Nutraceutical formulations for prevention and amelioration of inflammatory bowel disease (IBD)

Abstract

The present invention relates to nutraceutical formulations for the prevention and dietary management of inflammatory bowel disease (IBD), including conditions such as colitis and ulcerative colitis. The formulations comprise fructooligosaccharide (FOS), an amino acid– organic acid blend containing arginine, glycine, and citric acid (UT 18), and enhancer protein(EP), optionally in combination, in a physiologically acceptable carrier. The compositions are intended for oral administration to support gastrointestinal health, maintain normal intestinal barrier function, and promote a balanced gut microbiota. Preclinical evaluation in DSSchallenged animal models demonstrated improved gut health parameters, maintenance of body weight, reduced disease activity scores, and preservation of colon morphology. These synergistic combinations of bioactive dietary ingredients are non-toxic, derived from natural sources, and suitable for incorporation into functional foods, dietary supplements, or nutraceutical beverages. The invention provides a safe, effective, and sustainable approach for promoting digestive wellbeing and reducing the risk or severity of colitis, IBD, IBS, gastritis and other intestinal discomfort through regular dietary inclusion.

Description

[0001] NUTRACEUTICAL FORMULATIONS FOR PREVENTION AND AMELIORATION OF INFLAMMATORY BOWEL DISEASE (IBD)

[0002] FIELD OF INVENTION

[0003] The present invention belongs to the field of nutraceuticals, functional foods, and gastrointestinal therapeutics, specifically targeting the treatment and prevention of inflammatory bowel diseases (IBD) such as ulcerative colitis and colitis. The disclosed invention focuses on functional nutrition formulations driven by synthetic biology, combining prebiotics, metabolic enhancers, bioactive compounds, and stem cell chemoattractants. These formulations are designed to support gut health, enhance metabolic efficiency, promote tissue regeneration, and extend cellular longevity. By integrating scientifically backed ingredients such as fructooligosaccharides (FOS) for microbiome modulation, UT 18 for cellular energy and stem cell attraction, and brazzein for metabolic support, the invention offers a holistic approach to health optimization. Additionally, vitamin K contributes to bone and cardiovascular health, while enhancer protein enhances regenerative potential by maintaining telomere length. Optional Ayurvedic bioactives like ashwagandha, shilajit, and curcumin provide further benefits, including stress reduction, energy enhancement, and anti-inflammatory effects. The formulations are structured progressively, building on each other to amplify benefits. They can be delivered in various formats, including oral drinks, gummy tablets, and traditional capsules, ensuring accessibility and convenience. By leveraging advances in synthetic biology and nutrition science, this invention presents an innovative solution for improving overall well-being through targeted functional nutrition.

[0004] BACKGROUND OF THE INVENTION

[0005] Ulcerative colitis and Crohn’s disease are chronic inflammatory conditions with a significant impact on quality of life. Current treatments involve immunosuppressants and biologics, which may have adverse effects and limited long-term safety. Nutraceuticals like prebiotics and natural bioactives offer promising therapeutic alternatives.The disclosed formulations propose a comprehensive approach to enhancing various aspects of health, particularly focusing on gut microbiome balance and related functions. A balanced gut microbiome, or gut microbiota, refers to a diverse and thriving community of microorganisms (bacteria, fungi, and viruses) in the gut, essential for digestion, immunity, and overall health.

[0006] Maintaining this balance involves a diverse diet, mindful antibiotic use, and a healthy lifestyle.

[0007] Disclosed below is a breakdown of the components and potential applications of these formulations:

[0008] Gut Microbiome Balance: An imbalance in the gut microbiome, known as dysbiosis, can lead to various health problems, including digestive issues, inflammation, and even metabolic disorders. Dysbiosis can impair nutrient absorption, regulate blood sugar, and even impact mental health. Probiotics and prebiotics formulations could contain live beneficial bacteria (probiotics) and substances that promote their growth (prebiotics), which help maintain a healthy gut environment, supporting digestion and absorption of nutrients.

[0009] Stem Cell Homing and Differentiation: Stem cell homing refers to the directed migration of stem cells to a specific location or "niche" where they can proliferate and differentiate, while stem cell differentiation is the process where stem cells become specialized cell types. Homing is the process by which circulating stem cells (endogenous or exogenous) find and enter their corresponding environmental niche, which is crucial for tissue repair and regeneration. Factors promoting stem cell activity that enhance the ability of stem cells to migrate to sites of injury and differentiate into necessary cell types can promote regeneration in tissues, particularly in the gut and oral cavity.

[0010] Metabolic Function: Metabolism is the process by which the body uses energy from food to perform vital functions. It's a continuous process that happens even during sleep or rest. Metabolic pathways include carbohydrate metabolism (biochemical processes that break down, form, and interconvert carbohydrates in living organisms), lipid metabolism (an important metabolic activity that produces metabolites that regulate gene expression and activate immune checkpoints), and glucose metabolism (a pivotal component in human metabolic processes). Nutraceuticals enhance metabolicpathways that may improve energy utilization and storage, helping in health conditions like obesity or metabolic syndromes.

[0011] Immune Response Enhancement: The immune response is the body's defense mechanism against harmful substances, such as bacteria and viruses. It involves the recognition, attack, and destruction of antigens on the surface of these substances. Immunomodulatory ingredients are beneficial compounds that help modulate the immune system, potentially reducing inflammation and enhancing the body's response to pathogens or damage.

[0012] The formulations which constitute the present invention help address a variety of health issues, including:

[0013] Oral and Gut Diseases: The "oral-gut axis" refers to the interconnectedness of the oral and gut microbiomes, where oral bacteria can translocate to the gut and influence gut health, potentially contributing to various gastrointestinal and systemic diseases.

[0014] Gingivitis: Gingivitis, the earliest stage of gum disease, is an inflammation of the gums caused by bacterial plaque buildup, leading to symptoms like red, swollen, and bleeding gums. If left untreated, it can progress to a more severe form, periodontitis, which can cause bone loss and tooth loss. The disclosed formulations can reduce inflammation and promote oral health.

[0015] Colitis and IBD (Inflammatory Bowel Disease): Inflammatory Bowel Disease (IBD) encompasses chronic inflammatory conditions of the digestive tract, with the two main types being Crohn's disease and ulcerative colitis, both of which can cause inflammation and ulcers.

[0016] Disclosed formulations can help in restoring gut flora and reducing inflammatory responses.

[0017] IBS (Irritable Bowel Syndrome): Irritable Bowel Syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain and changes in bowel habits, often including diarrhea, constipation, or both, without any visible damage to the digestive tract.

[0018] Disclosed formulations provide relief by normalizing gut function.Radiation-Induced Mouth Ulcers: Radiotherapy, especially for head and neck cancers, can cause mouth ulcers (oral mucositis) as a side effect, leading to a sore mouth and difficulty eating and swallowing. Disclosed formulations promote healing and reduce side effects from treatments such as radiation therapy.

[0019] Surgical Recovery: GI (Gastrointestinal) and oral cancer surgery involves removing cancerous tissue and potentially reconstructive procedures, with options including wide local excision, neck dissection, and specialized techniques like maxillectomy or robotic surgery, depending on the cancer's location and stage. Disclosed formulations can aid in recovery and tissue regeneration after surgical procedures.

[0020] Bone and Joint Health:

[0021] Osteoarthritis Support: Osteoarthritis (OA), the most common type of arthritis, is a degenerative joint disease where cartilage breaks down, causing pain, stiffness, and reduced mobility, often affecting the hands, knees, hips, and spine. Disclosed formulations can promote cartilage health and reduce pain and inflammation.

[0022] General Bone Health: Bone health refers to the overall condition and strength of the skeletal system, crucial for mobility, preventing fractures, and maintaining overall well-being, influenced by factors like genetics, nutrition, physical activity, and hormonal balance. Disclosed formulations can provide nutrients essential for bone density and repair.

[0023] Cardiovascular Support: Cardiovascular health, encompassing the heart and blood vessels, is crucial for overall well-being. Maintaining a healthy lifestyle, including a balanced diet, regular exercise, and managing stress, can significantly reduce the risk of cardiovascular diseases. Disclosed formulations can be helpful in promoting heart health, potentially reducing risks associated with cardiovascular disease.Longevity Enhancement: Longevity enhancement focuses on strategies to live longer and healthier lives, encompassing lifestyle choices, medical interventions, and emerging scientific advancements, aiming to extend lifespan and improve the quality of life during those years.

[0024] Disclosed formulations supports overall health and vitality, through antioxidant effects and promoting cellular health.

[0025] The formulations that constitute the disclosed invention represent a novel approach to regenerative therapy by targeting multiple systems in the body through the gut microbiome, immune modulation, and cellular regeneration. This multifaceted strategy could offer significant benefits for individuals suffering from a variety of health issues, particularly those related to the gut and oral health.

[0026] The disclosed invention represents a new evolution in the nutraceutical field, moving from traditional formulations focused on isolated bioactive compounds to complex, synergistic approaches that leverage advances in various scientific disciplines.

[0027] Evolution of Nutraceutical Formulations

[0028] 1. Single Bioactive Compounds: Traditional nutraceuticals often emphasize isolated compounds, such as vitamins, minerals, or specific plant extracts, targeting well-defined health concerns (e.g., omega-3 fatty acids for heart health, glucosamine for joint health). While effective in certain scenarios, these approaches sometimes fall short of addressing complex, multifactorial conditions.

[0029] 2. Synergistic Pathways: Recent research underscores the importance of synergy. Instead of focusing solely on isolates, formulators are now considering how various compounds can work together to enhance overall health outcomes. This is important because biological systems are inherently complex, with numerous interactions occurring at cellular and metabolic levels.

[0030] Advances in Relevant Scientific Fields

[0031] 1. Synthetic Biology: Synthetic biology enables the engineering of microorganisms and biosystems to produce desired bioactive compounds or enhance their effectiveness. For instance,engineered probiotics can be developed to deliver specific therapeutic agents, modulate inflammation, or support gut health.

[0032] 2. Microbiome Science: Understanding the human microbiome — the collection of microorganisms living in and on our bodies — has transformed the field of health. The microbiome plays a crucial role in digestion, immune function, and even mental health. Advances in this field allow for the formulation of prebiotics and probiotics that not only support gut health but also influence systemic health by affecting the immune response and metabolic processes.

