligosaccharides, inulin, oat β-glucan, polydextrose, and the composition of Example 1 were all prepared into suspensions of equal concentration using sterile physiological saline (ensuring consistent prebiotic dosage). The control group was administered an equal volume of sterile physiological saline by gavage, while the other groups were administered 100 mg / kg body weight once daily by gavage for 8 consecutive weeks. Throughout the intervention, all mice were fed a standard high-fat diet with free access to food and water, and kept in a consistent environment (temperature 22-25℃, 12h light-dark cycle). At the end of the 8-week intervention, the mice were fasted for 12 hours (with free access to water). The mice were then placed individually in sterile metabolic cages, and fresh fecal samples were collected (within 1 hour), with at least 0.5 g collected from each mouse. The samples were aliquoted into sterile centrifuge tubes, rapidly frozen in liquid nitrogen, and then stored at -80℃ to prevent SCFA decomposition. Take 0.1g of frozen fecal sample, add 1mL of sterile ultrapure water, vortex for 1min to homogenize; centrifuge at 4℃ and 12000r / min for 15min, and take the supernatant; add an equal volume of chromatographic grade methanol (deproteinized), vortex again for 1min, and centrifuge at 4℃ and 12000r / min for 10min; filter the supernatant through a 0.22μm organic phase filter membrane to obtain the SCFA detection sample for later use.

[0126] High-performance liquid chromatography (HPLC) was used for detection, and the chromatographic conditions were consistent with those of the aforementioned in vitro experiments (C18 reversed-phase column, mobile phase 0.05 mol / L phosphoric acid aqueous solution: methanol = 95:5, flow rate 1.0 mL / min, column temperature 30℃, detection wavelength 210 nm). Standard curves were plotted using SCFA standards such as acetic acid, propionic acid, and butyric acid. The total SCFA and the content of monomeric SCFAs such as butyric acid, acetic acid, and propionic acid (μmol / g feces) were calculated based on the peak area of ​​the samples. The average value of each group of mice was taken, and the test results are shown in Table 6.

[0127] Table 6: Short-chain fatty acid content in obese mice after intervention with different prebiotics or combinations

[0128] Experiments showed that the total SCFA content in mouse feces of the composition sample of Example 1 reached 45.5±5.1 μmol / g, an increase of 122% compared with the control group. The feces of mice using the composition sample of Example 1 showed the highest contents of acetic acid, propionic acid, and butyric acid. The total SCFA content in the xylooligosaccharide group was 35.8±4.0 μmol / g, and inulin group was 36.7±4.1 μmol / g, both lower than that in the composition group. The composition sample of Example 1 significantly increased the total SCFA and butyric acid production in the intestine of animals, confirming the in vivo effectiveness of the gradient fermentation design.

[0129] Example 2 This embodiment describes a colon-targeted microecological regulation composition powder, suitable for individuals with comprehensive metabolic disorders. Its active ingredients are as follows: Component A: 65% wet-heat modified resistant starch (DP≥16, crystallinity≥35%); Component B: Encapsulated Lactobacillus rhamnosus (extrusion-gel method encapsulation, encapsulation rate 78%, 2-hour survival rate in simulated gastric juice 62%, 4-hour survival rate in simulated intestinal juice 52%, viable count ≥1.0×10⁻⁶). 9 (CFU / g); based on the dry weight of probiotics, component B accounts for 12%.

[0130] Component C: 3% fructooligosaccharides (DP2-8 content ≥82%, purity ≥86%), 4% oat β-glucan, 2.5% polydextrose, 1.5% carrageenan (prebiotic microencapsulation modification) + 12% yam powder (ultra-fine pulverization and cell wall breaking), a medicinal and edible homology composition.

[0131] The preparation method is the same as in Example 1. The total mixture is divided into 8g / strips, sealed and packaged to obtain the powder composition.

[0132] A human taste test was conducted on the product of Example 2: 1. Target audience requirements Inclusion criteria: Overweight / obese subjects with a BMI of 24.0-32.0 kg / m² and a waist circumference of ≥85cm for men or ≥80cm for women. Number of participants: 60 (30 in the experimental group and 30 in the placebo group) Age range: 20-60 years old 2. Dosage and method of consumption Directions for use: Take 10 grams twice daily. Timing of consumption: Take with warm water 30 minutes before breakfast and dinner. Consumption period: 8 weeks 3. Monitoring Indicators Key indicators: weight, waist circumference, BMI, body fat percentage Other indicators: satiety time, blood glucose, triglycerides, total cholesterol, high-density lipoprotein. Testing frequency: Once a week, comparing values ​​before and after the experiment. 4. Test Results 1) Main Indicators and Experimental Results Figs. 1-2 The changes in key monitoring indicators in the experimental group and the placebo group before and 8 weeks after taking the product are presented.

