A composition comprising mouse-derived Akkermansia muciniphila 139 strain and dietary fiber combination components and use thereof

Abstract

The present invention discloses a composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein the ratio of the number of viable bacteria of the rat-derived Akkermansia muciniphila 139 strain to the total dietary fiber content in the dietary fiber combination component is 100×10 8 cfu:1g~400×10 8 cfu: 1g. The composition comprising the mouse-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component can increase the ability of the whole intestine to produce short-chain fatty acids, especially the content of butyrate, thereby stimulating intestinal L cells to efficiently produce GLP-1 and PYY, and improving various metabolic diseases caused by such endocrine disorders.

Description

Technical Field

[0001] The present invention belongs to the technical fields of compositions, microorganisms, metabolic disease treatment and nutrition, and in particular to the technology of intestinal health and promoting the production of short-chain fatty acids by probiotics in the intestine. Short-chain fatty acids have important specific effects in the treatment of metabolic diseases such as diabetes, and specifically to a composition comprising a mouse-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, and use thereof. Background Art

[0002] The human intestine is a complex and delicate ecosystem, which is composed of trillions of microorganisms, which constitute the intestinal flora. Among these microorganisms, probiotics play a vital role. The probiotics in humans and animals are mainly lactic acid bacteria, bifidobacteria, Lactobacillus acidophilus, etc. The presence of probiotics is essential for maintaining the stability of the intestinal environment, and they promote the health of the host through various mechanisms. Probiotics can help digestion. They can break down complex carbohydrates in food and produce short-chain fatty acids (SCFAs), such as acetic acid, propionic acid and butyric acid. These short-chain fatty acids play multiple roles in gastrointestinal health, from maintaining the intestinal barrier to providing energy, to immune regulation and anti-inflammatory effects. They are an indispensable part of intestinal health. They are not only an important source of energy for intestinal cells, but also have a positive effect on regulating blood sugar and cholesterol levels. In principle, short-chain fatty acids can improve various metabolic diseases caused by endocrine disorders such as GLP-1 and PYY, such as diabetes and prediabetes, overweight and obesity, polycystic ovary syndrome, etc. For example, short-chain fatty acids can selectively improve intestinal flora and thus slow down the course of type 2 diabetes. They improve glucose homeostasis by inducing the production of glucagon-like peptide-1 (GLP-1) and PYY in the intestine, thereby stimulating insulin secretion. Short-chain fatty acids play an important specific role in the treatment of diabetes.

[0003] Dietary fiber is a type of carbohydrate that is not easily digested by the human body and is mainly found in plant foods. Dietary fiber can serve as "food" for probiotics, promoting their growth and activity, thereby helping to maintain intestinal health. Dietary fiber can stimulate the proliferation of probiotics, improve the balance of intestinal flora, enhance intestinal barrier function, inhibit the growth of harmful bacteria, and regulate the immune system and blood sugar levels.

[0004] In practical applications, the combined use of probiotics and dietary fiber can complement each other and jointly promote intestinal health. Probiotics mainly metabolize dietary fiber as food to produce target products that are beneficial to human health, among which short-chain fatty acids are the most important metabolites. Only probiotics with genes that produce short-chain fatty acids can produce short-chain fatty acids. At the same time, giving intestinal probiotics suitable food can be more conducive to the production and accumulation of more short-chain fatty acids by intestinal probiotics. However, it should be noted that not all probiotics and dietary fiber have the same effects. Their types, dosages, ratios, etc. will affect the final effect.

[0005] Patent document CN111321089B discloses a mouse-derived Akkermansia muciniphila 139 strain and its use, which has the potential to produce more short-chain fatty acids by in vitro fermentation to maintain the intestinal health of the host. Therefore, developing a composition comprising a mouse-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, which can produce more short-chain fatty acids in the intestine, has important application value. Summary of the invention

[0006] The technical problem to be solved by the present invention is to provide a composition comprising a mouse-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component and a use thereof.

[0007] The mouse-derived Akkermansia muciniphila 139 strain (i.e. the strain disclosed in patent document CN111321089B, also referred to as "mouse-derived Akkermansia 139 strain" or mouse-derived Akkermansia (Akkermansia muciniphila) 139 strain) is deposited in the General Microbiology Center of China Microorganism Culture Collection (CGMCC), with the address at No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing (postal code 100101), the deposit number is CGMCC NO.16758, the deposit date is November 21, 2018, and the classification name is Akkermansia muciniphila.

[0008] Akkermansia muciniphila 139 strain has the following biological characteristics:

[0009] Strain morphology: The bacterial body size is about 0.9×0.5μm, with a smooth surface, oval shape, and no flagella.

[0010] The specific technical solution adopted by the present invention is as follows:

[0011] The present invention provides a composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein the ratio of the number of viable bacteria of the rat-derived Akkermansia muciniphila 139 strain to the total dietary fiber content in the dietary fiber combination component is 100×10 8 cfu:1g~400×10 8 cfu:1g.

[0012] The dietary fiber combination ingredients include insoluble dietary fiber and soluble dietary fiber, which together constitute the dietary fiber in the dietary fiber combination ingredients.

[0013] Furthermore, the mass ratio of the insoluble dietary fiber to the soluble dietary fiber is 9:1 to 10:1.

[0014] Preferably, the mass ratio of the insoluble dietary fiber to the soluble dietary fiber is 2:1.

[0015] Preferably, the mass ratio of the insoluble dietary fiber to the soluble dietary fiber is 9.5:1.

[0016] In some specific embodiments, the ratio of the viable count of the mouse-derived Akkermansia muciniphila 139 strain to the total dietary fiber content in the dietary fiber combination component is 180×10 8 cfu:1g~220 ×10 8 cfu:1g.

