Prebiotic formulation and method of configuration

Abstract

The application relates to the technical field of biological medicine, in particular to a composition, a synbiotic composition, a metabiotic composition, a pharmaceutical composition and a dietary supplement containing the same. The application also provides a preparation method of the composition and a use of the composition in the preparation of a medicine.

Description

Technical Field

[0001] This application relates to the field of biomedical technology, specifically to a composition comprising a synbiotic composition, a postbiotic composition, a pharmaceutical composition, and a dietary supplement. This application also provides methods for their preparation and their use in the preparation of pharmaceuticals. Background Technology

[0002] Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are common chronic intestinal diseases worldwide. Patients often experience symptoms such as abdominal pain, bloating, diarrhea, constipation, gut microbiota imbalance, and chronic inflammation, which seriously affect their emotional health and quality of life. Recent studies have found that gut microbiota dysbiosis, altered intestinal motility, increased intestinal sensitivity, impaired intestinal barrier function, and immune system abnormalities are important factors in the occurrence and development of IBS and IBD.

[0003] Prebiotic therapy is an effective approach in the management of IBS and IBD. However, most prebiotics currently on the market may exacerbate symptoms in IBS and IBD patients (such as causing bloating and abdominal pain), making it difficult for them to benefit from the gut health benefits of prebiotics. Therefore, developing prebiotics specifically designed for IBS and IBD patients and other individuals with weakened digestive systems, which can improve gut microbiota, enhance immune function, maintain intestinal barrier stability, and improve mood without inducing abdominal discomfort, is key to addressing this issue.

[0004] Furthermore, most prebiotic products typically only act on the terminal jejunum and part of the proximal colon, failing to cover the distal colon. Improving gut health requires comprehensive coverage of the entire colon to promote balanced growth of the gut microbiota and optimize the gut microecological environment. Meanwhile, modern research indicates that the regulation of the gut microbiota not only affects the digestive system but is also closely related to immune regulation and metabolic health (such as blood sugar control). Therefore, developing a prebiotic formula that covers the entire colon and provides comprehensive health benefits is of great significance for patients with IBS and IBD, as well as for a broader healthy population. Summary of the Invention

[0005] The applicant of this application has provided a composition comprising multiple prebiotics through extensive experimentation. This application further adds probiotics (e.g., Bifidobacterium adolescentis, Lactobacillus reuteri) to the above composition, thereby providing a synbiotic. The composition and synbiotic of this application can effectively improve irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) in subjects, and can reduce the inflammation level and improve the gut microbiota of subjects.

[0006] Therefore, in a first aspect, this application provides a composition comprising the following components: resistant dextrin, partially hydrolyzed guar gum (PHGG), polydextrose, and β-glucan.

[0007] The applicant of this application found that a combination of resistant dextrin, partially hydrolyzed guar gum (PHGG), polydextrose, and β-glucan significantly improved irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) in subjects, particularly when they were combined in the following proportions.

[0008] For example, in some embodiments, the composition comprises, by weight, 10-50 parts resistant dextrin, 10-40 parts PHGG, 5-30 parts polydextrin, and 10-45 parts β-glucan. In some embodiments, the composition comprises, by weight, 20-50 parts resistant dextrin, 10-40 parts PHGG, 10-20 parts polydextrin, and 10-30 parts β-glucan. In some embodiments, the composition comprises, by weight, 25-50 parts resistant dextrin, 10-35 parts PHGG, 10-20 parts polydextrin, and 10-25 parts β-glucan.

[0009] It is understood that β-glucan can be derived from any organism. In some embodiments, the β-glucan is selected from oat β-glucan, yeast β-glucan, mushroom β-glucan, algal β-glucan, or any combination thereof.

[0010] Furthermore, this application specifically verified the efficacy of the dextran being a combination of oat β-glucan and yeast β-glucan, which showed significant therapeutic effects in improving IBS and IBD in subjects. In some embodiments, the composition comprises the following components: resistant dextrin, PHGG, polydextrose, oat β-glucan, and yeast β-glucan.

[0011] It should be understood that one of the contributions of this application is the combined use of the various components in the above composition, which have a synergistic effect. This application demonstrates that removing one or two components of the above composition, or replacing one or two components of the composition with other prebiotic components, will significantly reduce the effectiveness of the composition.

[0012] For example, removing oat beta-glucan and yeast beta-glucan, or replacing them with equal amounts of inulin and fructooligosaccharides, significantly reduces the effectiveness in relieving bloating and improving stool consistency, and may even worsen symptoms and cause intolerance reactions (Example 2). For example, removing polydextrose and oat beta-glucan significantly reduces the effectiveness in relieving urgency and regulating bowel movements (Example 3). For example, removing resistant dextrin and oat beta-glucan and replacing them with equal amounts of inulin and fructooligosaccharides worsens symptoms and causes intolerance reactions (Example 3).

[0013] Furthermore, this application contributes by providing suitable proportions of the various components in the composition. Those skilled in the art, guided by this application, can flexibly adjust the proportions of each component within a suitable range, based on the condition and needs of the subject.

[0014] In some embodiments, the composition comprises, by weight, the following components: 10-50 parts resistant dextrin, 10-40 parts PHGG, 5-30 parts polydextrin, 5-25 parts oat β-glucan, and 5-20 parts yeast β-glucan.

[0015] In some embodiments, the composition comprises, by weight, the following components: 20-50 parts resistant dextrin, 10-40 parts PHGG, 10-20 parts polydextrose, 5-20 parts oat β-glucan, and 5-10 parts yeast β-glucan.

[0016] In some embodiments, the composition comprises, by weight, the following components: 25-50 parts resistant dextrin, 10-35 parts PHGG, 10-20 parts polydextrose, 5-15 parts oat β-glucan, and 5-10 parts yeast β-glucan.

[0017] Furthermore, this application contributes by providing a composition containing a greater number of different ingredients (including nine ingredients). Those skilled in the art will understand that even if these ingredients, when administered individually, may have a beneficial effect on the subject, interactions between the different ingredients may occur when they are combined, thereby reducing the effectiveness of the administration or even causing adverse effects on the subject. For example, some ingredients may compete for the same nutrients or receptor sites, thereby reducing the effect of other ingredients; or some ingredients may promote the production of metabolites, inhibiting the effects of other ingredients. Therefore, the applicant of this application has made extensive attempts to provide the composition of this application.

[0018] In some embodiments, the composition further includes, by weight, gum arabic, resistant starch, pectin, and rhamnose.

[0019] In some embodiments, the composition comprises, by weight, the following components: 25-50 parts resistant dextrin, 10-35 parts PHGG, 10-20 parts polydextrose, 5-15 parts oat β-glucan, 5-10 parts yeast β-glucan, 10-50 parts gum arabic, 5-50 parts resistant starch, 10-30 parts pectin, and 5-30 parts rhamnose.

[0020] In some embodiments, the composition comprises, by weight, the following components: 25-50 parts resistant dextrin, 10-35 parts PHGG, 10-20 parts polydextrose, 5-15 parts oat β-glucan, 5-10 parts yeast β-glucan, 10-40 parts gum arabic, 10-20 parts resistant starch, 5-15 parts pectin, and 10-20 parts rhamnose.

[0021] In some embodiments, the composition comprises, by weight, the following components: 25-50 parts resistant dextrin, 10-35 parts PHGG, 10-20 parts polydextrose, 5-15 parts oat β-glucan, 5-10 parts yeast β-glucan, 15-40 parts gum arabic, 10-20 parts resistant starch, 5-15 parts pectin (e.g., 10 parts), and 10-15 parts rhamnose.