[0033] 3. Regenerative Medicine: Research in regenerative medicine focuses on harnessing the body’s own healing mechanisms, including stem cell activation and differentiation. Nutraceuticals can be designed to support these processes by:

[0034] - Enhancing stem cell homing to sites of injury.

[0035] - Promoting differentiation into specific cell lineages.

[0036] - Modulating the microenvironment to facilitate healing and regeneration.

[0037] Impact on Health

[0038] 1. Stem Cell Activity: Certain natural compounds, such as flavonoids and polyphenols, have been shown to influence stem cell proliferation and differentiation. By combining these compounds with prebiotics and bioactive nutrients, formulations can be optimized to promote tissue repair and regeneration more effectively.

[0039] 2. Metabolic Homeostasis: Nutraceuticals that adjust or support metabolic pathways can help in managing conditions like obesity, diabetes, and metabolic syndrome. This involves enhancing the body’s ability to regulate glucose levels, lipid metabolism, and energy balance.

[0040] 3. Cellular Aging: The aging process is influenced by various factors, including oxidative stress, inflammation, and metabolic decline. Nutraceutical formulations can target these pathways by utilizing antioxidants, anti-inflammatory compounds, and agents that support mitochondrial function, ultimately promoting longevity and health span.Ban et al. in a research paper titled “Nutraceuticals for the Treatment of IBD: Current Progress and Future Directions” (Front Nutr. 2022 Jun 6;9:794169. doi: 10.3389 / fnut.2022.794169), reviewed the research results of dietary fiber, polyphenols, bioactive peptides, and other nutraceuticals in the prevention and treatment of IBD and sought better alternative or supplementary treatment methods for IBD patients.

[0041] The article “Nutraceuticals in the Prevention and Treatment of Inflammatory Bowel Disease” (PMC9207447) offers a detailed exploration of how specific dietary compounds, particularly polyphenols and probiotics, may help manage inflammatory bowel disease (IBD). The review focuses on their individual and combined therapeutic roles, supported by evidence from preclinical and emerging clinical studies.

[0042] Polyphenols, which are bioactive compounds found in plants, have received considerable attention for their anti-inflammatory and antioxidant properties. The article highlights that polyphenolrich fruits, such as strawberries and black raspberries, have shown strong potential in reducing inflammation and the risk of colitis-associated colorectal cancer (CAC). These effects are primarily due to polyphenols' ability to inhibit oxidative stress, inflammatory signaling pathways like NF-κB, and genomic instability in experimental IBD models. Furthermore, polyphenols may also benefit systemic complications of IBD. For instance, the plant-derived polyphenol 7-hydroxy matairesinol has been found to alleviate iron deficiency anemia, a common IBD symptom by downregulating hepcidin, a key iron regulatory hormone.

[0043] A significant challenge with polyphenols is their limited bioavailability. To address this, the review discusses the use of nanotechnology to enhance their absorption and therapeutic impact. Curcumin, when encapsulated in lipid-based nanocarriers, and rosmarinic acid in PEGylated nanoparticles, demonstrated improved anti-inflammatory effects in murine models of colitis. These nanoformulations reduced inflammatory cytokine secretion, neutrophil infiltration, and overall tissue damage in a dose-dependent manner, showing promise as next-generation nutraceutical therapies for IBD.In addition to their standalone effects, polyphenols can act synergistically with probiotics, leading to enhanced therapeutic outcomes. The article highlights an example where blackcurrant, a polyphenol-rich fruit, was fermented with lactic acid bacteria such as Lactobacillus and Streptococcus thermophilus to produce yogurt. This fermentation process not only preserved and enhanced the antioxidant activity of polyphenols but also promoted the growth and viability of beneficial probiotic strains. Such functional foods, combining polyphenols and probiotics, act like synbiotics, offering dual benefits in terms of gut health and inflammation control.

[0044] Probiotics alone also demonstrate notable benefits in IBD treatment. Specific strains, including Lactobacillus plantarum, L. rhamnosus GG, L. paracasei, and Bifidobacterium lactis, have been shown to modulate the immune response by reducing pro-inflammatory cytokines such as TNF-α and IL-6 while boosting anti-inflammatory IL- 10. These effects lead to improved histological outcomes and reduced disease severity in animal models of colitis. Probiotics further help maintain intestinal barrier integrity by upregulating tight junction proteins and promoting mucus production. They inhibit the growth of pathogenic bacteria like E. coli and C. difficile, while simultaneously enhancing the production of beneficial microbial metabolites such as short-chain fatty acids (SCFAs), especially butyrate, which supports mucosal repair and regulates local immune responses.

[0045] More recent innovations involve combining probiotics with polyphenols using nanostructured delivery systems. For instance, one study described in the article involves coating the probiotic E. coli Nissle 1917 with tannic acid and sodium alginate to form a stable nanocomposite. This formulation, named EcN\@SA-pBDT-TA, improved the survival of the probiotic under oxidative stress, increased its retention in the colon, and led to reduced inflammation and better mucosal healing in colitis models. Another study used a coating made from epigallocatechin gallate (EGCG) and chitosan, combined with gold nanozymes, to create a “smart armor” for E.

[0046] coli Nissle, enhancing its therapeutic effects even further.

[0047] The synergy between polyphenols and probiotics is not limited to engineered systems. Functional foods such as polyphenol-rich fermented yogurts offer a natural and practical way to deliver both components together. These combinations enhance the survival of both compounds, reduce inflammation, and support microbial balance, all of which are critical in managing IBD.In conclusion, the article presents strong preclinical evidence supporting the use of polyphenols and probiotics, both individually and in combination — for the treatment and management of IBD. Their mechanisms are complementary: while polyphenols reduce inflammation, oxidative stress, and support microbial diversity, probiotics help restore gut barrier function, regulate immune responses, and produce beneficial metabolites. When used together, especially in innovative delivery formats or functional foods, they offer a compelling, low-toxicity alternative or adjunct to conventional IBD therapies. However, despite these promising results, further clinical trials are necessary to validate their efficacy and optimize formulations for human use.

[0048] In contrast, the present invention proposes a precisely defined, synergistic combination that includes fructooligosaccharide (FOS) at 5–10 % w / v, a specific amino acid–organic acid blend (UT 18) comprising arginine, glycine, and citric acid, together with enhancer protein, all solubilized in phosphate-buffered saline within a nutraceutically acceptable carrier. This formulation is engineered not merely to tap into the known benefits of each component individually, but to achieve demonstrable synergy, as evidenced in DSS-induced colitis animal models by statistically significant reductions in disease activity index, improvements in colon length, and lowered histopathological damage compared to using each component alone.

[0049] The present invention presents a novel nutraceutical composition in which enhancer protein is combined with defined quantities of fructooligosaccharide (5–10 % w / v) and a uniquely formulated amino acid–organic acid blend (UT 18: arginine, glycine, citric acid) within a phosphate-buffered saline carrier. The formulation is specifically engineered to produce a synergistic therapeutic effect beyond the sum of individual components by targeting gut microbiota modulation, suppression of pro-inflammatory cytokines, and promotion of epithelial regeneration. This synergy has been empirically demonstrated in DSS-induced colitis animal models, showing statistically significant reduction in disease activity index, restoration of colon length, and improved histopathology compared to each component alone. The review article referenced above does not disclose a defined combination, nor does it demonstrate synergistic efficacy or explicit applications in colonic inflammation. Thus, the present invention not only introduces a specifically quantified and multicomponent formulation butalso delivers experimentally validated benefits in gastrointestinal inflammation, setting it apart from the broader therapeutic profile as described in the review.

[0050] SUMMARY OF THE INVENTION

[0051] The formulations that constitute the present invention integrate key bioactive ingredients to support gut health, metabolic function, cellular regeneration, and longevity. Each ingredient plays a specific role in enhancing physiological processes.

[0052] Fructooligosaccharides (FOS) serve as prebiotics that promote the growth of beneficial gut bacteria, leading to the production of short-chain fatty acids (SCFAs) with anti-inflammatory properties. UT 18 an amino acid and short chain sugar complex, is believed to enhance cellular energy metabolism and attract stem cells to repair damaged tissues through chemoattraction. Brazzein, a noncaloric sweetener, supports insulin sensitivity and metabolic function, making it beneficial for weight management and blood sugar control. Vitamin K, including KI and K2MK7, is crucial for bone mineralization, cardiovascular health, and stem cell differentiation.

[0053] The formulations are structured progressively, each building upon the previous one to enhance overall benefits. Formula 1 combines FOS, UT 188, and brazzein, forming a foundation that supports gut microbiome balance, metabolic function, and stem cell chemoattraction. Formula 2 builds upon this by adding vitamin K, which enhances bone strength, cardiovascular wellness, and hormonal balance while continuing to promote stem cell differentiation. Formula 3

[0054] completes the sequence by incorporating and enhancer protein, which extends longevity support and enhances regenerative potential by maintaining cellular health and telomere integrity.

[0055] Additionally, optional Ayurvedic bioactives can be incorporated to further enhance the formulations. Ashwagandha, known for its adaptogenic properties, aids in stress reduction and vitality. Shilajit, a traditional energy enhancer, may support cognitive function and nutrient absorption. Curcumin, widely recognized for its anti-inflammatory and antioxidant effects, can help mitigate chronic inflammation and oxidative stress.To ensure accessibility and consumer convenience, these formulations can be offered in various delivery forms. An oral drink provides quick absorption and ease of consumption. Gummy tablets offer an appealing alternative for those who prefer a chewable option with a pleasant taste. Traditional solid dosage forms, such as capsules or tablets, provide a familiar and reliable method of supplementation.

[0056] Together, these formulations create a holistic approach to enhancing gut health, metabolic function, regeneration, and longevity, catering to diverse consumer preferences while optimizing physiological benefits.

[0057] The invention discloses a composition comprising:

[0058] (a) Fructooligosaccharide (FOS), 5–10% w / v, degree of polymerization 3–5,

[0059] (b) UT 18: arginine 26.13 mg, glycine 11.26 mg, citric acid 28.81 mg,

[0060] (c) An enhancer protein, ≥90% purity, in a nutraceutically acceptable carrier, adjusted to pH 6.8-7.4.

[0061] In a DSS-induced colitis mouse model, this formulation demonstrated significant improvements in body weight preservation, Disease Activity Index (DAI), colon length, and histopathology compared to single components. Integrated efficacy ranking across all measured parameters showed FOS+UT 18 as the top-performing combination, followed by EP, then FOS+UT 18+EP.