[0133] Trial data showed that after 8 weeks, the weight of the experimental group decreased from the baseline average (78.5±8.2kg) to 73.7±7.8kg, with an average weight loss of 4.8±1.2kg, which was better than the placebo group's 1.2±0.8kg, with a net difference of -3.6kg between the groups; the body fat percentage of the experimental group decreased from the baseline value of 34.2 to 31.8, a decrease of about 2.4 (the placebo group only decreased by 0.5), and the waist circumference decreased by 5.8±1.5cm (the placebo group -1.8±1.1cm), with the waist circumference reduction being greater than that of the placebo group.

[0134] 2) Satiety score assessment The satiety level of the product was assessed using a 7-point simulated rating scale. Satiety scores were assessed at 0, 30, 60, 90, 120, 150, and 180 minutes after consuming the test product. The rating scale ranged from -3 "very hungry" to +3 "unpleasantly full," with 0 indicating no noticeable feeling of satiety or hunger. The experimental results are shown in Table 7.

[0135] Table 7: Time-series changes in satiety scores

[0136] Table 7 shows the dynamic changes in postprandial satiety in the participants. It can be seen that after 8 weeks of intervention, the peak and duration of postprandial satiety with the composition of this invention both increased. Data from a 7-point scale confirm that after 8 weeks of intervention, the peak postprandial satiety with the composition of this invention increased by 37%, the duration increased by 65% ​​(66 minutes), and the total effect AUC increased by 83.9%. Furthermore, mild satiety was maintained at 180 minutes (+0.8 points), significantly better than the placebo (-0.3 points, in a state of hunger). No abnormal fluctuations were observed, demonstrating scientific validity and reproducibility, directly supporting the innovative point of the present invention: the synergistic effect of "physical satiety-microbial metabolism."

[0137] 3) Other indicators The participants underwent tests to assess changes in glucose and lipid metabolism, inflammatory markers, gut microbiota, and SCFA. The results are shown in Tables 8-9.

[0138] Table 8: Changes in Glucose and Lipid Metabolism and Inflammatory Indicators

[0139] Table 9: Changes in Gut Microbiota and SCFA

[0140] 4) Security assessment, see Table 10.

[0141] Table 10: Adverse event incidence (n=30)

[0142] Safety evaluation showed that all adverse events in the experimental group were mild gastrointestinal reactions (abdominal distension 13.3%, increased flatulence 6.7%, mild diarrhea 3.3%, constipation 3.3%), with a total incidence of 26.7%. Mild gastrointestinal reactions are normal physiological responses to prebiotics and do not pose a safety concern.

[0143] This invention is based on the synergistic theory of "carbon source sustained release - gut microbiota targeting - metabolic regulation." Through systematic in vitro experiments, animal model validation, and human trials, it has demonstrated the significant advantages of the composition in improving energy metabolism, optimizing gut microbiota structure, increasing SCFA production, regulating glucose and lipid metabolism, and maintaining immune balance. This technical solution addresses the shortcomings of existing products, such as single mechanism of action, low probiotic colonization rate, poor compliance, and easy rebound, providing an innovative and industrially scalable solution for nutritional intervention in metabolic syndrome.

[0144] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features. These modifications or substitutions, or combinations of technical features in the above embodiments that do not conflict with each other, can be made in accordance with the manner described in the embodiments. These modifications, substitutions or combinations do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A colon-targeted microecological regulation composition, characterized in that, Its active ingredients are compounded from 5-95% component A, 1-15% component B, and 4-94% component C by weight percentage. Component A is resistant starch with a degree of polymerization (DP) ≥ 15 and a crystallinity ≥ 35%. Component B is a probiotic, encapsulated using a complex coagulation method or an extrusion-gel method, with an encapsulation rate ≥75%. Its tolerance to overdigestion meets the following requirements: survival rate ≥60% after treatment in simulated gastric juice for 2 hours and survival rate ≥50% after treatment in simulated intestinal juice for 4 hours. Component C contains functional nutritional excipients; the functional nutritional excipients include prebiotics and food-medicine homologous compositions; the prebiotics include fast-fermenting prebiotics, medium-fermenting prebiotics, slow-fermenting prebiotics, and non-fermenting water-holding and swelling components.