[0022] In some embodiments, the composition comprises, or consists of, the following components in parts by weight: resistant dextrin, PHGG, polydextrose, oat beta-glucan, and yeast beta-glucan.

[0023] In some embodiments, the composition comprises, by weight, or consists of, the following components: resistant dextrin, PHGG, polydextrose, oat beta-glucan, yeast beta-glucan, gum arabic, resistant starch, pectin, and rhamnose.

[0024] In some embodiments, the composition does not contain fructooligosaccharides (FOS), galactooligosaccharides (GOS), xylooligosaccharides, inulin, lactose, sorbitol, fructan, mannitol, and / or wheat hulls. In some embodiments, the composition does not contain fructooligosaccharides (FOS) and inulin.

[0025] In some embodiments, the composition comprises low amounts (e.g., up to 3 parts by weight, up to 2 parts by weight, or up to 1 part by weight) of fructooligosaccharides (FOS), galactooligosaccharides (GOS), xylooligosaccharides, inulin, lactose, sorbitol, fructan, mannitol, and / or wheat hulls.

[0026] The term "synbiotics" refers to a mixture of preparations. According to the International Scientific Association for Probiotics and Prebiotics (ISAPP), a synbiotic is a mixture of live microorganisms and substrates that can be selectively utilized by the host microorganisms and provide health benefits to the host. In some embodiments, synbiotics include probiotics and prebiotics.

[0027] On the other hand, this application provides a synbiotic composition comprising the composition described above, and probiotics.

[0028] The term "probiotics" refers to a class of microorganisms. Probiotics are live microorganisms that are beneficial to the host, for example, by colonizing the human body and altering the composition of the host's gut microbiota. Common probiotics include Bifidobacterium, Lactobacillus, yeasts, Pediococcus lactis, and Streptococcus thermophilus.

[0029] In some embodiments, the probiotics are selected from bacteria, fungi (e.g., yeast), or any combination thereof.

[0030] In some embodiments, the probiotics are selected from Lactobacillus, Bifidobacterium, Bacillus, Propionibacterium, Streptococcus, Lactococcus, Pediococcus, Enterococcus, Staphylococcus, or any combination thereof.

[0031] In some embodiments, the probiotic is Bifidobacterium adolescentis (Bifidobacterium adolescentis). Bifidobacterium adolescents is ) and Lactobacillus reuteri ( Lactobacillus reuteri ).

[0032] In some embodiments, the ratio of Bifidobacterium adolescentis to Lactobacillus reuteri is 1:3 to 3:1 (e.g., 1:3 to 1:2, 1:2 to 1:1, 1:1 to 2:1, 2:1 to 3:1).

[0033] In some embodiments, the probiotics are in a concentration of 10... 6 Up to 10 12 The amount of CFU / dose present.

[0034] The term "postbiotic," also known as postbiotic, is a mixed preparation. According to the definition in "Probiotic Products - Lactic Acid Bacteria - Postbiotics," a postbiotic is "a product containing inactivated microorganisms and / or bacterial components with a clearly defined genetic background that are beneficial to the host's health, including or excluding their metabolites; excluding chemically synthesized components and viruses / bacteriophages and their products." Therefore, postbiotics can include inactivated whole bacterial cells, bacterial components (e.g., teichoic acid, cell surface proteins, membrane proteins), or bacterial metabolites (e.g., peptides, short-chain fatty acids, cellular polysaccharides).

[0035] On the other hand, this application provides a postbiotic composition comprising the composition as described above, as well as probiotics, components of probiotics, and / or metabolites of probiotics.

[0036] In some embodiments, the probiotics are selected from bacteria, fungi (e.g., yeast), or any combination thereof.

[0037] In some embodiments, the probiotics are selected from Lactobacillus, Bifidobacterium, Bacillus, Propionibacterium, Streptococcus, Lactococcus, Pediococcus, Enterococcus, Staphylococcus, or any combination thereof.

[0038] In some embodiments, the probiotic is Bifidobacterium adolescentis (Bifidobacterium adolescentis). Bifidobacterium adolescents is ) and Lactobacillus reuteri ( Lactobacillus reuteri ).

[0039] In some embodiments, the ratio of Bifidobacterium adolescentis to Lactobacillus reuteri is 1:3 to 3:1 (e.g., 1:3 to 1:2, 1:2 to 1:1, 1:1 to 2:1, 2:1 to 3:1).

[0040] In some implementations, the probiotics are dead bacteria.

[0041] In some embodiments, the resistant dextrin, PHGG, polydextrose, oat β-glucan, and yeast β-glucan in the synbiotic composition are 15-35 parts, 15-35 parts, 10-30 parts, 5-25 parts, and 5-25 parts, respectively, calculated by weight.

[0042] In another aspect, this application provides pharmaceutical compositions comprising the compositions described above, the synbiotic compositions described above, or the postbiotic compositions described above.

[0043] In some embodiments, the pharmaceutical composition further includes additional active ingredients.

[0044] In some embodiments, the additional active ingredient is capable of treating and / or improving intestinal diseases in the subject.

[0045] In some embodiments, the intestinal disease is selected from diseases and / or symptoms associated with irritable bowel syndrome (IBS) and / or inflammatory bowel disease (IBD).

[0046] In some embodiments, the disease is selected from Crohn's disease, ulcerative colitis, primary sclerosing cholangitis (PSC), erythema nodosum, pyoderma gangrenosa, uveitis, scleritis, peripheral or axial spondyloarthritis, venous thromboembolism, colorectal cancer, or any combination thereof.

[0047] In some implementations, the symptoms are selected from abdominal pain, bloating, urgency to defecate, constipation, diarrhea, weight loss, perianal lesions, mood disorders, growth retardation, or any combination thereof.

[0048] In some embodiments, the pharmaceutical composition further includes a pharmaceutically acceptable carrier and / or excipient.

[0049] In some embodiments, the pharmaceutical composition is in the form of a solution, suspension, powder, tablet, pill, emulsion, gel, capsule, granule, elixir, lozenge, suppository, injection, inhaler, or spray.

[0050] On the other hand, this application provides dietary supplements comprising the compositions described above, the synbiotic compositions described above, the postbiotic compositions described above, or the pharmaceutical compositions described above.

[0051] In some implementations, the dietary supplement may also include additional excipients.

[0052] In some embodiments, the additional excipients are selected from food additives, food processing aids, nutritional fortifiers, or any combination thereof.

[0053] In some embodiments, the food additive is selected from sweeteners, acidity regulators, food flavorings, or any combination thereof.

[0054] In some embodiments, the additional excipients are selected from: honey, xylitol, erythritol, citric acid, DL-malic acid, pectin, maltodextrin, resistant dextrin, vitamin C, vitamin E, calcium, iron, zinc, or any combination thereof.

[0055] In some implementations, the dietary supplement is selected from dried foods, pressed foods, puffed foods, and baked foods.

[0056] In some embodiments, the dietary supplement is selected from solid beverages (e.g., solid beverage powder, solid beverage granules), freeze-dried blocks, freeze-dried powders, candies, or liquid beverages (e.g., ready-to-drink juice, concentrated juice).

[0057] It is understood that the compositions described in this application are not limited to any particular state, shape, or form. The compositions of this application can be prepared in any desired state. The compositions of this application can be prepared in any usable state, such as a liquid for drinking, a powder for eating, granules, or other solid form. The compositions of this application can also be added to other foods or pharmaceuticals to exert their effects.