[0062] BRIEF DESCRIPTION OF DRAWINGS

[0063] Figure 1: Body weight changes over time in treated vs. control animals

[0064] Figure 2: Disease Activity Index (DAI) scores

[0065] Figure 3: Colon length and weight comparison

[0066] Figure 4: Relative organ weights

[0067] Figure 5: Serum biochemistry parameters

[0068] Figure 6: Hematology values across treatment groups

[0069] Figure 7: Disease Control

[0070] Figure 8: FOS

[0071] Figure 9: UT18

[0072] Figure 10: EP

[0073] Figure 11: FOS + UT18Figure 12: FOS + UT18 + EP

[0074] Figure 13: Disease Control and FOS

[0075] Figure 14: UT18

[0076] Figure 15: EP

[0077] Figure 16: FOS + UT18 and FOS + UT18 + EP

[0078] Figure 17: Comparative Analysis of Colon Length Preservation in Experimental Inflammatory Bowel Disease Models Following Nutraceutical Intervention

[0079] DETAILED DESCRIPTION OF THE INVENTION

[0080] The present invention provides a synergistic nutraceutical composition designed to promote and maintain gastrointestinal wellness through the combined action of three bioactive components — fructooligosaccharide (FOS), UT 18, and an enhancer protein — formulated in specific ratios and with specific preparation methods to achieve measurable and reproducible functional benefits. This composition has been developed through detailed experimentation to ensure that it is not a mere admixture but a synergistic blend where the combination of components produces effects significantly greater than the sum of their individual activities. The formulation is prepared in such a way that each component contributes uniquely, and their interaction amplifies the overall functional benefits in vitro.

[0081] The FOS used in the composition is preferably obtained via enzymatic hydrolysis of inulin extracted from chicory root or other suitable botanical sources. In the preferred embodiment, the FOS has an average degree of polymerization between 3 and 5, ensuring an optimal prebiotic effect without excessive osmotic activity that can occur with shorter chains. The FOS content in the composition is between 5% and 10% w / v. This concentration range was determined through experimental screening to produce significant stimulation of beneficial gut bacteria such as Bifidobacteria and Lactobacillus while avoiding gastrointestinal discomfort. In addition to its biological effect, FOS also serves as a soluble carrier matrix for UT 18 and EP, aiding in the uniform dispersion and stability of the final formulation.

[0082] UT 18 is a defined mixture of arginine, glycine, and citric acid in the precise quantities of 26.13 mg, 11.26 mg, and 28.81 mg, respectively, per unit formulation. Arginine is a semi-essential aminoacid with known roles in nitric oxide production, vascular regulation, and tissue repair. Glycine supports collagen synthesis and has documented anti-inflammatory and cytoprotective effects in gut epithelial cells. Citric acid serves as a, energy provider thru TCA cycle in mitochondria, natural preservative, pH regulator, and mild chelating agent, which helps maintain ionic balance and enhances amino acid stability. The inventors found that combining UT 18 with FOS and or EP enhanced epithelial wound healing and reduced oxidative stress more effectively than either component alone. UT 18 is included in a defined ratio relative to FOS and EP, typically between 2:1:1 and 4:2:1 by weight, which was optimized for both functional synergy and palatability in oral formulations.

[0083] The enhancer protein is isolated using aqueous extraction, followed by purification and lyophilization. It is then solubilized in phosphate-buffered saline at pH 7.2 prior to incorporation into the formulation. EP exhibits antioxidant, anti-inflammatory, and antimicrobial activities, with particular relevance to gut mucosal barrier function. EP alone can reduce oxidative stress in gut epithelial cells; however, when combined with UT 18 and FOS, the reduction in reactive oxygen species exceeds the additive effect by at least 10%, indicating a true synergistic interaction. The protein is sensitive to oxidation; therefore, handling and formulation under controlled conditions, preferably in an inert atmosphere, are recommended to preserve activity.

[0084] The nutraceutically acceptable carrier in the composition may be selected from water, isotonic saline, glycerol, maltodextrin, or combinations thereof. The choice of carrier influences solubility, taste, stability, and consumer acceptance. For liquid formats, isotonic saline or glycerol solutions are preferred to maintain osmolarity and viscosity. For dry powders and sachets, maltodextrin serves as a bulking and stabilizing agent. The formulation pH is adjusted between 6.8 and 7.4 to optimize the stability of EP and the solubility of amino acids, while maintaining conditions compatible with gut physiology and intended consumption.

[0085] The novelty of this invention lies in the synergistic enhancement of functional properties demonstrated through in vitro experimentation. The combination of FOS, UT 18, and EP in the specified ratio reduced TNF-α and IL-6 expression in human colonic epithelial cells stimulated with lipopolysaccharide by at least 20% more than the sum of effects from the individual components. In in vitro fecal fermentation assays, the composition produced at least 15% higher butyrate levels comparedto FOS alone, indicating improved fermentation efficiency or beneficial microbiota stimulation. In oxidative stress models using hydrogen peroxide, the EP– FOS combination lowered reactive oxygen species production by at least 10% compared to EP alone. In Caco-2 scratch assays, UT 18 combined with EP closed epithelial gaps 1.2 times faster than either component alone. These improvements were statistically significant and reproducible, confirming that the composition is more than a mere admixture.

[0086] The composition may be presented as a liquid suspension, dry powder, granules, sachets, capsules, or effervescent tablets. Each form offers different advantages depending on the intended consumer use. Liquid suspensions provide ready-to-use convenience, dry powders and sachets offer portability and stability, capsules allow precise dosage control and taste masking, and effervescent tablets provide rapid dissolution and improved palatability. All components are blended under an inert atmosphere, such as nitrogen, to minimize oxidation of EP and amino acids, thereby preserving the biological activity of the final product.

[0087] The preparation process ensures stability, homogeneity, and retention of bioactivity. EP is first dissolved in phosphate-buffered saline at pH 7.2. FOS is added under gentle stirring to maintain solubility and avoid protein precipitation. UT 18 is incorporated under continuous mixing to ensure uniform distribution of amino acids and citric acid throughout the formulation. The mixture is homogenized to achieve a consistent particle size and dispersion. The pH is adjusted to between 6.8 and 7.4 for optimal stability. Optionally, blending and homogenization may be performed under nitrogen to prevent oxidative degradation. The final mixture is filled into the chosen dosage form.

[0088] A preferred packaged product format includes two separate containers. The first contains EP in solubilized form to maintain protein structure and activity. The second contains a dry blend of FOS and UT 18, which is more stable in dehydrated form. The kit is accompanied by printed instructions describing reconstitution and oral consumption for supporting gastrointestinal wellness. This approach not only ensures stability but also enhances consumer convenience and shelf life.

[0089] Unlike existing products that combine prebiotics and proteins without measurable synergistic benefit, the claimed composition is optimized for specific ratios and preparation methods that yielddemonstrable in vitro synergy. It has been tested for multiple complementary effects, including antiinflammatory, antioxidant, microbiota-modulating, and epithelial repair, making it functionally superior to known formulations. The packaging method extends shelflife while preserving bioactivity.

[0090] Experimental studies confirm these advantages. In colonic epithelial cells treated with lipopolysaccharide, FOS alone reduced TNF-α by 15%, UT 18 by 10%, and EP by 18%, with a predicted additive effect of 43%. The claimed composition reduced TNF-α by 64%, representing a 21% greater effect than predicted. In butyrate production assays, FOS alone yielded 4.0 mmol / L, while the composition produced 4.6 mmol / L, a 15% improvement. In oxidative stress assays, EP alone reduced reactive oxygen species by 25%, whereas EP plus FOS reduced them by 37%, a 12% improvement over the expected additive value. In wound healing assays, UT 18 alone closed 60% of the wound area in 24 hours, EP alone closed 58%, with a predicted additive effect of 118%. The combination closed 140% relative to baseline, representing a 1.2× improvement.

[0091] Fructooligosaccharides (FOS) are prebiotic compounds that play a crucial role in modulating the gut microbiome. By promoting the growth of beneficial bacteria in the digestive system, FOS helps maintain a balanced microbial environment that is essential for gut health. This process leads to the production of short-chain fatty acids (SCFAs), which have been widely studied for their antiinflammatory properties. SCFAs not only support the integrity of the gut lining but also contribute to metabolic regulation by influencing energy balance, glucose metabolism, and lipid homeostasis. By fostering a healthy gut microbiome, FOS may help prevent digestive disorders, boost immune function, and enhance overall well-being.

[0092] Another key ingredient, UT 18, is an amino acid and short chain sugar complex designed to support cellular energy metabolism and stem cell chemoattraction. Stem cells play a fundamental role in tissue regeneration and repair, as they can differentiate into various specialized cell types. UT 188 may enhance the migration of stem cells to areas of the body that require repair, thereby supporting the body's natural regenerative processes. This ability to attract and activate stem cells is particularly significant for individuals recovering from injuries, those experiencing agerelated degeneration, or those looking to enhance overall cellular health.Brazzein, a non-caloric sweetener, offers metabolic benefits while being insulin-sensitive, making it a valuable ingredient for those managing blood sugar levels. Unlike conventional sugar, which can lead to spikes and crashes in blood glucose, brazzein provides sweetness without negatively impacting insulin sensitivity. This makes it a suitable option for individuals with diabetes, those following low-calorie diets, or anyone looking to maintain a stable metabolic rate. Additionally, brazzein may aid in weight management by reducing overall caloric intake without sacrificing taste, making it an ideal alternative for health-conscious consumers. Vitamin K, particularly in its KI and K2-MK7 forms, is a vital nutrient essential for bone mineralization and cardiovascular function. Vitamin K plays a key role in directing calcium to the bones while preventing it from accumulating in the arteries. This function is crucial for reducing the risk of osteoporosis and maintaining arterial flexibility, which contributes to heart health. Additionally, emerging research suggests that vitamin K may have a role in stem cell differentiation, potentially enhancing the body's ability to regenerate tissues and maintain cellular health over time. By incorporating vitamin K into a supplementation regimen, individuals may benefit from stronger bones, improved cardiovascular function, and better overall longevity.

[0093] The formulations designed using these ingredients are structured to build upon one another, each step providing additional benefits to support overall health. Formula 1 consists of FOS, UT 188, and brazzein, forming a strong foundation focused on gut microbiome modulation, metabolic support, and stem cell chemoattraction. The inclusion of FOS ensures that the gut microbiome remains balanced, which in turn supports digestion, immune function, and nutrient absorption. UT 188 enhances cellular energy metabolism and stem cell activity, supporting tissue repair and regeneration. Brazzein, as a natural sweetener with metabolic benefits, ensures that the formulation is suitable for individuals mindful of their blood sugar levels.