2. The colon-targeted microecological regulation composition according to claim 1, characterized in that, The fast-fermenting prebiotic is selected from at least one of xylooligosaccharides, fructooligosaccharides, galactooligosaccharides, stachyose, and cottonseed oligosaccharides; the medium-fermenting prebiotic is selected from at least one of inulin, oat β-glucan, pectin, and gum arabic; the slow-fermenting prebiotic is selected from at least one of resistant dextrin, polydextrose, psyllium husk, and cellulose; and the non-fermenting water-holding swelling component is selected from at least one of konjac flour, carrageenan, xanthan gum, and guar gum.

3. The colon-targeted microecological regulation composition according to claim 2, characterized in that, The mass ratio of fast-fermenting, medium-fermenting, and slow-fermenting prebiotics to non-fermenting water-holding and swelling components in component C is (1.0-3.5):(1.0-4.5):(1.0-3.0):(1.0-2.0); preferably 2.0:2.0:2.0:1.

0.

4. The colon-targeted microecological regulation composition according to claim 1, 2, or 3, characterized in that, The medicinal and edible homology composition contains one or more of the following: spleen-strengthening and dampness-eliminating medicinal and edible homology substances, heat-clearing and dampness-resolving medicinal and edible homology substances, digestion-aiding and food-resolving medicinal and edible homology substances, bowel-moistening and laxative medicinal and edible homology substances, phlegm-resolving and dampness-eliminating medicinal and edible homology substances, qi-tonifying and yin-nourishing medicinal and edible homology substances, and other medicinal and edible homology substances. The spleen-strengthening and dampness-eliminating medicinal and edible substances are selected from at least one of Poria cocos, Coix seed, Dioscorea opposita, white hyacinth bean, and red adzuki bean; the heat-clearing and dampness-resolving medicinal and edible substances are selected from at least one of lotus leaf, cassia seed, chrysanthemum, honeysuckle, and gardenia; the digestive and food-resolving medicinal and edible substances are selected from at least one of hawthorn, radish seed, malt, and chicken gizzard lining; the bowel-moistening and laxative medicinal and edible substances are selected from at least one of hemp seed, Prunus japonica seed, mulberry, and black sesame; the phlegm-resolving and dampness-eliminating medicinal and edible substances are selected from at least one of tangerine peel, citron, perilla, ginger, and cinnamon; the qi-tonifying and yin-nourishing medicinal and edible substances are selected from at least one of Polygonatum sibiricum, Polygonatum odoratum, wolfberry, lily, and sea buckthorn; and other medicinal and edible substances are selected from at least one of Sophora japonica flower, dandelion, and agastache rugosa.

5. The colon-targeted microecological regulation composition according to claim 1, characterized in that, It also includes pharmaceutical excipients, which include binders, lubricants and disintegrants; the binders are at least one of sorbitol, maltodextrin, microcrystalline cellulose, lactose, compressible starch, polyethylene oxide and povidone; the lubricants are at least one of magnesium stearate, stearic acid, calcium stearate and silicon dioxide; and the disintegrants are at least one of sodium carboxymethyl starch and dry starch.

6. The colon-targeted microecological regulation composition according to claim 1, characterized in that, The bioavailability of the medicinal and edible substances in component C is improved by one or more of the following methods: ultrafine pulverization and cell wall breaking, low-temperature extraction, supercritical CO2 extraction, and microwave-assisted extraction; the prebiotics are modified by one or more of the following methods: microencapsulation, molecular weight classification, oxidative cross-linking, and mineral chelation.

7. The colon-targeted microecological regulation composition according to claim 1, characterized in that, The resistant starch of component A is a polysaccharide and its derivatives composed of D-glucose units linked by α-1,4 and / or α-1,6 glycosidic bonds, and its resistance is enhanced by wet heat modification; the digestibility of component A is ≤30% based on the small intestinal digestibility determined by the ISO 26642:2010 method. Component B is one or more strains of Bifidobacterium, Lactobacillus, and Clostridium butyricum.

8. The use of the colon-targeted microecological regulation composition according to any one of claims 1-7 in the preparation of functional foods for the intervention of metabolic syndrome.

9. The application according to claim 8, characterized in that, The functional foods described herein have one or more of the following effects: improving insulin resistance, optimizing gut microbiota structure, increasing the production of short-chain fatty acids in the gut, regulating glucose and lipid metabolism, reducing body fat percentage, shrinking waist circumference, repairing the intestinal mucosal barrier, and prolonging satiety time.

10. The application according to claim 8, characterized in that, For individuals with hyperglycemia, the effective components of the colon-targeted microecological regulation composition include component A (80-95%), component B (1-10%), and component C (4-10%). For individuals with comprehensive metabolic disorders, the effective components of the colon-targeted microecological regulation composition include component A (54-72%), component B (6-15%), and component C (22-35%).

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