[0058] In another aspect, this application provides a method for preparing the composition as described above, the synbiotic composition as described above, the postbiotic composition as described above, the pharmaceutical composition as described above, or the dietary supplement as described above, comprising: providing each component of the composition as described above.

[0059] In some embodiments, the method includes: providing and mixing the various components of the composition as described above in proportion.

[0060] In some embodiments, the method further includes dissolving the individual components of the composition in a solvent (e.g., water).

[0061] In some embodiments, the method further includes preparing the composition into granules or powder (e.g., by spray drying).

[0062] In some embodiments, the composition can be prepared by directly mixing the individual components together. In some embodiments, the composition is mixed under low-temperature conditions.

[0063] In some embodiments, the composition is dissolved in a solvent (e.g., water) and sterilized to obtain a drinkable form of the composition. In some embodiments, the composition is sheared and homogenized prior to dissolution.

[0064] In some embodiments, the individual components of the composition are mixed together and processed to obtain the composition in granular or powder form. In some embodiments, the processing includes spray drying.

[0065] On the other hand, this application provides the use of the composition described above, the synbiotic composition described above, the postbiotic composition described above, the pharmaceutical composition described above, or the dietary supplement described above in the preparation of a medicine for treating and / or improving intestinal diseases in a subject.

[0066] In some embodiments, the intestinal disease is selected from diseases and / or symptoms associated with irritable bowel syndrome (IBS) and / or inflammatory bowel disease (IBD).

[0067] In some embodiments, the disease is selected from Crohn's disease, ulcerative colitis, primary sclerosing cholangitis (PSC), erythema nodosum, pyoderma gangrenosa, uveitis, scleritis, peripheral or axial spondyloarthritis, venous thromboembolism, colorectal cancer, or any combination thereof.

[0068] In some implementations, the symptoms are selected from abdominal pain, bloating, urgency to defecate, constipation, diarrhea, weight loss, perianal lesions, mood disorders, growth retardation, or any combination thereof.

[0069] In some implementations, the subject is a mammal.

[0070] In some embodiments, the mammal is selected from rats, pigs, rabbits, monkeys, sheep, and humans.

[0071] Terminology Definition

[0072] In this invention, unless otherwise stated, the scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. Furthermore, the operational steps used herein, such as molecular genetics, nucleic acid chemistry, chemistry, molecular biology, biochemistry, cell culture, microbiology, cell biology, genomics, and recombinant DNA, are all conventional steps widely used in their respective fields. To better understand this invention, definitions and explanations of relevant terms are provided below.

[0073] Each component in the composition of this application is an acceptable raw material for food or pharmaceuticals and is commercially available. Based on the disclosure of this application, those skilled in the art are already able to obtain each component and select commercially available specifications of each component that meet the requirements according to conventional standards. That is, the scope of protection of this application is not limited to the specific source or brand of each component used, nor is it necessary to further disclose its specific source or brand in this application.

[0074] As used in this article, the term "PHGG" is an abbreviation for Partially Hydrolyzed Guar Gum, also known as galactomannan, which is a naturally sourced, water-soluble, fermentable dietary fiber.

[0075] As used herein, the term "β-glucan" refers to a polysaccharide composed of glucose molecules linked by β-1,3 and β-1,6 glycosidic bonds. β-glucans are naturally found in a variety of organisms, such as yeast, oats, mushrooms, and algae; these biologically derived β-glucans are collectively referred to as yeast β-glucan, oat β-glucan, mushroom β-glucan, and algal β-glucan, respectively.

[0076] As used in this article, the term "oat β-glucan" is a polysaccharide, also known as β-(1→3, 1→4) glucan from oats. It has been found in oats (… Avena sativa L.) in the endosperm and aleurone layer cell walls of the grain.

[0077] As used in this article, the term "yeast β-glucan" is a polysaccharide found in Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae Inner layer of the cell wall.

[0078] As used herein, the term "CFU / dosage" refers to the amount of bacteria present in a composition / food product or dietary supplement / pharmaceutical composition provided to a subject daily or per dose. For example, in some embodiments, the probiotics in the synbiotic composition are present at a concentration of 10... 6 Up to 10 12 The amount of CFU / dose present (e.g., 10) 8 Up to 10 12 CFU / dosage). In this embodiment, if the synbiotic composition is applied to a food product (e.g., in a solid beverage, yogurt), the food product (e.g., a solid beverage, yogurt) provided to the subject daily or per dose may contain approximately 10 CFU / dosage. 6 Up to 10 12 CFU of probiotics. Alternatively, this amount can be divided into multiple administrations, provided that the total amount of probiotics received by the subject at any given time (e.g., every 24-hour period) is less than approximately 10. 6 To about 10 12 CFU, which means the probiotics in the above-mentioned synbiotic composition are at a concentration of 10... 6 Up to 10 12 The amount of CFU / dose present (e.g., 10) 8 Up to 10 12 CFU / dosage).

[0079] As used herein, the term "pharmaceutically acceptable carrier and / or excipient" refers to a carrier and / or excipient that is pharmacologically and / or physiologically compatible with the subject and the active ingredient, which is well known in the art and includes, but is not limited to: pH adjusters, surfactants, adjuvants, ionic strength enhancers, diluents, osmotic pressure maintaining agents, absorption delaying agents, and preservatives. For example, pH adjusters include, but are not limited to, phosphate buffers. Surfactants include, but are not limited to, cationic, anionic, or nonionic surfactants, such as Tween-80. Ionic strength enhancers include, but are not limited to, sodium chloride. Preservatives include, but are not limited to, various antibacterial and antifungal agents, such as parabens, chlorobutanol, phenol, sorbic acid, etc. Osmotic pressure maintaining agents include, but are not limited to, sugars and NaCl. Absorption delaying agents include, but are not limited to, monostearates and gelatin. Diluents include, but are not limited to, water, aqueous buffers (such as buffered saline), alcohols, and polyols (such as glycerol). Preservatives include, but are not limited to, various antibacterial and antifungal agents, such as thimerosal, 2-phenoxyethanol, p-hydroxybenzoate, chlorobutanol, phenol, sorbic acid, etc. Stabilizers have the meaning commonly understood by those skilled in the art, which stabilize the desired activity of the active ingredient in a pharmaceutical product, including but not limited to monosodium glutamate, gelatin, SPGA, sugars (such as sorbitol, mannitol, starch, sucrose, lactose, dextran, or glucose), amino acids (such as glutamic acid, glycine), proteins (such as dried whey, albumin, or casein) or their degradation products (such as lactalbumin hydrolysate), etc.

[0080] As used herein, the term "subject" refers to a mammal, such as a human, cynomolgus monkey, mouse, pig, rabbit, or sheep. In some embodiments, the subject has a disease and / or symptoms associated with venous insufficiency, or is at risk of having such a disease.

[0081] As used herein, the term "treatment" refers to a method performed to obtain a beneficial or desired clinical outcome. For the purposes of this application, a beneficial or desired clinical outcome includes, but is not limited to, alleviating symptoms, reducing the extent of disease, stabilizing (i.e., no longer worsening) the state of disease, delaying or slowing the progression of disease, improving or alleviating the state of disease, relieving symptoms (whether partial or complete), alleviating or improving prognosis, reducing or inhibiting disease recurrence, whether detectable or undetectable. Furthermore, "treatment" can also refer to prolonged survival compared to expected survival (if no treatment was received).