[0017] The ratio of the viable bacterial count of the mouse-derived Akkermansia muciniphila 139 strain to the total dietary fiber content in the dietary fiber combination component is 180×10 8 cfu:1g~220 ×10 8 cfu: 1g, more short-chain fatty acids are produced; at other ratios, the output of short-chain fatty acids is not as good as the output of short-chain fatty acids under this ratio, but generally higher than the output of short-chain fatty acids under this ratio of other strains such as Bifidobacterium animalis, Lactobacillus acidophilus, Lactobacillus rhamnosus, etc. The short-chain fatty acids include acetic acid, propionic acid, and butyric acid.

[0018] In some specific embodiments, the dietary fiber combination ingredient comprises cereals and tubers and prebiotics.

[0019] Cereals and tubers, cereals refer to the grains of cereals, and the raw materials are taken from the whole grain or the cortex of cereals; tubers, also known as root crops, refer to terrestrial crops with edible roots or tubers, and the raw materials are taken from the dietary fiber part of tuber starch or the whole tuber dry powder. Prebiotics are industrialized oligosaccharides or soluble polysaccharides.

[0020] The dietary fiber of cereals and tubers is mainly insoluble dietary fiber, while the dietary fiber of prebiotics is mainly soluble dietary fiber, which has a simple structure and small molecular weight.

[0021] In some specific embodiments, the cereal plant is selected from one or more of wheat, oats, highland barley, rice, buckwheat, coix seed, sweet buckwheat, rye, rye bran, yam, kudzu root, potato, sweet potato, corn bran, millet, and sorghum.

[0022] In some specific embodiments, the cereal and tuber plants are selected from one or more of wheat bran, oat bran, highland barley bran, rice bran, buckwheat bran, coix seed powder, sweet buckwheat powder, rye flour, rye bran powder, yam powder, kudzu root powder, potato fiber powder, sweet potato fiber powder, corn bran powder, millet flour, and sorghum flour.

[0023] In one or more embodiments of the present invention, by weight percentage, the dietary fiber contained in wheat bran accounts for 50%; the dietary fiber contained in oat bran accounts for 35%; the dietary fiber contained in highland barley bran accounts for 30%; the dietary fiber contained in rice bran accounts for 40%; the dietary fiber contained in tartary buckwheat bran accounts for 40%; the dietary fiber contained in coix seed powder accounts for 8%; the dietary fiber contained in sweet buckwheat powder accounts for 40%; the dietary fiber contained in rye flour accounts for 15%; the dietary fiber contained in rye bran powder accounts for 50%; the dietary fiber contained in yam powder accounts for 8%; the dietary fiber contained in kudzu root powder accounts for 5%; the dietary fiber contained in potato fiber powder accounts for 70%; the dietary fiber contained in sweet potato fiber powder accounts for 70%; the dietary fiber contained in corn bran powder accounts for 30%; the dietary fiber contained in corn flour accounts for 5%; the dietary fiber contained in sorghum flour accounts for 7%.

[0024] In some specific embodiments, the prebiotic is selected from one or more of resistant dextrin, inulin, fructooligosaccharides, xylo-oligosaccharides, and polydextrose.

[0025] In one or more embodiments of the present invention, by weight percentage, the dietary fiber contained in resistant dextrin accounts for 85%; the dietary fiber contained in inulin accounts for 88%; the dietary fiber contained in oligofructose accounts for 95%; the dietary fiber contained in oligoxylose accounts for 95%; and the dietary fiber contained in polydextrose accounts for 90%.

[0026] In some specific embodiments, the cereal and tuber plants are selected from 0-23% wheat bran, 0-18% oat bran, 0-22% highland barley bran, 0-30% rice bran, 0-18% tartary buckwheat bran, 0-9% coix seed powder, 0-18% sweet buckwheat powder, 0-14% rye flour, 0-20% rye bran powder, 0-14% yam powder, 0-1 6% kudzu root powder, 0-30% potato fiber powder, 0-29% sweet potato fiber powder, 0-15% corn bran powder, 0-14% corn flour, 0-11% sorghum flour or one or more thereof; prebiotics are selected from one or more of 0-12% resistant dextrin, 0-13% inulin, 0-16% oligofructose, 0-10% oligoxylose, and 0-15% polydextrose.

[0027] Use of the composition comprising the mouse-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component as described above in promoting the production of short-chain fatty acids in the intestine.

[0028] The short-chain fatty acids produced in the intestine are mainly acetic acid, propionic acid and butyric acid.

[0029] The composition comprising the mouse-derived Akkermansia muciniphila 139 strain and dietary fiber combination components is used in promoting intestinal butyrate production.

[0030] Due to the change in lifestyle, the intestinal microecology has changed in a short period of time. The probiotics that have long been rooted in the intestines and produce short-chain fatty acids have become weak bacteria in the intestines. In addition, the dietary fiber for long-term domestication of such probiotics is seriously insufficient, resulting in a serious shortage of short-chain fatty acids, which are important target metabolites of intestinal microecology in the short term. Short-chain fatty acids are important target metabolites for intestinal health. The lack of short-chain fatty acids, especially butyrate, has brought many endocrine and metabolic health problems to humans.