[0094] Building upon the foundation of Formula 1, Formula 2 introduces vitamin K to the mix. This addition enhances the formulation’s ability to support bone health, cardiovascular function, and hormonal balance while continuing to promote stem cell differentiation. With the inclusion of vitamin K, individuals may benefit from improved calcium utilization, reduced arterial calcification, and enhanced overall skeletal integrity. This formula is ideal for individuals seeking a more comprehensiveapproach to health, particularly those looking to prevent osteoporosis, support heart health, or maintain optimal hormonal function.

[0095] Formula 3 completes the sequence by incorporating an enhancer protein, which adds regenerative and longevity support to the previous formulations. With the addition of the enhancer protein’s bioactive compounds, this formula enhances telomere maintenance, promoting healthier aging at the cellular level. This final formulation is particularly suited for individuals looking to maximize their health span, improve regenerative potential, and support long-term wellness. The combination of FOS, UT 188, brazzein, vitamin K, and enhancer protein offers a holistic approach to health, addressing gut health, metabolic function, cardiovascular support, bone strength, and longevity in a single, well-rounded supplement.

[0096] Ayurvedic bioactives can be incorporated into the disclosed formulations. Ayurvedic medicine has long been recognized for its use of natural compounds to enhance well-being, and several key bioactives complement the existing ingredients in the formulations. Ashwagandha, a wellknown adaptogen, is prized for its ability to reduce stress and enhance overall vitality. Stress plays a significant role in metabolic disorders, immune dysfunction, and premature aging. By incorporating ashwagandha, the formulation may help improve resilience to stress, enhance energy levels, and support overall mental and physical well-being.

[0097] Shilajit, another Ayurvedic bioactive, is commonly used to boost energy levels and support cognitive function. This mineral-rich compound has been shown to enhance mitochondrial function, which is essential for cellular energy production. Additionally, shilajit may improve nutrient absorption, ensuring that the body effectively utilizes the vitamins and minerals provided by the formulations. Its cognitive-enhancing properties also make it beneficial for individuals looking to improve focus, memory, and mental clarity.

[0098] Curcumin, the active compound in turmeric, is widely recognized for its powerful antiinflammatory and antioxidant properties. Chronic inflammation has been linked to a variety of health conditions, including cardiovascular disease, neurodegenerative disorders, and metabolic dysfunction. By incorporating curcumin into the formulations, individuals may benefit from reduced inflammation,enhanced immune function, and improved cellular protection against oxidative stress. Curcumin is an excellent biomolecule that helps to maintain overall health and prevents chronic diseases.

[0099] To cater to diverse consumer preferences, these formulations can be offered in multiple delivery forms, ensuring accessibility and ease of use. An oral drink is an excellent option for those who prefer a convenient and quickly absorbable format. Liquid supplements are often favored by individuals who have difficulty swallowing pills or who want faster nutrient absorption. This format ensures that the active ingredients reach the digestive system efficiently, providing immediate benefits.

[0100] Gummy tablets offer a flavorful and enjoyable alternative, especially for those who prefer a chewable option. Gummies are particularly appealing to individuals who dislike swallowing capsules or tablets, making them an excellent choice for a wide range of consumers, including children and older adults. They also provide a more enjoyable way to incorporate supplementation into daily routines, increasing adherence to health regimens.

[0101] In traditional supplementation methods, solid dosage forms such as capsules or tablets remain a reliable option. Capsules and tablets offer precise dosing, convenience, and portability, making them a preferred choice for individuals who want a structured and consistent supplementation routine. These forms also provide a stable shelf life, ensuring that the active ingredients remain effective over time.

[0102] Overall, these formulations represent a comprehensive approach to health, integrating cuttingedge nutritional science with time-tested Ayurvedic principles. By combining key ingredients such as FOS, UT 188, brazzein, vitamin K, and enhancer protein, along with optional Ayurvedic bioactives like ashwagandha, shilajit, and curcumin, these formulations offer holistic benefits that support gut health, metabolic function, regeneration, longevity, and overall well-being. The availability of multiple delivery forms further ensures that individuals can choose the most convenient and effective way to incorporate these supplements into their daily lives.

[0103] PHARMACOLOGICAL EVALUATION OF TEST FORMULATIONSA study was performed to assess the pharmacological evaluation of test formulations in male Balb / c mice. The study provided information on the efficacy of test formulations by oral route for the assessment of anti-colitis effect in Dextran Sulfate Sodium (DSS) induced colitis in male Balb / c mice.

[0104] LIST OF ABBREVIATIONS

[0105] Abbreviation Full Form

[0106] AGC Arginine, Glycine, and Citric acid

[0107] AST Aspartate Aminotransferase

[0108] ALT Alanine Aminotransferase

[0109] ALP Alkaline Phosphatase

[0110] BUN Blood Urea Nitrogen

[0111] BW Body Weight

[0112] COA Certificate Of Analysis

[0113] CPCSEA Committee for the Purpose of Control and Supervision on Experimental Animals

[0114] CHOL Cholesterolcm Centimeters

[0115] CREA CreatininedL Deciliter

[0116] DSS Dextran Sulfate Sodium

[0117] fL Femtolitre

[0118] FOS Fructooligosaccharide

[0119] GLP Good Laboratory Practices

[0120] GLU Glucoseg Gram

[0121] HCT Hematocrit

[0122] HDL High-Density Lipids

[0123] HGB Hemoglobin

[0124] IAEC Institutional Animal Ethics Committee LDL Low-Density Lipids

[0125] MCV Mean Corpuscular Volume

[0126] MCH Mean Corpuscular Hemoglobin MCHC Mean Corpuscular Hemoglobin Concentration EP Enhancer protein

[0127] mg Milligram

[0128] NA Not Applicable

[0129] PBS Phosphate-buffered Saline

[0130] PCT Plateletcrit

[0131] PDW Platelet Distribution Width

[0132] pg Picogram

[0133] PLT Platelet Count

[0134] RBC Red Blood Cell Count

[0135] RDW-CV Red Cell Distribution Width – Coefficient of VariationRDW-SD Red Cell Distribution Width - Standard Deviation

[0136] TGL Triglycerides

[0137] UT 18 Utopia Therapeutics 18

[0138] WBC White Blood Cell Count

[0139] μg Microgram

[0140] μL Microliters

[0141] % Percentage

[0142] MATERIALS AND METHODS

[0143] The experimental study was conducted using Balb / c mice, which are internationally recognized as an ideal test species for preclinical research due to their well-documented immunological characteristics and the abundance of historical data available on them. These mice were procured from GV Safety Assessment Platform Pvt. Ltd., which is registered under the CPCSEA with registration number 2173 / PO / RcBiBt / S / 20 / CPCSEA. The selected animals were healthy, of good quality, and within the age range of 6 to 8 weeks. The average body weight of the male mice at the time of randomization was approximately 21 ± 2 grams.

[0144] A total of 51 animals were used for the study. Each animal was individually identified and housed in stainless steel cages, one mouse per cage, to ensure accurate data collection and prevent inter-animal variability. The animals were provided with pelleted rodent feed, which was available ad libitum throughout the study. Environmental conditions were strictly maintained to ensure animal welfare and consistency in results. The room temperature was maintained at 22°C ± 3°C, and the relative humidity ranged from 30% to 70%. A 12-hour light / dark cycle was implemented to mimic natural circadian rhythms.

[0145] Water was provided ad libitum using an Aqua Guard purification system to ensure its quality and safety. Cage cleaning was performed twice weekly to maintain hygiene and minimize the risk of infection. Before the commencement of the experiment, all animals underwent a thorough veterinaryexamination followed by a minimum acclimatization period of seven days in the experimental room to ensure that they adapted well to the environment and experimental conditions. This preparatory step was essential for the randomization process and to ensure the overall reliability and reproducibility of the study results.

[0146] s. Materials / Biological Material Source of Materials / Biological No. Material

[0147] 1 Enhancer protein — Procured Online from market

[0148] 2 Fructooligosaccharide (FOS) — Procured Online from market

[0149] 3 UT 18 (Citric acid with amino acids: arginine & — Procured Online from market glycine)

[0150] 4 Ashwagandha — Procured Online from market

[0151] 5 Shilajit — Procured Online from market

[0152] 6 Curcumin — Procured Online from market

[0153]

[0154] Study Design:

[0155] The study was aimed at evaluating the pharmacological activity of test formulations in male Balb / c mice by the oral route of administration. After acclimatization of 7 days, animals were randomized into 7 groups based on body weights. Animals belonging to each group received their respective ready-to-use formulations as mentioned in the following table:

[0156] Example, Table 1: Animal Study Groups, Formulation, Dosage, and Route of Administration Group Animal Description Dose Volume Route of Dosing No. Administration

[0157] (ml / kg) Frequency

[0158] G-1 01 – 08 Disease control 10 ml / kg Per Oral (PO) Once daily

[0159] G-2 09 - 16 FOS 10 ml / kg Per Oral (PO) Once daily

[0160] G-3 17 -24 UT 18 10 ml / kg Per Oral (PO) Once daily

[0161]

[0162] G-4 25 -32 EP 10 ml / kg Per Oral (PO) Once daily

[0163] G-5 33 -40 FOS +UT 18 10 ml / kg Per Oral (PO) Once daily

[0164] G-6 41 -48 FOS +UT 18 + 10 ml / kg Per Oral (PO) Once daily

[0165] EP

[0166] G-7 49 - 51 Sham - - -

[0167]

[0168] Formulation preparation;

[0169] A 10% (w / v) solution of Fructooligosaccharide (FOS) was prepared in sterile 1X Phosphate Buffered Saline (PBS). For the UT 18 group, an amino acid–organic acid composite consisting of arginine (26.13 mg), glycine (11.26 mg), and citric acid (28.81 mg) was dissolved in 6.0 mL of 1X PBS to yield a homogeneous AGC mixture. For the EP group, 2.2 mL of enhancer protein was solubilized in 1.8 mL of 1X PBS. All formulations were freshly prepared under aseptic conditions before administration.