[0082] Beneficial effects

[0083] The applicant of this application has provided a composition comprising multiple prebiotics through extensive experimentation. This application further adds probiotics (e.g., Bifidobacterium adolescentis, Lactobacillus reuteri) to the above composition, thereby providing a synbiotic. The composition and synbiotic of this application have at least the following effects: (1) It can effectively improve irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) in subjects; (2) It can effectively improve symptoms such as abdominal distension, constipation, urgency, diarrhea, abdominal pain, weight loss, and high inflammation levels in the subjects; (3) It can reduce the inflammation level of the subjects (e.g., it can significantly reduce spleen weight and increase colon length). (4) It can cover the distal colon, improve the gut microbiota of the subjects, increase the level of short chain fatty acids (SCFAs), increase the diversity of gut microbiota and increase the level of beneficial bacteria; (5) It has a rapid onset of action (e.g., significant therapeutic effect can be produced in seven days), no toxic side effects, and is well tolerated by subjects, which is significantly better than other formulations.

[0084] On the other hand, this application also verifies the synergistic effect between the various components in the composition of this application. For example, removing only one or two components from the composition of this application significantly reduces its effect. Alternatively, replacing one or two components in the composition of this application with other components (e.g., fructooligosaccharides, inulin) significantly reduces its effect and may even aggravate the symptoms of the subjects.

[0085] Therefore, this application provides a scientifically effective solution for improving gut health and overall metabolic health.

[0086] The embodiments of the present invention will now be described in detail with reference to the accompanying drawings and examples. However, those skilled in the art will understand that the following drawings and examples are for illustrative purposes only and are not intended to limit the scope of the invention. Various objects and advantages of the present invention will become apparent to those skilled in the art from the following detailed description of the drawings and preferred embodiments. Attached Figure Description

[0087] Figure 1 This shows the process of constructing a mouse IBD model.

[0088] Figure 2 The results show the mortality rate of the mice.

[0089] Figure 3 The results show the weight of the mice.

[0090] Figure 4 The results show the spleen weight of the mice.

[0091] Figure 5 The results show the colon length of the mice.

[0092] Figure 6 The results of serum metabolite analysis are shown in the prebiotic-treated mice.

[0093] Figure 7 The results of serum metabolite analysis in mice treated with synbiotics are shown.

[0094] Figure 8 This shows the results of a diversity analysis of the gut microbiota in mice treated with prebiotics.

[0095] Figure 9 This shows the results of a diversity analysis of the gut microbiota in mice treated with prebiotics.

[0096] Figure 10 This shows the results of the gut microbiota diversity analysis in mice treated with synbiotics.

[0097] Figure 11 This shows the results of the diversity analysis among the gut microbiota of mice treated with synbiotics.

[0098] Figure 12 This shows the results of differential gut microbiota analysis in mice treated with synbiotics. Detailed Implementation

[0099] The invention will now be described with reference to the following examples, which are intended to illustrate the invention (and not limit it). Unless otherwise specified, the molecular biology experimental methods and immunoassays used in this invention are substantially in accordance with the methods described in J. Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Edition, Cold Spring Harbor Laboratory Press, 1989, and FM Ausubel et al., A Concise Guide to Laboratory Molecular Biology, 3rd Edition, John Wiley & Sons, Inc., 1995.

[0100] Furthermore, unless specific conditions are specified in the examples, conventional conditions or conditions recommended by the manufacturer should be followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products. Those skilled in the art will understand that the examples are described by way of illustration and are not intended to limit the scope of protection claimed by the invention. All disclosures and other references mentioned herein are incorporated herein by reference in their entirety.

[0101] Example 1.

[0102] The materials involved in this application include: resistant dextrin, PHGG, polydextrose, oat beta-glucan, yeast beta-glucan, gum arabic, resistant starch, pectin, rhamnose, inulin, and fructooligosaccharides.

[0103] This application relates to the Bristol Stool Scale, a medical assessment tool. This scale classifies human stool into seven types based on its morphology, assessing the time stool remains in the large intestine and intestinal health by observing its characteristics: Type I (nut-shaped stool) and Type II (hard, dry stool) indicate constipation; Type III (wrinkled stool) and Type IV (banana-shaped stool) are ideal; and Type V (soft stool), Type VI (slightly formed stool), and Type VII (watery stool) indicate diarrhea.

[0104] Example 2.

[0105] To investigate the effects of a prebiotic formulation composed of five ingredients—resistant dextrin, PHGG, polydextrose, oat β-glucan, and yeast β-glucan—we studied the effects of administering different prebiotic formulations to patients.

[0106] Patient information: A woman with long-term IBS-C (constipation-predominant irritable bowel syndrome), who suffers from abdominal bloating and difficulty defecating.

[0107] (1) Treatment Formula 1: a. Resistant dextrin: 40 parts by weight b. PHGG (partially hydrolyzed guar gum, galactomannan): 30 parts by weight c. Polydextrose: 20 parts by weight d. Oat beta-glucan: 10 parts by weight e. Yeast β-glucan: 10 parts by weight (2) Treatment Formula 2 (without oat beta-glucan and yeast beta-glucan): a. Resistant dextrin: 40 parts by weight b. PHGG (partially hydrolyzed guar gum, galactomannan): 30 parts by weight c. Polydextrose: 20 parts by weight (3) Treatment Formula 3 (free of oat beta-glucan and yeast beta-glucan, and contains fructooligosaccharides and inulin): a. Resistant dextrin: 40 parts by weight b. PHGG (partially hydrolyzed guar gum, galactomannan): 30 parts by weight c. Polydextrose: 20 parts by weight d. Fructooligosaccharides: 10 parts by weight e. 10 parts by weight of inulin (4) Preparation method: The above raw materials are mixed in proportion by weight, stirred evenly under low temperature drying conditions, and then sieved to obtain a powdered prebiotic composition (compound powder).

[0108] (5) Effects of use: Treatment Formula 1: After taking this formula for 14 consecutive days, the abdominal bloating was significantly relieved, the frequency of bowel movements improved from once every 3 days to once a day, the stool shape returned to normal, there were no side effects such as abdominal pain or diarrhea, and the symptoms did not recur.

[0109] Treatment Formula 2: After taking this formula for 14 consecutive days, the abdominal bloating was not significantly relieved, the stool shape improved and the frequency of defecation increased, but the effect was not as good as Treatment Formula 1. There were no side effects such as abdominal pain and diarrhea.

[0110] Treatment formula 3: After taking 10g of this formula daily, the abdominal distension was relieved and the stool form was improved, but abdominal pain and bloating occurred. After taking it for 5 days, the patient refused to take it.

[0111] The specific results are shown in Table 1.

[0112] Table 1. Patient Information

[0113] The above results demonstrate that the composition of this application effectively improves symptoms such as bloating and constipation caused by irritable bowel syndrome and inflammatory bowel disease, with no side effects and high patient tolerance. Formula 2, which does not contain oat β-glucan and yeast β-glucan, is less effective, and Formula 3, which contains both fructooligosaccharides and inulin, may even cause side effects in patients. This further illustrates the synergistic effect between the components of the composition of this application, as well as the safety of the composition.

[0114] Example 3.

[0115] To investigate the effects of a prebiotic formulation composed of five ingredients—resistant dextrin, PHGG, polydextrose, oat β-glucan, and yeast β-glucan—we studied the effects of administering different prebiotic formulations to patients.

[0116] Patient information: A 30-year-old male with IBS-D (diarrhea-predominant irritable bowel syndrome), experiencing 3-5 episodes of diarrhea daily, usually related to diet, accompanied by urgency.