[0031] Use of the composition comprising the mouse-derived Akkermansia muciniphila 139 strain and dietary fiber combination components as described above in the preparation of a drug for controlling postprandial blood sugar and adjusting the intestinal flora structure.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] The composition comprising the mouse Akkermansia muciniphila 139 strain and the dietary fiber combination component can increase the ability of the whole intestine to produce short-chain fatty acids, especially the content of butyrate, thereby stimulating intestinal L cells to efficiently produce GLP-1 and PYY, and improving various metabolic diseases caused by such endocrine disorders, such as diabetes and prediabetes, overweight and obesity, polycystic ovary syndrome, etc. The ratio of the number of viable bacteria of the mouse Akkermansia muciniphila 139 strain to the total dietary fiber content in the dietary fiber combination component is 100×10 8 cfu:1g~400×10 8 cfu: 1g or the mass ratio of insoluble dietary fiber to soluble dietary fiber is 1:1-4:1 or 9:1-10:1, the composition comprising the mouse Akkermansia muciniphila 139 strain and the dietary fiber combination component can produce significantly more short-chain fatty acids, and the ratio of the viable bacterial count of the mouse Akkermansia muciniphila 139 strain to the total dietary fiber content in the dietary fiber combination component is 180×10 8 cfu:1g~220 ×10 8 When cfu:1g, the effect of producing short-chain fatty acids is more significant.

[0034] The concept and technical effects of the present invention will be further described below in conjunction with the accompanying drawings to fully understand the purpose, features and effects of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 It is a scatter plot of the amounts of short-chain fatty acids in Examples 1 to 23. DETAILED DESCRIPTION

[0036] In order to make the technical means, creative features, objectives and effects of the invention easier to understand, the invention is further described below. However, the invention is not limited to the following implementation cases.

[0037] It should be noted that the contents illustrated in the drawings in this specification are only used to match the contents disclosed in the specification so as to facilitate understanding and reading by persons familiar with this technology, and are not used to limit the conditions under which the present invention can be implemented. Therefore, they have no substantive technical significance. Any non-creative adjustments should still fall within the scope of the technical contents disclosed in the present invention without affecting the effects and purposes that can be achieved by the present invention.

[0038] The rat-derived Akkermansia muciniphila 139 strain (also known as "rat-derived Akkermansia 139 strain" or rat-derived Akkermansia (Akkermansia muciniphila) 139 strain) is deposited in the General Microbiology Center of China Microorganism Culture Collection (CGMCC), located at No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing (postal code 100101), with the deposit number CGMCC NO.16758, the deposit date being November 21, 2018, and the classification name being Akkermansia muciniphila.

[0039] Animal Bifidobacterium was purchased from Chr. Hansen (Beijing) Trading Co., Ltd. The specific product name is Probio-Tec®BB-12® Blend-30 IF.

[0040] Lactobacillus acidophilus was purchased from Chr. Hansen (Beijing) Trading Co., Ltd. The specific product name is Probio-Tec® LA-5® Blend-30.

[0041] Lactobacillus rhamnosus was purchased from Chr. Hansen (Beijing) Trading Co., Ltd. The specific product name is Probio-Tec®LGG® Blend-30.

[0042] The in vitro fermentation model simulating intestinal flora was based on the literature De Paepe K, Verspreet J, Rezaei MN, et al. Modification of wheat bran particle size and tissue compositionaffects colonisation and metabolism by human faecal microbiota. Food Funct.2019; 10(1): 379-396. doi: 10.1039 / c8fo01272e. The dietary fiber combination components were first digested to remove macronutrients such as protein, starch and fat, and the substrate dietary fiber for intestinal flora and probiotics fermentation was retained. The dietary fiber substrate, fecal suspension mother liquor and probiotic powder used for fermentation were prepared separately, and the dietary fiber substrate and fecal suspension mother liquor were transferred to the anaerobic workstation, mixed evenly, and the intestinal flora fermented the substrate under suitable conditions. After the fermentation was completed, the samples were taken out, and the samples were processed and short-chain fatty acids were determined by gas chromatography and 16S sequencing.

[0043] The composition comprising Akkermansia muciniphila 139 strain of mouse origin and a dietary fiber combination component is prepared by the following method:

[0044] Preparation of dietary fiber substrate: Cereal and tuber plants were pre-treated with simulated digestion according to the following process: 30 g of sample was evenly dissolved in 300 mL of simulated gastric fluid (simulated gastric fluid: 0.9 mmol / L H3PO4, 3 mmol / L CaCl2, 0.1 mol / L HCl, 0.15 mol / L NaCl, 16 mmol / L KCl, pH 2.5), 1.875 g of pepsin was added, and the mixture was shaken in a 37 ℃ water bath (170 r / min) to simulate gastric digestion for 60 min; then the pH value of the reactant was adjusted to 6.5 with 300 mL of simulated intestinal fluid preheated to 37 ℃ (simulated intestinal fluid: 0.7 mmol / L Na2HPO4, 0.49 mmol / L MgCl2, 4.56 mmol / L KCl, 1.5 mmol / L NaH2PO4, 54.46 mmol / L NaCl, 80.36 mmol / L NaHCO3, pH 2.5). 7), add 93.75 mg porcine trypsin, 6.6 g porcine pancreatic amylase and 120 mg amyloglucosidase, shake in a water bath at 37 °C for 240 min (170 r / min), stop the reaction in a water bath at 95 °C for 5 min, collect soluble and insoluble dietary fiber by 4 times the volume of anhydrous ethanol at 4 °C for 2 h, centrifuge at 4000 rpm for 10 min, collect the residue, centrifuge at 3000 rpm for 10 min with acetone, dry in an oven at 45 °C for 6 h, then crush and calculate the yield (%). The digestion products of cereals and tubers after simulated digestion were added to the final model by multiplying the added mass (g) by the yield (%), and mixed with prebiotics to obtain the dietary fiber substrate required for fermentation.