[0170] Test Item Name AGC Sweetspot EP

[0171] IUPAC Name NA NA NA

[0172] CAS No. NA NA NA

[0173] Batch No. 9 B / FOS25043 xxxx

[0174] Date of Mfg. NA NA xxxx

[0175]

[0176] Date of Exp. NA NA xxxx Source of Test Item Details WTFABA WTFABA WTFABA

[0177] Biocatalyst WT FABA WT FABA WT FABA

[0178] Therapeutic Activity Aminosalicylates Prebiotic Gut health

[0179] Characteristics White powder Viscous solution Solution

[0180] Solubility 1X PBS 1X PBS 1X PBS

[0181] Dosage Form Injection Injection Injection

[0182] Storage Conditions Room temperature Room temperature 2-8 °C

[0183]

[0184] Dose levels Single-dose level

[0185] Study Duration 21 days, including 7 days acclimatization. Administration of test item Daily, once for each test formulation.

[0186] Dosage Details:

[0187] Dosage Regimen Pre-clinical

[0188] I. Drug Dose NA

[0189] II. Duration of treatment 14 consecutive days

[0190] III. Route of administration Oral.

[0191] *The dose for the mouse was extrapolated using standard guidelines.

[0192] PROCEDURESI. Dose Formulations:

[0193] A 10% (w / v) solution of Fructooligosaccharide (FOS) was prepared in sterile 1X Phosphate Buffered Saline (PBS). For the UT18 group, an amino acid–composite consisting of arginine (26.13 mg), glycine (11.26 mg), and citric acid(28.81mg) was dissolved in 6.0 mL of 1X PBS to yield a homogeneous AGC mixture. For the EP group, 2.2 mL of enhancer protein was solubilized in1.8mLof1X PBS. All formulations were freshly prepared under aseptic conditions before administration.

[0194] II. Experimental Procedures:

[0195] After the acclimatization period, the body weights of mice were recorded. A total of 51 mice were randomly divided into seven groups (n = 8 per group), while the sham group had only 3 mice: PBS alone, FOS alone, UT18 alone, EP alone, FOS + UT18 combination, FOS + UT18 + EP combination, and sham groups. Initially, the FOS alone group received the formulation at 100% concentration. Mortality was observed within the first two days. The concentration was then reduced to 50%, but mortality persisted. As a result, a three-day dosing holiday was implemented. The study was restarted thereafter and considered as Day 1. From Day 1 to Day 4, animals received 5%FOS, which was then increased to 10% from Day 5 onwards and continued until Day 14. FromDay1toDay 7, all groups received their respective formulations via oral dosing twice daily. From Day 8 to Day 14, colitis was induced by administering dextran sulfate sodium(DSS) in the drinking water, and the test formulations were continued once daily via oral gavage. Throughout the study, body weight, clinical observations, and DSS-containing drinking water intake were recorded daily for all animals. Fecal samples were collected on Day 7 (before DSS administration) and again on Day 15 for hemoccult testing to evaluate gastrointestinal bleeding. On Day 15, all animals were euthanized, and a full necropsy was performed. Major organs — including the liver, heart, spleen, lungs, kidneys, brain, and colon — were collected, weighed, and preserved in 10% formalin. A portion of the liver was stored at -80°C for further analysis, and colon length was measured and recorded. The liver and colon were processed for histopathological evaluation. Blood was collected for hematological analysis, and serum was separated for biochemical assessments.III. Clinical Observations:

[0196] General clinical observations were conducted twice daily for morbidity and mortality, and detailed clinical observations were conducted once daily. The following observations were made: 1. Mortality:

[0197] On day 13, A.no - 3, 6, 7 were found dead.

[0198] On day 15, A.no - 11, 13, 16 were found dead.

[0199] On day 16, A.no - 26, 34, 39, 43, 47 were found dead.

[0200] 2. Abnormal observation and morbidity:

[0201] Rectal bleeding was observed in A.no 2, 27, 28, 29, 30, 38, 39 on day -13.

[0202] Diarrhea was observed in A.no 8, 11, 12, 25, 33, 48 on day – 13.

[0203] Diarrhea with rectal bleeding was observed in A.no 24 on day - 13.

[0204] Rectal bleeding was observed in A.no 10, 12, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 33, 34, 35, 38, 39, 41, 43, 44, 45, 46 on day – 14.

[0205] Diarrhea was observed in A.no 36 on day - 36.

[0206] 3. Postmortem findings:

[0207] A yellow mass around the thymus was observed in A. no. 42.

[0208] IV. Conclusion:

[0209] In the DSS-induced colitis study, comparative assessment across multiple efficacy parameters revealed distinct treatment responses. Based on body weight trends, the order of recovery was: DC > FOS+UT18 > FOS > EP > UT18 > FOS+UT18+EP. Disease Activity Index, which included body weight loss, diarrhea scoring, and occult blood positivity, followed the severity pattern: DC > FOS > UT18 > FOS+UT18+EP> EP> FOS+UT18. Colon length analysis indicated protective effects in the order: FOS+UT18+EP > FOS > EP > FOS+UT18 > UT18 > DC, while the relative colonweight-to-body weight ratio ranked: DC > UT18 > FOS+UT18+EP > FOS > EP> FOS+UT18. Hematology did not reveal any significant alterations across treatment groups. Serum biochemistry showed that FOSsignificantly elevated ALP, total cholesterol, glucose, and LDL levels, whereas the combination of FOS with EP and UT18 notably increased triglycerides. EP alone led to elevated ALP levels. No hepatic abnormalities were observed in histopathological evaluations. Colon histopathology for inflammation and ulceration severity ranked as: DC > FOS > UT18 > FOS+UT18 > FOS+UT18+EP> EP. Visual scoring of rectal bleeding also followed: DC > UT18 > FOS > FOS+UT18> FOS+UT18+EP > EP. Upon integrated efficacy ranking across all parameters at the given dose, strength, and treatment duration, the overall order of therapeutic benefit was:

[0210] FOS+UT18 > EP > FOS+UT18+EP > FOS > UT18 > DC.

[0211] Parameter Ranking (Best to Worst)

[0212] Body Weight FOS+UT18 > EP > FOS > UT18 > FOS+UT18+EP >

[0213] DC

[0214] Disease Activity Index (DAI) FOS+UT18 > EP > FOS+UT18+EP > UT18 > FOS >

[0215] DC

[0216] Colon Length FOS+UT18+EP > FOS > EP > FOS+UT18 > UT18 >

[0217] DC

[0218] Colon Weight / Body Weight Ratio FOS+UT18 > EP > FOS > FOS+UT18+EP > UT18 >

[0219] DC

[0220] Serum Biochemistry FOS+UT18+EP ~ EP > FOS > UT18 > DC

[0221] (LDL / Choi / ALP etc.)

[0222] Colon Histopathology EP > FOS+UT18+EP > FOS+UT18 > UT18 > FOS >

[0223] DC

[0224] Rectal Bleeding (Image-based) EP > FOS+UT18+EP > FOS+UT18 > FOS > UT18 >

[0225] DC

[0226]

[0227] Overall Ranking (Cumulative FOS+UT18 > EP > FOS+UT18+EP > FOS > UT18 Efficacy) > DC

[0228]

[0229] The study concluded that FOS+UT 18, as well as EP, shows high efficacy in preventing and ameliorating the mild to moderate ulcerative colitis in the DSS-induced micemodel. Further studies are recommended to optimize the therapeutic dose of the test formulations as well as establish a safety profile.

[0230] STUDY GROUPS: Pharmacology evaluation of test formulations, In-Vivo through oral route of delivery.

[0231] Example, Table 2. Pharmacology Groups in animals.

[0232] s. Animals Test Formulation Dose Route of Time Point

[0233] No. Volume Administration (Excluding Acclimatization)

[0234] 1 3 M PBS 10 ml / Kg Per Oral (PO) 16 days

[0235] 2 8 M FOS 10 ml / Kg Per Oral (PO) 16 days

[0236] 3 37 M UTI 10 ml / Kg Per Oral (PO) 16 days

[0237] 4 5 M EP 10 ml / Kg Per Oral (PO) 16 days

[0238] 5 37 M FOS + UTI-8 10 ml / Kg Per Oral (PO) 16 days

[0239] 6 8 M FOS + UTI-8 + 10 ml / Kg Per Oral (PO) 16 days

[0240] EP

[0241]

[0242] 7 8 M SHAM 10 ml / Kg — 16 days

[0243]

[0244] All the Groups except the SHAM group were administered formulations.

[0245] Example, Table3: Summary of body weights(g) of animals

[0246] 5% 5% 5% 10% 10% 10% 10% 10% FOS FOS FOS FOS FOS FOS FOS FOS

[0247]

[0248] Group A. Day Day Day Day Day Day Day Day No 1 2 3 4 5 6 7 8

[0249] Disease Control 1 22 23 23 23 23 23 23 22

[0250] 2 24 24 24 24 25 25 25 25

[0251] 3 22 22 22 22 22 22 22 23

[0252] 4 22 22 22 22 22 23 23 23

[0253] 5 22 22 22 22 22 22 22 22

[0254] 6 20 21 22 22 22 22 23 23

[0255] 7 23 22 22 22 23 23 23 23

[0256] 8 21 22 22 22 22 23 23 24

[0257] FOS 9 22 23 23 24 25 25 26 26

[0258]

[0259] 10 25 26 27 27 27 28 28 28

[0260] 11 22 23 23 22 22 22 22 21

[0261] 12 25 25 24 25 24 25 25 25

[0262] 13 — — — — — — — —

[0263] 14 20 21 21 20 21 21 21 21

[0264] 15 24 24 24 24 24 24 25 23

[0265] 16 23 23 23 23 23 22 22 23

[0266]

[0267] UT18 17 22 22 22 22 22 22 22 22

[0268] 18 25 25 24 25 24 24 24 24

[0269] 19 23 23 23 23 23 23 23 24

[0270] 20 25 25 25 24 25 25 25 25

[0271] 21 22 22 22 23 22 23 22 22

[0272] 22 22 23 23 22 23 24 23 24

[0273] 23 22 22 22 22 22 22 22 21

[0274]

[0275] 24 22 22 22 22 22 23 22 23

[0276] EP 25 25 25 25 26 26 26 26 28

[0277] 26 21 21 21 21 21 22 21 19

[0278] 27 25 25 24 24 25 25 25 25

[0279] 28 23 24 24 25 25 26 26 27

[0280] 29 24 24 24 24 25 25 24 24

[0281] 30 22 21 21 21 22 22 23 24

[0282] 31 25 24 24 24 22 21 19 18

[0283] 32 23 23 23 22 23 23 22 22

[0284] FOS + UT18 33 25 20 20 18 18 17 18 17

[0285]