[0117] (1) Treatment Formula 1: a. Resistant dextrin: 25 parts by weight b. PHGG: 35 parts by weight c. Polydextrose: 10 parts by weight d. Oat beta-glucan: 10 parts by weight e. Yeast β-glucan: 5 parts by weight (2) Treatment Formula 2 (without polydextrose and oat beta-glucan): a. Resistant dextrin: 25 parts by weight b. PHGG: 35 parts by weight c. Yeast β-glucan: 5 parts by weight (3) Treatment Formula 3 (containing no resistant dextrin or yeast β-glucan, but containing fructooligosaccharides and inulin): a.PHGG: 35 parts by weight b. Polydextrose: 10 parts by weight c. Oat beta-glucan: 10 parts by weight d. Fructooligosaccharides: 10 parts by weight e. Inulin: 10 parts by weight (4) Preparation method: Mix the ingredients thoroughly according to the above proportions, place them in a sealed package, and store at room temperature away from light.

[0118] (5) Effects of use: Treatment Formula 1: Take this formula twice a day for 10 consecutive days. After that, the frequency of bowel movements will decrease, the stool will return to normal, there will be no diarrhea or abdominal pain, and the quality of life will be significantly improved.

[0119] Treatment Formula 2: Take this formula twice a day for 10 consecutive days. After taking it for 10 consecutive days, the diarrhea will improve, but there will still be occasional loose stools and urgency.

[0120] Treatment Formula 3: Take this formula twice a day. After 3 days of use, if the symptoms of diarrhea and urgency do not improve, the stool may even worsen, and abdominal pain may occur.

[0121] The results are shown in Table 2.

[0122] Table 2. Patient Information

[0123] The above results demonstrate that the composition of this application can effectively improve symptoms such as diarrhea and urgency caused by irritable bowel syndrome and inflammatory bowel disease, with no side effects and high patient tolerance. Formulation 2, which does not contain polydextrose and oat β-glucan, is less effective, and formulation 3, which does not contain resistant dextrin and yeast β-glucan but contains fructooligosaccharides and inulin, may even cause side effects in patients. This further illustrates the synergistic effect between the components of the composition of this application and the safety of the composition.

[0124] Example 4.

[0125] To investigate the effects of a prebiotic formulation composed of nine ingredients—resistant dextrin, PHGG, polydextrose, oat β-glucan, yeast β-glucan, gum arabic, resistant starch, pectin, and rhamnose—we studied the effects of administering different prebiotic formulations to patients.

[0126] Patient information: A middle-aged woman with chronic constipation, having a bowel movement once every 3-4 days, significant abdominal distension, and occasional abdominal pain.

[0127] (1) Treatment Formula 1: a. Resistant dextrin: 50 parts by weight b. PHGG: 10 parts by weight c. Polydextrose: 15 parts by weight d. Oat beta-glucan: 5 parts by weight e. Yeast β-glucan: 5 parts by weight f. Gum arabic: 15 parts by weight g. Resistant starch: 20 parts by weight h. Pectin: 10 parts by weight i. Rhamnose: 10 parts by weight (2) Treatment Formula 2 (without yeast beta-glucan and resistant starch): a. Resistant dextrin: 50 parts by weight b. PHGG: 10 parts by weight c. Polydextrose: 15 parts by weight d. Oat beta-glucan: 5 parts by weight e. Gum arabic: 15 parts by weight f. Pectin: 10 parts by weight g. Rhamnose: 10 parts by weight (3) Treatment Formula 3 (containing inulin and fructooligosaccharides, but without yeast beta-glucan and resistant starch): a. Resistant dextrin: 50 parts by weight b. PHGG: 10 parts by weight c. Polydextrose: 15 parts by weight d. Oat beta-glucan: 5 parts by weight e. Gum arabic: 15 parts by weight f. Pectin: 10 parts by weight g. Rhamnose: 10 parts by weight h. Inulin: 20 parts by weight i. Fructooligosaccharides: 5 parts by weight (4) Preparation method: Mix all the ingredients and place them in a bag.

[0128] (5) Effects of use: Treatment Formula 1: After taking it continuously for 7 days, the frequency of bowel movements will increase to once a day, the stool will be formed, and there will be no abdominal distension or pain, making the bowel movement process easy.

[0129] Treatment Formula 2: After taking the medicine, bowel movements become more frequent and smoother than before taking it. The stool remains formed, the bowel movement process is easy, and there may be occasional bloating and abdominal pain.

[0130] Treatment Formula 3: After taking it, bowel movements become smooth and stools become formed, but bloating and occasional abdominal pain may occur.

[0131] The results are shown in Table 3.

[0132] Table 3. Patient Information

[0133] The above results demonstrate that the composition of this application effectively improves symptoms such as bloating, diarrhea, and abdominal pain caused by irritable bowel syndrome and inflammatory bowel disease, with no side effects and high patient tolerance. Formulation 2, which does not contain yeast β-glucan and resistant starch, is less effective, while formulation 3, which does not contain yeast β-glucan and resistant starch but contains fructooligosaccharides and inulin, may even cause side effects in patients. This further illustrates the synergistic effect between the components of the composition of this application, as well as the safety of the composition.

[0134] Example 5.

[0135] To investigate the effects of a prebiotic formulation composed of nine ingredients—resistant dextrin, PHGG, polydextrose, oat β-glucan, yeast β-glucan, gum arabic, resistant starch, pectin, and rhamnose—we studied the effects of administering different prebiotic formulations to patients.

[0136] Patient information: A young IBS patient who experiences diarrhea 1-2 times a day, and often has symptoms such as abdominal distension, abdominal pain, and excessive flatulence after meals.

[0137] (1) Treatment Formula 1: a. Resistant dextrin: 30 parts by weight b. PHGG: 30 parts by weight c. Polydextrose: 10 parts by weight d. Oat beta-glucan: 15 parts by weight e. Yeast β-glucan: 10 parts by weight f. Gum arabic: 40 parts by weight g. Resistant starch: 10 parts by weight h. Pectin: 10 parts by weight i. Rhamnose: 15 parts by weight (2) Treatment Formula 2 (without yeast beta-glucan and gum arabic): a. Resistant dextrin: 30 parts by weight b. PHGG: 30 parts by weight c. Polydextrose: 10 parts by weight d. Oat beta-glucan: 15 parts by weight e. Resistant starch: 10 parts by weight f. Pectin: 10 parts by weight g. Rhamnose: 15 parts by weight (3) Treatment Formula 3 (containing no yeast β-glucan and gum arabic, but containing fructooligosaccharides and inulin): a. Resistant dextrin: 30 parts by weight b. PHGG: 30 parts by weight c. Polydextrose: 10 parts by weight d. Oat beta-glucan: 15 parts by weight e. Resistant starch: 10 parts by weight f. Pectin: 10 parts by weight g. Rhamnose: 15 parts by weight h. Inulin: 40 parts by weight i. Fructooligosaccharides: 10 parts by weight (4) Preparation method: After being mixed evenly, it is made into powder and then packaged in small bags.

[0138] (5) Effects of use: Treatment Formula 1: After about 10 days of use, bowel movements will basically return to normal, and symptoms such as abdominal distension, abdominal pain, and excessive flatulence after meals will be significantly reduced.

[0139] Treatment Formula 2: After 10 days of use, bowel movements improved compared to before, but not as well as Formula 1. Symptoms such as postprandial bloating, abdominal pain, and excessive flatulence were not as well improved as with Formula 1.

[0140] Treatment Formula 3: After use, there was no significant improvement in bowel movements, and symptoms even increased after meals.

[0141] The results are shown in Table 4.