[0045] Preparation of probiotic powder: A single colony of Akkermansia muciniphila 139 was inoculated into 2 ml of Brain Heart Infusion (BHI) broth containing 0.4% (w / v) mucin, and cultured at 37°C in an anaerobic environment for 24 hours. Then, it was transferred to 10 ml of the same culture medium at a ratio of 3% (v / v), and cultured at 37°C in an anaerobic environment for 24 hours. Finally, it was transferred to 200 ml of the culture system at a ratio of 3% (v / v), and cultured at 37°C in an anaerobic environment for 24 hours. The cultured bacterial solution was centrifuged at 8000g for 20 min, the supernatant was removed, 5 ml of PBS was added, and the solution was centrifuged at 8000g for 20 min again, and the supernatant was removed. The bacteria were resuspended in 2 ml of anaerobic PBS, mixed, and then plated for gradient dilution counting. After that, the solution was freeze-dried in a vacuum freeze dryer for 24 h, the freeze-dried powder was weighed, and the number of cfu per gram of powder was calculated.

[0046] Fecal suspension preparation: Take out the collected fecal sample, weigh 6g, put it into the prepared 50ml centrifuge tube, immediately add 30ml of phosphate buffer, shake and mix thoroughly; multiple tubes can be prepared repeatedly. Filter the mixed fecal suspension into a 100ml beaker with double-layer medical gauze, and use a glass rod to gently stir or press the gauze to help filter; filter the filtered liquid again with double-layer medical gauze; pour the filtered fecal suspension into a new 500ml blue-mouth bottle and mix well.

[0047] In the final model, dietary fiber substrate and probiotics were added according to the test ratio, and the fecal suspension concentration was 5% (w / v).

[0048] In terms of weight percentage, wheat bran contains 50% dietary fiber; oat bran contains 35% dietary fiber; barley bran contains 30% dietary fiber; rice bran contains 40% dietary fiber; buckwheat bran contains 40% dietary fiber; coix seed powder contains 8% dietary fiber; sweet buckwheat powder contains 40% dietary fiber; rye flour contains 15% dietary fiber; rye bran powder contains 50% dietary fiber; yam powder contains 8% dietary fiber; kudzu root powder contains 5% dietary fiber; potato fiber powder contains 70% dietary fiber; sweet potato fiber powder contains 70% dietary fiber; corn bran powder contains 30% dietary fiber; corn flour contains 5% dietary fiber; sorghum flour contains 7% dietary fiber.

[0049] In terms of weight percentage, resistant dextrin contains 85% dietary fiber; inulin contains 88% dietary fiber; oligofructose contains 95% dietary fiber; oligoxylose contains 95% dietary fiber; and polydextrose contains 90% dietary fiber.

[0050] Comparative Example 1

[0051] In a blank experiment, the composition without the mouse-derived Akkermansia muciniphila 139 strain and the dietary fiber combination components was tested by an in vitro fermentation model simulating intestinal flora, and the short-chain fatty acid content was 1572 μg / ml and the butyric acid content was 396 μg / ml.

[0052] Comparative Example 2

[0053] Only the mouse-derived Akkermansia muciniphila 139 strain was used. 1g of probiotics contained 50 billion mouse-derived Akkermansia muciniphila 139 bacteria, and was formulated to contain 0.01g / ml mouse-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria was 5×10 8 cfu / ml) solution.

[0054] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 1.6×10 11 cfu / ml, the content of short-chain fatty acids was 2274μg / ml, and the content of butyric acid was 682μg / ml.

[0055] Comparative Example 3

[0056] The dietary fiber combination component alone is prepared into a solution containing 0.05 g / ml of the dietary fiber combination component.

[0057] Calculated in percentage by weight, the dietary fiber composition is as follows: 86% cereals and tubers, 14% prebiotics; the specific ingredients are 23% wheat bran, 4% barley bran, 22% rice bran, 5% buckwheat bran, 7% rye bran powder, 3% kudzu root powder, 15% potato fiber powder, 3% corn bran powder, 4% sorghum powder, 2% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 2% polydextrose.

[0058] The dietary fiber content of cereals and tubers in this dietary fiber combination is 39%, and the dietary fiber content of prebiotics is 13%, the ratio of the two is 3:1, and the total dietary fiber content of the two is 52%.

[0059] Through the in vitro fermentation model test simulating intestinal flora, the short-chain fatty acid content was 3069μg / ml and the butyric acid content was 847μg / ml. Example 1

[0060] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.01 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0061] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0062] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0063] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 195×10 8 cfu / g.

[0064] Through the in vitro fermentation model test simulating intestinal flora, the 16S sequencing of the mouse Akkermansia muciniphila139 strain was 1.2×10 12 cfu / ml, the short-chain fatty acid content was 9746μg / ml, and the butyric acid content was 2871μg / ml. Example 2

[0065] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.01 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0066] Calculated in percentage by weight, the dietary fiber composition is as follows: 84% cereals and tubers, 16% prebiotics; the specific ingredients are 21% wheat bran, 9% oat bran, 13% highland barley bran, 9% buckwheat bran, 5% coix seed powder, 4% rye flour, 4% yam powder, 5% kudzu root powder, 10% sweet potato fiber powder, 4% sorghum flour, 2% inulin, 5% oligofructose, 3% oligoxylose, and 6% polydextrose.

[0067] The dietary fiber content of cereals and tubers in the dietary fiber combination is 30%, and the dietary fiber content of prebiotics is 15%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 45%.

[0068] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 223×10 8 cfu / g.

[0069] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 7.7×10 11cfu / ml, the short-chain fatty acid content was 8473μg / ml, and the butyric acid content was 2262μg / ml. Example 3

[0070] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.01 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0071] Calculated by weight percentage, the dietary fiber composition is as follows: 80% cereals and tubers, 20% prebiotics; the specific ingredients are 11% wheat bran, 15% oat bran, 5% highland barley bran, 8% sweet buckwheat bran powder, 7% rye bran powder, 14% potato fiber powder, 7% sweet potato fiber powder, 7% corn bran powder, 6% corn flour, 2% resistant dextrin, 4% inulin, 5% oligofructose, 5% oligoxylo-oligosaccharide and 4% polydextrose.