[0286] 34 23 23 23 23 23 22 22 23

[0287] 35 24 24 24 25 25 25 26 27

[0288] 36 23 23 23 22 23 23 23 22

[0289] 37 22 22 22 22 22 21 22 21

[0290]

[0291] 38 21 24 24 24 24 24 25 24

[0292] 39 23 23 23 22 23 23 22 21

[0293] 40 21 22 22 22 22 21 22 22

[0294] FOS + UT18 + EP 41 21 22 22 21 21 21 22 21

[0295] 42 24 22 22 22 23 22 23 23

[0296] 43 21 21 21 21 20 20 21 21

[0297] 44 25 26 25 25 25 25 25 25

[0298] 45 23 24 24 25 25 26 26 27

[0299] 46 23 24 24 25 26 26 26 27

[0300] 47 23 23 23 22 22 23 22 22

[0301] 48 21 22 22 21 22 22 21 21

[0302] Sham 49 20 20 21 21 21 22 22 23

[0303] 50 20 21 22 22 22 23 23 23

[0304] 51 21 21 22 22 23 23 23 24

[0305]

[0306] 5% 5% 5% 10% 10% 10% 10% 10%

[0307] FOS FOS FOS FOS FOS FOS FOS FOS

[0308] Group A.No Day9 Day10 Day11 Day12 Day13 Day14 Day15 Day16

[0309] Disease 1 22 23 24 23 22 20 19 16 control

[0310] 2 24 24 23 24 23 22 21 19

[0311] 3 23 22 20 18 15 - - -

[0312] 4 24 23 23 23 22 21 19 16

[0313] 5 22 22 23 22 22 20 18 16

[0314] 6 23 22 21 19 16 - - -

[0315] 7 22 21 20 18 15 - - -

[0316] 8 23 22 23 23 22 21 19 17

[0317] FOS 9 27 27 27 26 26 26 23 21

[0318] 10 29 30 30 29 28 27 26 23

[0319] 11 19 18 18 16 16 16 - -

[0320]

[0321] 12 25 25 26 25 25 23 20 17

[0322] 13 - - - - - - - -

[0323] 14 22 20 21 20 18 17 16 16

[0324] 15 25 23 23 22 22 21 20 18

[0325] 16 21 19 19 17 16 15 - -

[0326] UT18 17 22 21 21 22 21 21 20 18

[0327] 18 24 24 24 23 22 23 22 20

[0328] 19 23 23 23 23 23 22 22 21

[0329] 20 25 24 25 24 23 22 20 18

[0330] 21 22 23 22 22 21 20 18 17

[0331] 22 23 23 23 22 22 21 21 19

[0332] 23 22 22 22 22 21 21 20 18

[0333] 24 23 22 23 22 22 21 20 17

[0334] EP 25 28 25 27 28 27 26 22 20

[0335]

[0336] 26 18 17 16 15 15 15 - -

[0337] 27 24 22 22 21 20 18 17 16

[0338] 28 28 26 28 28 27 24 21 20

[0339]

[0340] 29 25 24 23 23 23 20 18 18

[0341] 30 24 23 23 23 22 22 22 20

[0342] 31 18 19 20 22 22 22 21 19

[0343] 32 21 19 19 17 17 18 17 16

[0344] FOS+UT 33 17 16 16 16 15 16 18 18 18

[0345] 34 23 23 23 23 21 19 17 -

[0346] 35 28 28 29 28 27 26 24 21

[0347] 36 23 22 22 22 22 21 21 20

[0348] 37 21 21 21 20 20 20 20 19

[0349] 38 25 25 25 25 25 25 22 20

[0350] 39 21 18 18 17 17 18 16 -

[0351]

[0352] 40 22 21 21 21 20 18 17 17

[0353] FOS+UT 41 21 21 20 18 19 19 18 18 18 + EP

[0354] 42 22 22 22 22 22 22 21 19

[0355] 43 21 20 19 20 19 18 15 -

[0356] 44 25 24 24 23 23 21 20 18

[0357] 45 27 27 27 28 27 26 23 21

[0358] 46 26 27 28 26 27 25 22 20

[0359] 47 22 21 21 18 18 17 17 -

[0360] 48 21 21 21 20 19 20 19 19

[0361] SHAM 49 23 24 24 25 25 25 26 26

[0362] 50 24 24 25 25 26 26 27 27

[0363] 51 24 24 25 25 26 26 27 27

[0364]

[0365] Note: "-" denotes not available.

[0366] Example, Table 4: Summary of Hematology ParametersGroup Name N WBC Neutro Lymphoc Mixed RBC HGB 0 (10^9 / L) Phils ytes cell (10A12 / L) (g / dL)

[0367] (10^9 / L) (10^9 / L) (10^9 / L)

[0368] DSS CONTROL 1 5.36 2.52 2.11 0.73 8.01 15.3

[0369] 2 5.97 2.41 2.96 0.60 8.66 16.3

[0370] 3 - - - - - -

[0371] 4 3.09 1.47 1.18 0.44 7.92 15.3

[0372] 5 - 3.78 3.39 1.31 7.67 14.7

[0373] 6 - - - - - -

[0374]

[0375] 7 - - - - - -

[0376] 8 12.81 4.25 6.68 1.88 7.74 14.1

[0377] FOS 9 35.74 6.57 26.16 3.01 8.19 16.7

[0378] 10 26.30 6.74 17.43 2.13 7.85 15.9

[0379] 11 - - - - - -

[0380] 12 11.34 3.57 6.37 1.40 10.35 19.7

[0381] 13 - - - - - -

[0382]

[0383] 14 8.33 3.81 3.77 0.75 8.19 16.0

[0384] 15 5.10 1.24 3.52 0.34 9.05 16.9

[0385] 16 - - - - - -

[0386] UT18 17 10.71 2.28 7.54 0.89 9.78 18.3

[0387] 18 10.12 1.50 7.45 1.17 9.70 18.9

[0388] 19 7.08 1.64 4.80 0.64 6.18 12.4

[0389] 20 8.39 0.55 7.22 0.62 8.37 16.2

[0390] 21 6.22 0.32 5.48 0.42 8.32 16.1

[0391] 22 20.15 4.46 13.91 1.78 9.11 17.5

[0392] 23 3.03 0.81 1.91 0.31 7.77 14.9

[0393]

[0394] 24 1.42 0.35 0.95 0.12 7.41 14.2

[0395] EP 25 21.08 2.43 17.08 1.57 8.48 18.1

[0396] 26 - - - - - -

[0397] 27 8.98 0.33 8.25 0.40 7.91 16.4

[0398]

[0399] 28 8.60 0.37 7.80 0.43 7.81 16.5

[0400] 29 14.73 2.20 11.42 1.11 8.16 16.2

[0401] 30 31.24 6.76 21.53 2.95 7.33 15.5

[0402] 31 11.69 1.15 9.88 0.66 8.01 13.7

[0403] 32 12.58 1.82 9.79 0.97 8.68 16.5

[0404] FOS+UT18 33 10.45 2.22 7.35 0.88 9.09 17.4

[0405] 34 - - - - - -

[0406] 35 22.74 6.66 13.44 2.64 8.09 16.0

[0407] 36 12.48 5.02 5.66 1.80 7.91 16.2

[0408] 37 7.90 2.53 4.69 0.68 8.54 16.8

[0409] 38 - - - - - -

[0410] 39 - - - - - -

[0411] 40 3.86 0.57 2.93 0.36 7.82 14.7

[0412] FOS+UT18+EP 41 10.92 1.90 7.93 1.09 9.27 18.7

[0413] 42 20.90 4.28 13.84 2.78 7.70 16.0

[0414]

[0415] 43 - - - - - -

[0416] 44 8.50 0.97 6.84 0.69 9.08 18.2

[0417] 45 19.10 0.60 17.85 0.65 2.10 4.3

[0418] 46 10.15 0.44 9.12 0.59 4.82 10.3

[0419] 47 - - - - - -

[0420] 48 7.39 1.80 4.78 0.81 8.10 14.9

[0421] Sham 49 3.93 0.38 3.24 0.31 7.79 13.6

[0422] 50 4.39 0.21 3.91 0.27 6.93 11.5

[0423] 51 4.05 0.60 3.09 0.36 8.63 14.1

[0424]

[0425] Note: "-" denotes not available.

[0426] A.No Hct MCV (fL) MCH (pg) MCHC RDW-CV (g / l) (fL)

[0427] DSS 1 0.257 32.1 19.1 595 0.265 CONTRO

[0428] L 2 0.288 33.2 18.8 566 0.257

[0429] 3 - - - - -

[0430]

[0431] 4 0.253 32 19.3 605 0.265

[0432] 5 0.248 32.3 19.2 593 0.238

[0433] 6 - - - - -

[0434] 7 - - - - -

[0435] 8 0.234 30.2 18.2 603 0.285

[0436] FOS 9 0.267 32.6 20.4 625 0.257

[0437] 10 0.247 31.5 20.3 644 0.265

[0438] 11 - - - - -

[0439] 12 0.355 34.3 19 555 0.25

[0440] 13 - - - - -

[0441] 14 0.265 32.4 19.5 604 0.257

[0442] 15 0.3 33.2 18.7 563 0.257

[0443] 16 - - - - -

[0444] UT18 17 0.331 33.8 18.7 553 0.277

[0445] 18 0.329 33.9 19.5 574 0.277

[0446]

[0447] 19 0.19 30.7 20.1 653 0.244

[0448] 20 0.274 32.7 19.4 591 0.257

[0449]

[0450] 21 0.271 32.6 19.4 594 0.257

[0451] 22 0.303 33.3 19.2 578 0.257

[0452] 23 0.25 32.2 19.2 596 0.238

[0453] 24 0.236 1.8 19.2 602 0.265

[0454] EP 25 0.269 31.7 21.3 673 0.305

[0455] 26 - - - - -

[0456] 27 0.252 31.8 20.7 651 0.265

[0457] 28 0.248 31.8 21.1 665 0.265

[0458] 29 0.27 33.1 19.9 600 0.257

[0459] 30 0.218 29.8 21.1 711 0.324

[0460] 31 0.259 32.3 17.1 529 0.238

[0461] 32 0.285 32.8 19 579 0.257

[0462]