[0142] Table 4. Patient Information

[0143] The above results demonstrate that the composition of this application effectively improves symptoms such as bloating, abdominal pain, and abnormal intestinal fermentation caused by irritable bowel syndrome and inflammatory bowel disease, with no side effects and high patient tolerance. Formulation 2, which does not contain yeast β-glucan and gum arabic, is even worse; formulation 3, which does not contain either yeast β-glucan or gum arabic but contains fructooligosaccharides and inulin, may even cause side effects in patients. This further illustrates the synergistic effect between the components of the composition of this application, as well as the safety of the composition.

[0144] Example 6.

[0145] Furthermore, we have demonstrated the effectiveness of the following probiotic formulations in treating IBS and IBD-related symptoms.

[0146] Formula 1.

[0147] (1) Formulation composition (parts by weight): 30 parts by weight of resistant dextrin; 20 parts by weight of PHGG (partially hydrolyzed guar gum, galactomannan); 15 parts by weight of polydextrose; 10 parts by weight of oat β-glucan; 5 parts by weight of yeast β-glucan; 15 parts by weight of gum arabic; 20 parts by weight of resistant starch; 15 parts by weight of pectin; 10 parts by weight of rhamnose.

[0148] (2) Preparation method: a. Weigh the raw materials according to the specified proportions; b. Mix the raw materials evenly under low temperature conditions and package them to obtain prebiotic compound powder.

[0149] Formula 2.

[0150] (1) Formula composition (parts by weight): 25 parts by weight of resistant dextrin; 15 parts by weight of PHGG (partially hydrolyzed guar gum, galactomannan); 10 parts by weight of polydextrose; 8 parts by weight of oat β-glucan; 5 parts by weight of yeast β-glucan; 300 parts by weight of purified water.

[0151] (2) Preparation method: a. Weigh the raw materials according to the specified proportions; b. Use a high-speed shear homogenizer to fully dissolve all raw materials in pure water; c. Low-temperature instantaneous sterilization (temperature ≤ 65℃, sterilization time 15 seconds) is used to ensure the stability of active ingredients; d. Using aseptic filling technology, ready-to-drink prebiotic beverages are prepared.

[0152] Formula 3.

[0153] (1) Formulation composition (parts by weight): 40 parts by weight of resistant dextrin; 20 parts by weight of PHGG (partially hydrolyzed guar gum, galactomannan); 10 parts by weight of polydextrose; 10 parts by weight of oat β-glucan; 5 parts by weight of yeast β-glucan.

[0154] (2) Preparation method: a. Weigh the raw materials according to the specified proportions; b. A low-temperature mixing process is used to ensure that all raw materials are mixed evenly; c. Particles are prepared by spray drying, with the spray temperature controlled at ≤ 50℃; d. Fluidized bed granulation process is adopted to ensure uniform particle formation and control the particle size between 0.5-1.5mm; e. Packaging yields prebiotic granules.

[0155] Formula 4.

[0156] (1) Formulation composition (parts by weight): 35 parts by weight of resistant dextrin; 25 parts by weight of PHGG (partially hydrolyzed guar gum, galactomannan); 15 parts by weight of polydextrose; 10 parts by weight of oat β-glucan; 5 parts by weight of yeast β-glucan.

[0157] (2) Preparation method: a. Weigh the raw materials according to the specified proportions; b. Low-temperature mixing technology is used to ensure that all raw materials are mixed evenly; c. Spray drying process is used to maintain the powder's good flowability and instant solubility; d. Packaging yields prebiotic instant powder.

[0158] Formula 5.

[0159] (1) Formulation composition (parts by weight): 35 parts by weight of resistant dextrin; 25 parts by weight of PHGG (partially hydrolyzed guar gum, galactomannan); 15 parts by weight of polydextrose.

[0160] (2) Preparation method: a. Weigh the raw materials according to the specified proportions; b. Low-temperature mixing technology is used to ensure that all raw materials are mixed evenly; c. Spray drying process is used to maintain the powder's good flowability and instant solubility; d. Packaged into prebiotic instant powder. This prebiotic formula is highly water-soluble and has minimal impact on the taste and flavor of coffee, tea, or other beverages, making it particularly suitable for use in these drinks.

[0161] Example 7.

[0162] 1 Experimental Design

[0163] 1.1 Experimental Materials: Sodium dextran sulfate (MP Biomedicals, molecular weight, 36,000 to 50,000 Da, Cat. No. 9011-18-1), resistant dextrin, oat beta-glucan, yeast beta-glucan, partially hydrolyzed guar gum (PHGG) and polydextrose, Bifidobacterium adolescentis (… Bifidobacterium adolescents is ATCC 15703) and Lactobacillus reuteri ( Lactobacillus reuteri (ATCC 23272).

[0164] 1.2 Experimental Grouping

[0165] Male C57 BL / 6 mice (6 weeks old, 20 ± 2 g) were randomly divided into the following 4 groups, with 11 mice in each group: Control group (no induction, no intervention); Model group (DSS model induced, no intervention); Prebiotics group (DSS model induced, prebiotics administered); Synbiotics group (DSS model induced, synbiotics administered).

[0166] 1.3 Mouse model of ulcerative colitis (IBD)

[0167] The model group mice were given 2% dextran sodium sulfate (DSS) in their drinking water and intermittently consumed 2% DSS (molecular weight: 36-50 kDa) water for one week using a three-cycle intermittent method. After one week, they were fed normal water for two weeks, for a total of 60 days, to establish the UC model. Figure 1 ).

[0168] 1.4 Prebiotic Intervention

[0169] Resistant dextrin, oat β-glucan, yeast β-glucan, partially hydrolyzed guar gum (PHGG), and polydextrose were mixed at weight ratios of 25%, 15%, 15%, 25%, and 20%, respectively, and dissolved in PBS. Based on the maximum acceptable daily prebiotic intake of 20 g for a 70 kg adult, the recommended intake of compound prebiotics in mice was determined to be 300 mg / kg daily. Mice in the prebiotic group were administered the prebiotic via gavage daily at a volume of 400 μL.

[0170] 1.5 Probiotic Intervention

[0171] Bifidobacterium adolescentis and Lactobacillus reuteri were cultured in MRS broth (Oxoid, CM1175B) under anaerobic conditions at 37°C. Bifidobacterium adolescentis and Lactobacillus reuteri were added to the above prebiotic formula at a 1:1 ratio, totaling 1 x 10⁻⁶. 9 CFU was administered to mice in the Synbiotic group by gavage daily at a volume of 400 uL.

[0172] 1.6 Evaluation Indicators

[0173] Observe the general condition and defecation changes of the mice, and weigh them daily. On day 60, sacrifice the mice, weigh their spleens, and measure the length of their colons. Collect mouse serum for metabolomics analysis.

[0174] 2. Experimental Results

[0175] 2.1 Mortality rate

[0176] like Figure 2 As shown, no mice died in the control group and the synbiotic group, while 3 mice died in the model group on days 6 and 12, and 1 mouse died in the prebiotic group on day 57. The lifespan of the model mice treated with prebiotics and synbiotics was significantly prolonged.

[0177] Conclusion: Both the prebiotics and synbiotics in this patented study can significantly reduce the mortality rate in a mouse model of inflammatory bowel disease.

[0178] 2.2 Weight

[0179] like Figure 3 As shown, compared with the control group, the model group had a significant decrease in body weight (29.46 vs 23.08, p ≤0.0001), indicating successful model establishment. Compared with the model group, mice treated with prebiotics or synbiotics daily showed a rebound in body weight. Moreover, the effect of synbiotics was more significant (synbiotics: 23.08 vs 25.79, p = 0.0007).