[0072] The dietary fiber content of cereals and tubers in this dietary fiber combination is 36%, and the dietary fiber content of prebiotics is 18%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 54%.

[0073] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 184×10 8 cfu / g.

[0074] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 1.0×10 12 cfu / ml, the short-chain fatty acid content was 9246μg / ml, and the butyric acid content was 2562μg / ml. Example 4

[0075] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.01 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 5×10 8cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0076] Calculated by weight percentage, the dietary fiber composition is as follows: 72% cereals and tubers, 28% prebiotics; the specific ingredients are 7% wheat bran, 8% barley bran, 13% rice bran, 6% buckwheat bran, 8% rye flour, 5% yam flour, 10% potato fiber powder, 10% corn bran powder, 5% corn flour, 6% resistant dextrin, 8% inulin, 9% xylo-oligosaccharides, and 5% polydextrose.

[0077] The dietary fiber content of cereals and tubers in the dietary fiber combination is 25%, and the dietary fiber content of prebiotics is 25%, the ratio of the two is 1:1, and the total dietary fiber content of the two is 51%.

[0078] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 198×10 8 cfu / g.

[0079] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 6.2×10 11 cfu / ml, the short-chain fatty acid content was 7533μg / ml, and the butyric acid content was 1861μg / ml. Example 5

[0080] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.01 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0081] Calculated in percentage by weight, the dietary fiber composition is as follows: 89% cereals and tubers, 11% prebiotics; the specific ingredients are 16% wheat bran, 4% oat bran, 18% rice bran, 4% coix seed powder, 6% sweet buckwheat bran powder, 13% rye bran powder, 13% potato fiber powder, 6% sweet potato fiber powder, 4% corn flour, 5% sorghum flour, 3% resistant dextrin, 1% inulin, 2% oligofructose, and 5% polydextrose.

[0082] The dietary fiber content of cereals and tubers in the dietary fiber combination is 409%, and the dietary fiber content of prebiotics is 10%, the ratio of the two is 4:1, and the total dietary fiber content of the two is 50%.

[0083] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rat to total dietary fiber content was 202×10 8 cfu / g.

[0084] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 8.1×10 11 cfu / ml, the short-chain fatty acid content was 8763μg / ml, and the butyric acid content was 2382μg / ml. Example 6

[0085] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.01 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0086] Calculated in percentage by weight, the dietary fiber composition is as follows: 86% cereals and tubers, 14% prebiotics; the specific ingredients are 23% wheat bran, 4% barley bran, 22% rice bran, 5% buckwheat bran, 7% rye bran powder, 3% kudzu root powder, 15% potato fiber powder, 3% corn bran powder, 4% sorghum powder, 2% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 2% polydextrose.

[0087] The dietary fiber content of cereals and tubers in this dietary fiber combination is 39%, and the dietary fiber content of prebiotics is 13%, the ratio of the two is 3:1, and the total dietary fiber content of the two is 52%.

[0088] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 194×10 8 cfu / g.

[0089] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 8.5×10 11cfu / ml, the short-chain fatty acid content was 8835μg / ml, and the butyric acid content was 2425μg / ml. Example 7

[0090] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.025 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 12.5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0091] Calculated in percentage by weight, the dietary fiber composition is as follows: 86% cereals and tubers, 14% prebiotics; the specific ingredients are 23% wheat bran, 4% barley bran, 22% rice bran, 5% buckwheat bran, 7% rye bran powder, 3% kudzu root powder, 15% potato fiber powder, 3% corn bran powder, 4% sorghum powder, 2% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 2% polydextrose.

[0092] The dietary fiber content of cereals and tubers in this dietary fiber combination is 39%, and the dietary fiber content of prebiotics is 13%, the ratio of the two is 3:1, and the total dietary fiber content of the two is 52%.

[0093] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 484×10 8 cfu / g.

[0094] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 3.3×10 12 cfu / ml, the short-chain fatty acid content was 5975μg / ml, and the butyric acid content was 1923μg / ml. Example 8

[0095] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.005 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 2.5×10 8cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0096] Calculated in percentage by weight, the dietary fiber composition is as follows: 86% cereals and tubers, 14% prebiotics; the specific ingredients are 23% wheat bran, 4% barley bran, 22% rice bran, 5% buckwheat bran, 7% rye bran powder, 3% kudzu root powder, 15% potato fiber powder, 3% corn bran powder, 4% sorghum powder, 2% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 2% polydextrose.

[0097] The dietary fiber content of cereals and tubers in this dietary fiber combination is 39%, and the dietary fiber content of prebiotics is 13%, the ratio of the two is 3:1, and the total dietary fiber content of the two is 52%.

[0098] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rat to total dietary fiber content was 97×10 8 cfu / g.

[0099] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 4.5×10 11 cfu / ml, the short-chain fatty acid content was 6341μg / ml, and the butyric acid content was 1764μg / ml. Example 9

[0100] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.01 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0101] Calculated in percentage by weight, the dietary fiber composition is as follows: 89% cereals and tubers, 11% prebiotics; the specific ingredients are 7% wheat bran, 5% oat bran, 4% barley bran, 17% buckwheat bran, 14% rye flour, 16% kudzu root flour, 4% potato fiber powder, 14% corn flour, 8% sorghum flour, 2% resistant dextrin, 4% fructooligosaccharides, 2% xylo-oligosaccharides, and 3% polydextrose.

[0102] The dietary fiber content of cereals and tubers in the dietary fiber combination is 20%, and the dietary fiber content of prebiotics is 10%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 30%.