[0463] FOS+UT 33 0.302 33.2 19.1 576 0.277 18

[0464] 34 - - - - -

[0465] 35 0.232 28.7 19.8 690 0.346

[0466] 36 0.258 32.6 20.5 628 0.257

[0467] 37 0.283 33.1 19.7 594 0.257

[0468] 38 - - - - -

[0469] 39 - - - - -

[0470] 40 0.25 32 18.8 588 0.238

[0471] FOS+UT 41 0.312 33.7 20.2 599 0.277 18 + EP

[0472] 42 0.249 32.4 20.8 643 0.257

[0473] 43 - - - - -

[0474] 44 0.301 33.1 20 605 0.257

[0475] 45 0.059 28.3 20.5 729 0.204

[0476] 46 0.14 29.1 21.4 736 0.252

[0477] 47 - - - - -

[0478]

[0479] 48 0.265 32.7 18.4 562 0.238

[0480] SHAM 49 0.257 33 17.5 529 0.231

[0481] 50 0.219 31.6 16.6 525 0.193

[0482] 51 0.289 33.5 16.3 488 0.206

[0483]

[0484] Gro A. N Het MC MC MCH RDW- RDW- PLT MPV PD PCT 0 W up V H C (g / 1) CV SD (10^9 / L (fL) (%) Na (fL) (Pg) (fL) (fL) )

[0485] me

[0486] DS 1 0.25 32.1 19.1 595 0.265 45.1 354 7.7 16.8 0.27 S 7 4 CO NT 2 0.28 33.2 18.8 566 0.257 44.1 353 7.6 17.3 0.26 RO 8 9 L

[0487] 3 - - - - - - - - - -

[0488] 4 0.25 32 19.3 605 0.265 47 323 7.8 16.3 0.25 3 3

[0489] 5 0.24 32.3 19.2 593 0.238 43.2 307 7.7 16.8 0.23 8 7

[0490]

[0491] 6 - - - - - - - - - -

[0492] 7 - - - - - - - - - -

[0493] 8 0.23 30.2 18.2 603 0.285 51.8 317 7.1 12 0.22 4 7

[0494] FO 9 0.26 32.6 20.4 625 0.257 45.1 354 7.7 16.8 0.27 S 7 4

[0495] 10 0.24 31.5 20.3 644 0.265 44.1 353 7.6 17.3 0.26 7 9

[0496] 11 - - - - - - - - - -

[0497]

[0498] 12 0.35 34.3 19 555 0.25 47 323 7.8 16.3 0.25 5 3

[0499] 13 - - - - - 43.2 307 7.7 16.8 0.23

[0500] 7

[0501] 14 0.26 32.4 19.5 604 0.257 - - - - - 5

[0502] 15 0.3 33.2 18.7 563 0.257 - - - - -

[0503] 16 - - - - - 51.8 317 7.1 12 0.22

[0504] 7

[0505]

[0506] UT 17 0.33 33.8 18.7 553 0.277 47 264 7.4 14.9 0.19 18 1 4

[0507] 18 0.32 33.9 19.5 574 0.277 48 272 11.4 22.3 0.31 9 1

[0508] 19 0.19 30.7 20.1 653 0.244 - - - - -

[0509] 20 0.27 32.7 19.4 591 0.257 48 101 7.1 9.6 0.07 4 2

[0510] 21 0.27 32.6 19.4 594 0.257 - - - - - 1

[0511] 22 0.30 33.3 19.2 578 0.257 47 369 7.7 16.8 0.28 3 3

[0512] 23 0.25 32.2 19.2 596 0.238 46 342 8 18.2 0.27

[0513] 5

[0514]

[0515] 24 0.23 1.8 19.2 602 0.265 - - - - - 6

[0516] EP 25 0.26 31.7 21.3 673 0.305 49.9 306 8 17 0.24

[0517] 9 4

[0518] 26 - - - - - 49.9 293 7.6 15.6 0.22

[0519] 3

[0520] 27 0.25 31.8 20.7 651 0.265 41.2 402 7.3 14.9 0.29 2 6

[0521]

[0522] 28 0.24 31.8 21.1 665 0.265 47 263 8.7 19.9 0.22 8 9

[0523] 29 0.27 33.1 19.9 600 0.257 48 288 8.1 17.8 0.23

[0524] 5

[0525] 30 0.21 29.8 21.1 711 0.324 49.9 323 7.5 15.8 0.24 8 3

[0526] 31 0.25 32.3 17.1 529 0.238 45.1 351 7.5 16.6 0.26 9 5

[0527] 32 0.28 32.8 19 579 0.257 44.1 291 7.6 15.1 0.22 5 2

[0528] FO 33 0.30 33.2 19.1 576 0.277 51.8 308 7.3 14.2 0.22 S+ 2 4 UT

[0529] 18 34 - - - - - - - - - -

[0530] 35 0.23 28.7 19.8 690 0.346 48 270 11 22.6 0.29 2 7

[0531]

[0532] 36 0.25 32.6 20.5 628 0.257 48 269 10.7 22.6 0.28 8 9

[0533] 37 0.28 33.1 19.7 594 0.257 47 261 11.4 23.5 0.29 3 7

[0534] 38 - - - - - 53.7 265 9.1 17 0.24

[0535] 2

[0536]

[0537] 39 - - - - - 38.4 343 7.5 15.6 0.25

[0538] 7

[0539] 40 0.25 32 18.8 588 0.238 47 268 12.1 23 0.32

[0540] 6

[0541] FO 41 0.31 33.7 20.2 599 0.277 49.9 264 8.7 19.4 0.22 S+ 2 9 UT

[0542] 18 42 0.24 32.4 20.8 643 0.257 48.9 341 7.2 14.6 0.24 + 9 7 EP

[0543] 43 - - - - - - - - - -

[0544] 44 0.30 33.1 20 605 0.257 49.9 267 7.9 16.6 0.21 1

[0545] 45 0.05 28.3 20.5 729 0.204 35.5 272 7.8 16.3 0.21 9 2

[0546] 46 0.14 29.1 21.4 736 0.252 42.2 471 7 13.2 0.33

[0547] 1

[0548] 47 - - - - - - - - - -

[0549] 48 0.26 32.7 18.4 562 0.238 42.2 356 7.6 15.8 0.27 5

[0550] SH 49 0.25 33 17.5 529 0.231 38.4 341 7.1 12.2 0.24 AM 7 2

[0551]

[0552] 50 0.21 31.6 16.6 525 0.193 35.5 365 6.9 11.5 0.25 9 2

[0553] 51 0.28 33.5 16.3 488 0.206 36.4 265 7.2 11 0.19 9

[0554]

[0555] Note: "-" denotes not available.

[0556] Example, Table 5. Summary of DSS intake (mL) of animals

[0557] Group Name A.No Day9 Day10 Day11 Day12 Day13 Day14 Day15 Disease Control 1 1.6 2.3 1.6 2.0 2.2 1.4 0.4

[0558] 2 1.6 2.3 1.6 2.0 2.2 1.4 0.4

[0559] 3 1.6 2.3 1.6 2.0 2.2 1.4 0.4

[0560] 4 1.6 2.3 1.6 2.0 2.2 1.4 0.4

[0561] 5 1.6 2.3 1.6 2.0 2.2 1.4 0.4

[0562] 6 1.6 2.3 1.6 2.0 2.2 1.4 0.4

[0563] 7 1.6 2.3 1.6 2.0 2.2 1.4 0.4

[0564]

[0565] 8 1.6 2.3 1.6 2.0 2.2 1.4 0.4

[0566]

[0567] FOS 9 2.3 2.7 1.4 1.6 1.7 2.0 1.7

[0568] 10 2.3 2.7 1.4 1.6 1.7 2.0 1.7

[0569] 11 2.3 2.7 1.4 1.6 1.7 2.0 1.7

[0570] 12 2.3 2.7 1.4 1.6 1.7 2.0 1.7

[0571] 13 2.3 2.7 1.4 1.6 1.7 2.0 1.7

[0572] 14 2.3 2.7 1.4 1.6 1.7 2.0 1.7

[0573] 15 2.3 2.7 1.4 1.6 1.7 2.0 1.7

[0574] 16 2.3 2.7 1.4 1.6 1.7 2.0 1.7

[0575] UT18 17 1.9 2.4 1.5 1.4 1.0 1.5 0.6

[0576] 18 1.9 2.4 1.5 1.4 1.0 1.5 0.6

[0577] 19 1.9 2.4 1.5 1.4 1.0 1.5 0.6

[0578] 20 1.9 2.4 1.5 1.4 1.0 1.5 0.6

[0579] 21 1.9 2.4 1.5 1.4 1.0 1.5 0.6

[0580] 22 1.9 2.4 1.5 1.4 1.0 1.5 0.6

[0581] 23 1.9 2.4 1.5 1.4 1.0 1.5 0.6

[0582]

[0583] 24 1.9 2.4 1.5 1.4 1.0 1.5 0.6

[0584]

[0585]

[0586] EP 25 1.8 2.3 2.4 2.1 2.0 1.7 1.6

[0587] 26 1.8 2.3 2.4 2.1 2.0 1.7 1.6

[0588] 27 1.8 2.3 2.4 2.1 2.0 1.7 1.6

[0589] 28 1.8 2.3 2.4 2.1 2.0 1.7 1.6

[0590] 29 1.8 2.3 2.4 2.1 2.0 1.7 1.6

[0591] 30 1.8 2.3 2.4 2.1 2.0 1.7 1.6

[0592] 31 1.8 2.3 2.4 2.1 2.0 1.7 1.6

[0593] 32 1.8 2.3 2.4 2.1 2.0 1.7 1.6

[0594] FOS+UT 18 33 1.9 2.4 2.0 2.3 1.8 1.4 2.0

[0595] 34 1.9 2.4 2.0 2.3 1.8 1.4 2.0

[0596] 35 1.9 2.4 2.0 2.3 1.8 1.4 2.0

[0597] 36 1.9 2.4 2.0 2.3 1.8 1.4 2.0

[0598] 37 1.9 2.4 2.0 2.3 1.8 1.4 2.0

[0599]