[0180] Conclusion: Both the prebiotics and synbiotics in this patent can increase the body weight of the inflammatory bowel disease mouse model, and the synbiotics have a particularly significant effect on increasing the body weight of the inflammatory bowel disease mouse model.

[0181] 2.3 Spleen weight

[0182] In inflammatory bowel disease, spleen weight is closely related to the level of inflammation. Elevated spleen weight suggests overactivation of the immune system. Figure 4 As shown, compared with the control group, the spleen weight of the model group was significantly increased (0.08416 vs 0.1687, p = <0.0001), indicating successful model establishment. Compared with the model group, the spleen weight of mice treated with daily prebiotics or synbiotics was significantly reduced (prebiotics: 0.1687 vs 0.1149, p = 0.0017; synbiotics: 0.1687 vs 0.1186, p = 0.0037), indicating a decrease in inflammation levels.

[0183] Conclusion: Both the prebiotics and synbiotics in this patented study can significantly reduce overall inflammation in a mouse model of inflammatory bowel disease.

[0184] 2.4 Colon length

[0185] In inflammatory bowel disease, the degree of shortening of the colon is significantly negatively correlated with the level of inflammation; that is, the shorter the colon, the more severe the inflammation.

[0186] The results are as follows Figure 5 As shown, compared with the control group, the colon length in the model group was significantly shortened (6.810 vs 5.071, p = <0.0001), indicating successful model establishment. Compared with the model group, mice treated with prebiotics or synbiotics daily had significantly longer colons (prebiotics: 5.071 vs 5.864, p = 0.0371; synbiotics: 5.071 vs 6.300, p = 0.0006).

[0187] Conclusion: Both the prebiotics and synbiotics in this application can significantly reduce overall inflammation in a mouse model of inflammatory bowel disease.

[0188] 2.5 Serum metabolites

[0189] The short-chain fatty acids involved in this experiment include: acetic acid; butyric acid; valeric acid; ethylmethylacetic acid (common name: 2-methylbutyric acid); isobutyric acid; isovaleric acid; propionic acid; caproic acid; and isocaproic acid.

[0190] 2.5.1 Prebiotics

[0191] The results are as follows Figure 6 As shown, compared with the model group, the levels of short-chain fatty acids in the blood of mice in the prebiotic group were increased. For example, the levels of acetic acid (93.54 vs 122.7, p = 0.0225), butyric acid (2.460 vs 3.319, p = 0.0348), and valerate (0.5361 vs 0.6044, p = 0.0494) were significantly increased, and the levels of other short-chain fatty acids were also increased.

[0192] 2.5.2 Biostime

[0193] The results are as follows Figure 7 As shown, compared with the model group, the levels of short-chain fatty acids in the blood of mice in the synbiotic group were increased. For example, the acetic acid content was significantly increased (93.54 vs 115.2, p = 0.0342), and the levels of other short-chain fatty acid components were also slightly increased.

[0194] 2.6 Gut microbiota metagenomic sequencing analysis

[0195] 2.6.1 Prebiotics

[0196] The results are as follows Figure 8 and Figure 9 As shown, the intragroup diversity in the prebiotic group was significantly higher than that in the model group (Chao1, p = 0.015). Data indicates that after prebiotic intervention, the number of species (richness) of the gut microbiota in mice was higher than that in the diseased model group; however, the difference between the two groups was not significant (PERMANOVA [Permutational multivariate analysis of variance], p = 0.123). This may suggest that the role of prebiotics is more about enriching the diversity of gut microbiota than reshaping its structure.

[0197] 2.6.2 Biostime

[0198] The results are as follows Figure 10 and Figure 11 As shown, the intragroup diversity in the synbiotic group was not significantly different from that in the model group, but the intergroup diversity between the synbiotic group and the model group was significant (PERMANOVA, p = 0.044), indicating that synbiotic intervention significantly altered the gut microbiota structure. The following gut microbiota were significantly enriched in the synbiotic group ( Figure 12 ): (1) Paramuribaculum intestinale / Paramuribaculum: a mucosa-associated bacterium, whose growth may be improved by synbiotics.

[0199] (2) Bacteroides include: Bacteroides uniformis, B. humanifascis, B. nordii, B. heicogenes, B. eggerthii, B. stercoris, B. zoogleoformans, B. heparinolyticus, etc. As the core bacterial group, their abundance increased after synbiotic intervention, indicating that synbiotics provided sufficient "food" (prebiotics) for these polysaccharide-degrading probiotics, enabling them to proliferate healthily rather than become pathogenic.

[0200] (3) Alistipes includes: Alistipes shahii, A. dispar, A. onderdonkii, A. senegalensis, A. finegoldii, A. megaguti, A. communis, etc.: an important family and genus under the phylum Bacteroidetes. Most Alistipes species are positively correlated with disease states such as inflammatory bowel disease (IBD), depression, and cancer, but their specific mechanisms of action are complex, including potential pathogenicity and possible involvement in bile acid metabolism. Based on the results of other embodiments (e.g., increased colon length and elevated SCFA levels), Alistipes may play a positive role. The enrichment of Alistipes may be part of synbiotic regulation of the overall structure and function of the gut microbiota, and its specific role may be intertwined with other microbiota members and the physiological state of the host.

[0201] In summary, the prebiotics and synbiotics of this application can effectively treat and alleviate inflammatory bowel disease (IBD), and are well tolerated by subjects. The prebiotics and synbiotics of this application cover the distal colon and contain a variety of different components. Their different metabolites can benefit a wider range of bacterial species, thereby promoting the balanced growth of the gut microbiota, significantly optimizing the gut microecological environment, and significantly improving the health of subjects. For example, they help subjects maintain a normal weight and steadily increase it; they can reduce the level of inflammation in subjects, such as significantly reducing spleen weight and increasing colon length; they can improve the gut microbiota in subjects, increase the level of short-chain fatty acids (SCFAs), enhance the diversity of the gut microbiota, and increase the level of beneficial bacteria.

[0202] Although specific embodiments of the invention have been described in detail, those skilled in the art will understand that various modifications and variations can be made to the details based on all the published teachings, and all such changes are within the scope of protection of the invention. The entire scope of the invention is given by the appended claims and any equivalents thereof.

Claims

1. A composition comprising the following components: Resistant dextrin, partially hydrolyzed guar gum (PHGG), polydextrose, and β-glucan. Preferably, the β-glucan is selected from oat β-glucan, yeast β-glucan, mushroom β-glucan, algal β-glucan, or any combination thereof.

2. The composition according to claim 1, wherein, by weight, the composition comprises the following components: 10-50 parts of resistant dextrin, 10-40 parts of PHGG, 5-30 parts of polydextrose and 10-45 parts of β-glucan; Preferably, the composition comprises the following components: resistant dextrin, PHGG, polydextrose, oat β-glucan and yeast β-glucan; Preferably, the composition comprises, by weight, the following components: 10-50 parts of resistant dextrin, 10-40 parts of PHGG, 5-30 parts of polydextrin, 5-25 parts of oat β-glucan and 5-20 parts of yeast β-glucan; Preferably, the composition comprises, by weight, the following components: 20-50 parts of resistant dextrin, 10-40 parts of PHGG, 10-20 parts of polydextrin, 5-20 parts of oat β-glucan and 5-10 parts of yeast β-glucan; Preferably, the composition comprises, by weight, the following components: 25-50 parts resistant dextrin, 10-35 parts PHGG, 10-20 parts polydextrose, 5-15 parts oat β-glucan and 5-10 parts yeast β-glucan.