[0103] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 330×10 8 cfu / g.

[0104] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 2.5×10 11 cfu / ml, the short-chain fatty acid content was 4427μg / ml, and the butyric acid content was 1251μg / ml. Example 10

[0105] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.01 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0106] Calculated by weight percentage, the dietary fiber composition is as follows: 61% cereals and tubers, 39% prebiotics; the specific ingredients are 5% wheat bran, 4% oat bran, 3% highland barley bran, 8% sweet buckwheat bran powder, 20% potato fiber powder, 17% sweet potato fiber powder, 4% corn bran powder, 9% resistant dextrin, 13% inulin, 10% xylo-oligosaccharides, and 7% polydextrose.

[0107] The dietary fiber content of cereals and tubers in the dietary fiber combination is 35%, and the dietary fiber content of prebiotics is 35%, the ratio of the two is 1:1, and the total dietary fiber content of the two is 70%.

[0108] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rat to total dietary fiber content was 143×10 8 cfu / g.

[0109] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 4.5×10 11cfu / ml, the short-chain fatty acid content was 4949μg / ml, and the butyric acid content was 1477μg / ml. Embodiment 11

[0110] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.01 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0111] Calculated in percentage by weight, the dietary fiber composition is as follows: 57% cereals and tubers, 43% prebiotics; the specific ingredients are 4% wheat bran, 4% barley bran, 6% rice bran, 8% sweet buckwheat bran powder, 5% rye flour, 10% yam powder, 6% kudzu root powder, 6% corn bran powder, 8% corn flour, 12% resistant dextrin, 5% inulin, 16% oligofructose, and 10% xylo-oligosaccharide.

[0112] The dietary fiber content of cereals and tubers in the dietary fiber combination is 13%, and the dietary fiber content of prebiotics is 39%, the ratio of the two is 0.33:1, and the total dietary fiber content of the two is 52%.

[0113] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 192×10 8 cfu / g.

[0114] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 1.9×10 11 cfu / ml, the short-chain fatty acid content was 3995μg / ml, and the butyric acid content was 1201μg / ml. Example 12

[0115] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.01 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0116] Calculated in percentage by weight, the dietary fiber composition is as follows: 91% cereals and tubers, 9% prebiotics; the specific ingredients are 15% wheat bran, 8% oat bran, 6% rice bran, 5% coix seed powder, 13% rye flour, 4% yam powder, 12% potato fiber powder, 20% sweet potato fiber powder, 8% corn bran powder, 2% resistant dextrin, 2% inulin, 2% xylo-oligosaccharides, and 3% polydextrose.

[0117] The dietary fiber content of cereals and tubers in the dietary fiber combination is 40%, and the dietary fiber content of prebiotics is 8.1%. The ratio of the two is 5:1, and the total dietary fiber content of the two is 48%.

[0118] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 207×10 8 cfu / g.

[0119] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 4.9×10 11 cfu / ml, the short-chain fatty acid content was 5092μg / ml, and the butyric acid content was 1541μg / ml.

[0120] Comparative Example 4

[0121] The composition comprises animal bifidobacterium and dietary fiber, wherein 1g of the probiotics contains 50 billion animal bifidobacteria, and the composition is prepared to contain 0.01g / ml animal bifidobacteria (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0122] Calculated in percentage by weight, the dietary fiber composition is as follows: 86% cereals and tubers, 14% prebiotics; the specific ingredients are 23% wheat bran, 4% barley bran, 22% rice bran, 5% buckwheat bran, 7% rye bran powder, 3% kudzu root powder, 15% potato fiber powder, 3% corn bran powder, 4% sorghum powder, 2% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 2% polydextrose.

[0123] The dietary fiber content of cereals and tubers in this dietary fiber combination is 39%, and the dietary fiber content of prebiotics is 13%, the ratio of the two is 3:1, and the total dietary fiber content of the two is 52%.

[0124] The ratio of the number of live animal Bifidobacterium to the total dietary fiber content was 194×10 8 cfu / g.

[0125] Through the in vitro fermentation model test simulating intestinal flora, the 16S sequencing of animal Bifidobacterium was 1.7×10 11 cfu / ml, the content of short-chain fatty acids was 2003μg / ml, and the content of butyric acid was 630μg / ml.

[0126] Comparative Example 5

[0127] Contains only animal Bifidobacterium, 1g of probiotics contains 50 billion animal Bifidobacterium, formulated to contain 0.01g / ml animal Bifidobacterium (the number of viable bacteria is 5×10 8 cfu / ml) solution.

[0128] Through the in vitro fermentation model test simulating intestinal flora, the 16S sequencing of animal Bifidobacterium was 9×10 10 cfu / ml, the short-chain fatty acid content was 964μg / ml, and the butyric acid content was 246μg / ml.

[0129] Comparative Example 6

[0130] The composition comprises a combination of Lactobacillus and dietary fiber, wherein 1 g of the probiotics contains 20 billion Lactobacillus, and the composition is prepared to contain 0.025 g / ml Lactobacillus (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0131] Calculated in percentage by weight, the dietary fiber composition is as follows: 86% cereals and tubers, 14% prebiotics; the specific ingredients are 23% wheat bran, 4% barley bran, 22% rice bran, 5% buckwheat bran, 7% rye bran powder, 3% kudzu root powder, 15% potato fiber powder, 3% corn bran powder, 4% sorghum powder, 2% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 2% polydextrose.

[0132] The dietary fiber content of cereals and tubers in this dietary fiber combination is 39%, and the dietary fiber content of prebiotics is 13%, the ratio of the two is 3:1, and the total dietary fiber content of the two is 52%.

[0133] The ratio of the number of viable Lactobacillus to the total dietary fiber content was 194×10 8 cfu / g.

[0134] The in vitro fermentation model test simulating intestinal flora showed that the 16S sequencing of Lactobacillus was 4.1×10 11 cfu / ml, the short-chain fatty acid content was 3974μg / ml, and the butyric acid content was 1047μg / ml.

[0135] Comparative Example 7

[0136] Contains only Lactobacillus acidophilus. 1g of probiotics contains 20 billion Lactobacillus acidophilus, and is formulated to contain 0.025g / ml Lactobacillus acidophilus (the number of viable bacteria is 5×10 8 cfu / ml) solution.

[0137] Through the in vitro fermentation model test simulating intestinal flora, the 16S sequencing of Lactobacillus was 1.4×10 11 cfu / ml, the content of short-chain fatty acids was 1563μg / ml, and the content of butyric acid was 438μg / ml.

[0138] Comparative Example 8

[0139] The composition comprises a combination of Lactobacillus rhamnosus and dietary fiber, wherein 1 g of the probiotic contains 100 billion Lactobacillus rhamnosus, and the composition is prepared to contain 0.005 g / ml Lactobacillus rhamnosus (the number of viable bacteria is 5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0140] Calculated in percentage by weight, the dietary fiber composition is as follows: 86% cereals and tubers, 14% prebiotics; the specific ingredients are 23% wheat bran, 4% barley bran, 22% rice bran, 5% buckwheat bran, 7% rye bran powder, 3% kudzu root powder, 15% potato fiber powder, 3% corn bran powder, 4% sorghum powder, 2% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 2% polydextrose.

[0141] The dietary fiber content of cereals and tubers in this dietary fiber combination is 39%, and the dietary fiber content of prebiotics is 13%, the ratio of the two is 3:1, and the total dietary fiber content of the two is 52%.

[0142] The ratio of the number of viable Lactobacillus rhamnosus to the total dietary fiber content was 194×10 8 cfu / g.

[0143] Through the in vitro fermentation model test simulating intestinal flora, the 16S sequencing of Lactobacillus rhamnosus was 1.1×10 11 cfu / ml, the content of short-chain fatty acids was 1840μg / ml, and the content of butyric acid was 598μg / ml.

[0144] Comparative Example 9

[0145] Contains only Lactobacillus rhamnosus. 1g of probiotics contains 100 billion Lactobacillus rhamnosus, and is formulated to contain 0.005g / ml Lactobacillus rhamnosus (the number of viable bacteria is 5×10 8 cfu / ml) solution.

[0146] Through the in vitro fermentation model test simulating intestinal flora, the 16S sequencing of Lactobacillus rhamnosus was 4×10 10 cfu / ml, the content of short-chain fatty acids was 1147μg / ml, and the content of butyric acid was 360μg / ml. Example 13

[0147] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotic contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.002 g / ml rat-derived Akkermansia muciniphila 139 bacteria (viable bacteria count is 1.2×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0148] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0149] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0150] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rat to total dietary fiber content was 39×10 8 cfu / g.

[0151] Through the in vitro fermentation model test simulating intestinal flora, the 16S sequencing of mouse Akkermansia muciniphila139 strain was 3×10 11 cfu / ml, the content of short-chain fatty acids was 3832μg / ml, and the content of butyric acid was 958μg / ml. Embodiment 14

[0152] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.006 g / ml rat-derived Akkermansia muciniphila 139 bacteria (viable bacteria count is 3×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0153] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0154] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0155] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 117×10 8 cfu / g.

[0156] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 4.6×10 11 cfu / ml, the short-chain fatty acid content was 4590μg / ml, and the butyric acid content was 1093μg / ml. Embodiment 15

[0157] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is formulated to contain 0.007 g / ml rat-derived Akkermansia muciniphila 139 bacteria (viable bacteria count is 3.5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0158] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0159] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0160] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 137×10 8 cfu / g.

[0161] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 5.8×10 11 cfu / ml, the short-chain fatty acid content was 4824μg / ml, and the butyric acid content was 1122μg / ml. Example 16

[0162] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotic contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.008 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 4×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0163] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0164] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0165] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 156×10 8 cfu / g.

[0166] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 6.8×10 11 cfu / ml, the content of short-chain fatty acids was 5106μg / ml, and the content of butyric acid was 1160μg / ml. Embodiment 17

[0167] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.012 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 6×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0168] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0169] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0170] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 234×10 8 cfu / g.

[0171] Through the in vitro fermentation model test simulating intestinal flora, the 16S sequencing of mouse Akkermansia muciniphila139 strain was 7×10 11 cfu / ml, the short-chain fatty acid content was 5344μg / ml, and the butyric acid content was 1188μg / ml. Embodiment 18

[0172] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.013 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 6.5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0173] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0174] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0175] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 254×10 8 cfu / g.

[0176] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 7.5×10 11 cfu / ml, the content of short-chain fatty acids was 5102μg / ml, and the content of butyric acid was 1063μg / ml. Embodiment 19

[0177] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.014 g / ml rat-derived Akkermansia muciniphila 139 bacteria (viable bacteria count is 7×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0178] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0179] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0180] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 273×10 8 cfu / g.

[0181] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 7.7×10 11 cfu / ml, the content of short-chain fatty acids was 5004μg / ml, and the content of butyric acid was 1001μg / ml. Embodiment 20

[0182] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.015 g / ml rat-derived Akkermansia muciniphila 139 bacteria (viable bacteria count is 7.5×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0183] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0184] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0185] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rat to total dietary fiber content was 293×10 8 cfu / g.