3. The composition according to claim 1 or 2, wherein, by weight, the composition further comprises: Gum arabic, resistant starch, pectin, and rhamnose; Preferably, the composition comprises, by weight, the following components: 25-50 parts resistant dextrin, 10-35 parts PHGG, 10-20 parts polydextrose, 5-15 parts oat β-glucan, 5-10 parts yeast β-glucan, 10-50 parts gum arabic, 5-50 parts resistant starch, 10-30 parts pectin, and 5-30 parts rhamnose; Preferably, the composition comprises, by weight, the following components: 25-50 parts resistant dextrin, 10-35 parts PHGG, 10-20 parts polydextrose, 5-15 parts oat β-glucan, 5-10 parts yeast β-glucan, 10-40 parts gum arabic, 10-20 parts resistant starch, 5-15 parts pectin, and 10-20 parts rhamnose; Preferably, the composition comprises, by weight, the following components: 25-50 parts resistant dextrin, 10-35 parts PHGG, 10-20 parts polydextrose, 5-15 parts oat β-glucan, 5-10 parts yeast β-glucan, 15-40 parts gum arabic, 10-20 parts resistant starch, 5-15 parts pectin (e.g., 10 parts), and 10-15 parts rhamnose.

4. The composition according to any one of claims 1-3, wherein, by weight, the composition comprises or consists of the following components: (1) Resistant dextrin, PHGG, polydextrose, oat β-glucan and yeast β-glucan; or (2) Resistant dextrin, PHGG, polydextrose, oat β-glucan, yeast β-glucan, gum arabic, resistant starch, pectin and rhamnose; Preferably, the composition does not contain inulin and / or fructooligosaccharides.

5. A synbiotic composition comprising the composition according to any one of claims 1-4, and probiotics; Preferably, the probiotics are selected from bacteria, fungi (e.g., yeast), or any combination thereof; Preferably, the probiotics are selected from Lactobacillus, Bifidobacterium, Bacillus, Propionibacterium, Streptococcus, Lactococcus, Pediococcus, Enterococcus, Staphylococcus, or any combination thereof; Preferably, the probiotic is Bifidobacterium adolescentis (Bifidobacterium adolescentis). Bifidobacterium adolescentis ) and Lactobacillus reuteri ( Lactobacillus reuteri ); Preferably, the ratio of Bifidobacterium adolescentis to Lactobacillus reuteri is 1:3 to 3:1 (e.g., 1:3 to 1:2, 1:2 to 1:1, 1:1 to 2:1, 2:1 to 3:1). Preferably, the probiotics are in a concentration of 10... 6 Up to 10 12 The amount of CFU / dose present; Preferably, the synbiotic composition comprises resistant dextrin, PHGG, polydextrose, oat β-glucan, yeast β-glucan, Bifidobacterium adolescentis, and Lactobacillus reuteri; Preferably, the resistant dextrin, PHGG, polydextrose, oat β-glucan and yeast β-glucan in the synbiotic composition are 15-35 parts, 15-35 parts, 10-30 parts, 5-25 parts and 5-25 parts respectively, calculated by weight.

6. A postbiotic composition comprising the composition according to any one of claims 1-4, and probiotics, components of probiotics, and / or metabolites of probiotics; Preferably, the probiotics are selected from bacteria, fungi (e.g., yeast), or any combination thereof; Preferably, the probiotics are selected from Lactobacillus, Bifidobacterium, Bacillus, Propionibacterium, Streptococcus, Lactococcus, Pediococcus, Enterococcus, Staphylococcus, or any combination thereof; Preferably, the probiotic is Bifidobacterium adolescentis (Bifidobacterium adolescentis). Bifidobacterium adolescentis ) and Lactobacillus reuteri ( Lactobacillus reuteri ); Preferably, the ratio of Bifidobacterium adolescentis to Lactobacillus reuteri is 1:3 to 3:1 (e.g., 1:3 to 1:2, 1:2 to 1:1, 1:1 to 2:1, 2:1 to 3:1).

7. A pharmaceutical composition comprising the composition according to any one of claims 1-4, the synbiotic composition according to claim 5, or the postbiotic composition according to claim 6; Preferably, the pharmaceutical composition further includes additional active ingredients; Preferably, the additional active ingredient is capable of treating and / or improving the subject's intestinal disease; Preferably, the intestinal disease is selected from diseases and / or symptoms associated with irritable bowel syndrome (IBS) and / or inflammatory bowel disease (IBD); Preferably, the disease is selected from Crohn's disease, ulcerative colitis, primary sclerosing cholangitis (PSC), erythema nodosum, pyoderma gangrenosa, uveitis, scleritis, peripheral or axial spondyloarthritis, venous thromboembolism, colorectal cancer, or any combination thereof; Preferably, the symptoms are selected from abdominal pain, abdominal distension, urgency to defecate, constipation, diarrhea, weight loss, perianal lesions, growth retardation, or any combination thereof; Preferably, the pharmaceutical composition further includes a pharmaceutically acceptable carrier and / or excipient; Preferably, the pharmaceutical composition is in the form of a solution, suspension, powder, tablet, pill, emulsion, gel, capsule, granule, elixir, lozenge, suppository, injection, inhaler, or spray.

8. A dietary supplement comprising the composition of any one of claims 1-4, the synbiotic composition of claim 5, the postbiotic composition of claim 6, or the pharmaceutical composition of claim 7; Preferably, the dietary supplement further includes additional excipients; Preferably, the additional excipients are selected from food additives, food processing aids, nutritional fortifiers, or any combination thereof; Preferably, the food additive is selected from sweeteners, acidity regulators, food flavorings, or any combination thereof; Preferably, the additional excipients are selected from: honey, xylitol, erythritol, citric acid, DL-malic acid, maltodextrin, vitamin C, vitamin E, calcium, iron, zinc, or any combination thereof; Preferably, the dietary supplement is selected from dried foods, pressed foods, puffed foods, and baked foods; Preferably, the dietary supplement is selected from solid beverages (e.g., solid beverage powder, solid beverage granules), freeze-dried blocks, freeze-dried powder, candy, or liquid beverages (e.g., ready-to-drink juice, concentrated juice).

9. A method for preparing a composition according to any one of claims 1-4, a synbiotic composition according to claim 5, a postbiotic composition according to claim 6, a pharmaceutical composition according to claim 7, or a dietary supplement according to claim 8, comprising: Provide each component of the composition according to any one of claims 1-4; Preferably, the method further includes: dissolving each component of the composition in a solvent (e.g., water); Preferably, the method further includes: preparing the composition into granules or powder (e.g., by spray drying).

10. Use of the composition of any one of claims 1-4, the synbiotic composition of claim 5, the postbiotic composition of claim 6, the pharmaceutical composition of claim 7, or the dietary supplement of claim 8 in the preparation of a medicament for the treatment and / or improvement of intestinal diseases in a subject; Preferably, the intestinal disease is selected from diseases and / or symptoms associated with irritable bowel syndrome (IBS) and / or inflammatory bowel disease (IBD); Preferably, the disease is selected from Crohn's disease, ulcerative colitis, primary sclerosing cholangitis (PSC), erythema nodosum, pyoderma gangrenosa, uveitis, scleritis, peripheral or axial spondyloarthritis, venous thromboembolism, colorectal cancer, or any combination thereof; Preferably, the symptoms are selected from abdominal pain, abdominal distension, urgency to defecate, constipation, diarrhea, weight loss, perianal lesions, mood disorders, growth retardation, or any combination thereof; Preferably, the subject is a mammal; Preferably, the mammal is selected from rats, pigs, rabbits, monkeys, sheep, and humans.

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