[0186] Through the in vitro fermentation model test simulating intestinal flora, the 16S sequencing of mouse Akkermansia muciniphila139 strain was 8×10 11 cfu / ml, the short-chain fatty acid content was 4736μg / ml, and the butyric acid content was 877μg / ml. Embodiment 21

[0187] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.016 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 8×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0188] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0189] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0190] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 312×10 8 cfu / g.

[0191] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 8.1×10 11 cfu / ml, the short-chain fatty acid content was 4772μg / ml, and the butyric acid content was 852μg / ml. Embodiment 22

[0192] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.018 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 9×10 8 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0193] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0194] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0195] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 351×10 8 cfu / g.

[0196] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 8.4×10 11 cfu / ml, the short-chain fatty acid content was 4238μg / ml, and the butyric acid content was 731μg / ml. Embodiment 23

[0197] A composition comprising a rat-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component, wherein 1 g of the probiotics used contains 50 billion rat-derived Akkermansia muciniphila 139 bacteria, and the composition is prepared to contain 0.02 g / ml rat-derived Akkermansia muciniphila 139 bacteria (the number of viable bacteria is 1×10 9 cfu / ml), and 0.05g / ml dietary fiber combination component solution.

[0198] Calculated in percentage by weight, the dietary fiber composition is as follows: 81% cereals and tubers, 19% prebiotics; the specific ingredients are 16% wheat bran, 5% oat bran, 4% barley bran, 19% rice bran, 4% coix seed powder, 11% rye bran powder, 5% kudzu root powder, 5% potato fiber powder, 6% sweet potato fiber powder, 6% corn bran powder, 5% resistant dextrin, 3% inulin, 3% fructooligosaccharides, 4% xylo-oligosaccharides, and 4% polydextrose.

[0199] The dietary fiber content of cereals and tubers in this dietary fiber combination is 34%, and the dietary fiber content of prebiotics is 17%, the ratio of the two is 2:1, and the total dietary fiber content of the two is 51%.

[0200] The ratio of viable bacterial count of Akkermansia muciniphila 139 strain from rats to total dietary fiber content was 390×10 8 cfu / g.

[0201] The 16S sequencing of Akkermansia muciniphila139 strain from mice was 8.3×10 11 cfu / ml, the short-chain fatty acid content was 3885μg / ml, and the butyric acid content was 648μg / ml.

[0202] The above examples and comparative examples are summarized into the following Tables 1 to 8, and a scatter plot of short-chain fatty acid content is prepared based on the data of the short-chain fatty acid content after fermentation and the ratio of the viable count of Akkermansia muciniphila 139 strain from rats to the total dietary fiber content in Examples 1 to 23 in the Tables, namely: Figure 1 .

[0203] Table 1

[0204]

[0205] Table 2

[0206]

[0207] Table 3

[0208]

[0209] Table 4

[0210] Table 5

[0211]

[0212] Table 6

[0213]

[0214] Table 7

[0215]

[0216] Table 8

[0217]

[0218] Further research was conducted to determine the relationship between the dietary fiber content of cereals and tubers and the dietary fiber content of prebiotics and the experimental results. The specific research results are listed in Tables 9 to 14 below:

[0219] Table 9

[0220]

[0221] Table 10

[0222]

[0223] Table 11

[0224]

[0225] Table 12

[0226]

[0227] Table 13

[0228]

[0229] Table 14

[0230]

[0231] The preferred specific embodiments of the present invention are described in detail above. It should be understood that ordinary technicians in the field can make many modifications and changes based on the concept of the present invention without creative work. Therefore, all technical solutions that can be obtained by technicians in the technical field based on the concept of the present invention through logical analysis, reasoning or limited experiments on the basis of the prior art should be within the scope of protection determined by the claims.

Claims

1. A composition comprising Akkermansia muciniphila 139 strain of mouse origin and a dietary fiber combination component, characterized in that: The ratio of the viable bacterial count of the mouse-derived Akkermansia muciniphila 139 strain to the total dietary fiber content in the dietary fiber combination component is 180×10 8 cfu:1g~220 ×10 8 cfu: 1g; the dietary fiber combination comprises cereals and tubers and prebiotics; in terms of weight percentage, the cereals and tubers are selected from 0-23% wheat bran, 0-18% oat bran, 0-22% highland barley bran, 0-30% rice bran, 0-18% tartary buckwheat bran, 0-9% coix seed powder, 0-18% sweet buckwheat powder, 0-14% rye flour, 0-20% rye bran powder, 0-14% yam powder, 0-16% kudzu root powder, 0-30% potato fiber powder, 0-29 % sweet potato fiber powder, 0-15% corn bran powder, 0-14% corn flour, 0-11% sorghum flour or more; the prebiotics are selected from 0-12% resistant dextrin, 0-13% inulin, 0-16% oligofructose, 0-10% oligoxylose, 0-15% polydextrose or one or more; the dietary fiber combination comprises insoluble dietary fiber and soluble dietary fiber, and the mass ratio of the insoluble dietary fiber to the soluble dietary fiber is 1:1-4:1 or 9:1-10:

1.

2. The composition according to claim 1, characterized in that The mass ratio of the insoluble dietary fiber to the soluble dietary fiber is 2:1 or 9.5:

1.

3. Use of the composition comprising the mouse-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component as described in any one of claims 1 to 2 in the preparation of a drug for promoting intestinal production of short-chain fatty acids.

4. The use according to claim 3, characterized in that The composition comprising the mouse-derived Akkermansia muciniphila139 strain and dietary fiber combination components is used in promoting intestinal butyrate production.

5. Use of the composition comprising the mouse-derived Akkermansia muciniphila 139 strain and a dietary fiber combination component as claimed in any one of claims 1 to 4 in the preparation of a medicament for controlling postprandial blood sugar and adjusting the intestinal flora structure.

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