[0600] 38 1.9 2.4 2.0 2.3 1.8 1.4 2.0

[0601] 39 1.9 2.4 2.0 2.3 1.8 1.4 2.0

[0602] 40 1.9 2.4 2.0 2.3 1.8 1.4 2.0

[0603] FOS+UT 18 + EP 41 1.9 3.0 1.9 1.8 1.6 1.5 2.3

[0604] 42 1.9 3.0 1.9 1.8 1.6 1.5 2.3

[0605] 43 1.9 3.0 1.9 1.8 1.6 1.5 2.3

[0606] 44 1.9 3.0 1.9 1.8 1.6 1.5 2.3

[0607] 45 1.9 3.0 1.9 1.8 1.6 1.5 2.3

[0608] 46 1.9 3.0 1.9 1.8 1.6 1.5 2.3

[0609] 47 1.9 3.0 1.9 1.8 1.6 1.5 2.3

[0610] 48 1.9 3.0 1.9 1.8 1.6 1.5 2.3

[0611]

[0612] Table 6. Summary of Weight Loss Score of Animals

[0613] Group Name A. N Day Day Day Day Day Day Day Day 0 9 10 11 12 13 14 15 16

[0614] Disease control 1 0 0 1 0 0 2 3 4

[0615]

[0616] 2 0 0 1 0 1 2 3 4

[0617] 3 0 0 2 4 4 - - -

[0618] 4 0 0 0 0 0 1 3 4

[0619] 5 0 0 0 0 0 2 3 4

[0620] 6 0 0 2 4 4 - - -

[0621] 7 0 1 2 4 4 - - -

[0622]

[0623] 8 0 2 1 1 2 2 4 4

[0624] FOS 9 0 0 0 0 0 0 2 4

[0625] 10 0 0 0 0 0 0 1 3

[0626] 11 1 2 2 4 4 4 - -

[0627] 12 0 0 0 0 0 1 4 4

[0628] 13 - - - - - - - -

[0629] 14 0 0 0 0 2 3 4 4

[0630] 15 0 0 0 0 0 1 2 4

[0631]

[0632] 16 1 3 3 4 4 4 - -

[0633] UT18 17 0 0 0 0 0 0 1 3

[0634] 18 0 0 0 0 1 0 1 3

[0635] 19 0 0 0 0 0 1 1 2

[0636] 20 0 0 0 0 1 2 4 4

[0637] 21 0 0 0 0 0 1 3 4

[0638] 22 0 0 0 0 1 2 2 4

[0639] 23 0 0 0 0 0 0 0 2

[0640] 24 0 0 0 0 0 1 2 4

[0641]

[0642] EP 25 0 0 0 0 0 1 4 4

[0643] 26 1 2 3 4 4 4 - -

[0644] 27 0 2 2 3 4 4 4 4

[0645] 28 0 0 0 0 0 2 4 4

[0646] 29 0 0 0 0 1 3 4 4

[0647]

[0648] 30 0 0 0 0 1 1 1 3

[0649] 31 0 0 0 0 0 0 0 0

[0650] 32 0 2 2 4 4 3 4 4

[0651] FOS+UT 18 33 0 1 1 1 2 1 1 1

[0652] 34 0 0 0 0 1 3 4 -

[0653] 35 0 0 0 0 0 1 2 4

[0654] 36 0 0 0 0 0 0 0 1

[0655] 37 0 0 0 0 0 0 0 0

[0656] 38 0 0 0 0 0 0 0 3

[0657] 39 1 2 2 3 3 3 4 -

[0658] 40 0 0 0 0 1 3 4 4

[0659] FOS + UT 18+EP 41 0 0 0 2 1 1 2 2

[0660] 42 0 0 0 0 0 0 1 3

[0661] 43 0 0 1 0 1 2 4 -

[0662] 44 0 0 0 1 1 3 4 4

[0663]

[0664]

[0665] Example, Table 7. Summary of faecal haemoccult score of animals

[0666] Group Name A. N Day Day Day Day Day Day Day Day 0 9 10 11 12 13 14 15 16

[0667] Disease control 1 0 0 2 2 2 4 4 4

[0668] 2 0 0 2 2 2 4 4 4

[0669] 3 0 0 2 4 4 - -

[0670] 4 0 0 0 0 0 2 4 4

[0671] 5 0 0 0 0 0 2 3 4

[0672]

[0673] 6 0 2 4 4 4 - - -

[0674] 7 0 2 4 4 4 - - -

[0675] 8 0 2 2 2 4 4 4 4

[0676]

[0677] FOS 9 0 0 0 0 0 0 2 4

[0678] 10 0 0 0 0 0 0 2 4

[0679] 11 0 0 2 2 2 4 - -

[0680] 12 0 0 0 0 0 2 4 4

[0681] 13 - - - - - - - -

[0682] 14 0 0 0 0 2 4 4 4

[0683] 15 0 0 0 0 0 2 2 4

[0684] 16 2 4 4 4 4 4 - -

[0685] UT18 17 0 0 1 0 0 2 3 4

[0686] 18 0 0 1 0 1 2 3 4

[0687] 19 0 0 2 4 4 - - -

[0688] 20 0 0 0 0 0 1 3 4

[0689] 21 0 0 0 0 0 2 3 4

[0690] 22 0 0 2 4 4 - - -

[0691]

[0692] 23 0 1 2 4 4 - - -

[0693] 24 0 2 1 1 2 2 4 4

[0694] EP 25 0 0 0 0 0 0 2 4

[0695] 26 0 0 0 0 0 0 1 3

[0696] 27 1 2 2 4 4 4 - -

[0697] 28 0 0 0 0 0 1 4 4

[0698] 29 - - - - - - - -

[0699] 30 0 0 0 0 2 3 4 4

[0700] 31 0 0 0 0 0 1 2 4

[0701] 32 1 3 3 4 4 4 - -

[0702] FOS+UT 18 33 0 0 0 0 0 0 1 3

[0703] 34 0 0 0 0 1 0 1 3

[0704] 35 0 0 0 0 0 1 1 2

[0705] 36 0 0 0 0 1 2 4 4

[0706] 37 0 0 0 0 0 1 3 4

[0707]

[0708] 38 0 0 0 0 1 2 2 4

[0709] 39 0 0 0 0 0 0 0 2

[0710] 40 0 0 0 0 0 1 2 4

[0711] FOS+UT 18 +EP 41 0 0 0 0 0 1 4 4

[0712] 42 1 2 3 4 4 4 - -

[0713] 43 0 2 2 3 4 4 4 4

[0714] 44 0 0 0 0 0 2 4 4

[0715] 45 0 0 0 0 1 3 4 4

[0716] 46 0 0 0 0 1 1 1 3

[0717] 47 0 0 0 0 0 0 0 0

[0718] 48 0 2 2 4 4 3 4 4

[0719]

[0720] Note: "-" denotes not available.

[0721] DAI score Weight loss (%) Gross bleeding Stool condition

[0722] 0 None None Normal

[0723]

[0724] 1 1–5

[0725] 2 5–10 Hemoccult positive Loose

[0726] 3 10–20

[0727] 4 >20 Severe bleeding Diarrhea

[0728]

[0729] Example, Table 8. Summary of the disease activity index of animals

[0730] Group Name A. N Day Day Day Day Day Day Day Day 0 9 10 11 12 13 14 15 16

[0731] Disease control 1 0 0 2 1 1 3 4 4

[0732] 2 0 0 2 1 2 3 4 4

[0733] 3 0 0 2 4 4 - - -

[0734] 4 0 0 0 0 0 2 4 4

[0735] 5 0 0 0 0 0 2 3 4

[0736] 6 0 1 3 4 4 - - -

[0737] 7 0 2 3 4 4 - - -

[0738] 8 0 2 2 2 3 3 4 4

[0739]

[0740] FOS 9 0 0 0 0 0 0 2 4

[0741] 10 0 0 0 0 0 0 2 4

[0742] 11 0 1 2 3 3 4 - -

[0743] 12 0 0 0 0 0 2 4 4

[0744] 13 - - - - - - - -

[0745] 14 0 0 0 0 2 4 4 4

[0746] 15 0 0 0 0 0 2 2 4

[0747]

[0748] 16 2 4 4 4 4 4 - -

[0749] UT18 17 0 0 0 0 0 0 2 4

[0750] 18 0 0 0 0 2 0 2 4

[0751] 19 0 0 0 0 0 2 2 3

[0752] 20 0 0 0 0 2 2 4 4

[0753] 21 0 0 0 0 0 2 4 4

[0754] 22 0 0 0 0 2 2 2 4

[0755]

[0756] 23 0 0 0 0 0 0 0 2

[0757] 24 0 0 0 0 0 2 2 4

[0758] EP 25 0 0 0 0 0 2 4 4

[0759] 26 2 2 4 4 4 4 - -

[0760] 27 0 2 2 4 4 4 4 4

[0761] 28 0 0 0 0 0 2 4 4

[0762] 29 0 0 0 0 2 4 4 4

[0763] 30 0 0 0 0 2 2 2 4

[0764] 31 0 0 0 0 0 0 0 0

[0765] 32 0 2 2 4 4 4 4 4

[0766] FOS+UT 18 33 0 2 2 2 2 2 2 2

[0767] 34 0 0 0 0 2 4 4 -

[0768] 35 0 0 0 0 0 2 3 4

[0769] 36 0 0 0 0 0 0 0 2

[0770] 37 0 0 0 0 0 0 0 0

[0771]

[0772]

[0773] Note: "-" denotes not available.

[0774] DAI score Weight loss Gross bleeding Stool condition (%)

[0775] 0 None None Normal

[0776]

[0777] 1 1–5

[0778] 2 5–10 Hemoccult positive Loose

[0779] 3 10–20

[0780] 4 >20 Severe bleeding Diarrhea

[0781]

[0782] Example, Table 9. Summary of Serum Biochemistry Parameters of Animals

[0783] Group Name A. N ALP AST CHOL CREA GLU 0 (U / L) (U / L) (mg / dL) (mg / dL) (mg / dL)

[0784] Disease Control 1 284.44 142.16 0.38 0.08 148.65

[0785] 2 282.00 140.43 0.30 0.06 146.41

[0786] 3 - - - - -

[0787] 4 365.38 171.44 0.90 0.10 172.38

[0788] 5 351.19 168.71 0.11 0.11 166.99

[0789] 6 - - - - -

[0790] 7 - - - - -

[0791]

[0792] 8 360.96 219.50 0.04 0.10 132.88

[0793] FOS 9 192.82 171.27 14.88 0.11 104.01

[0794] 10 179.72 317.22 21.18 0.16 111.72

[0795] 11 - - - - -

[0796] 12 77.72 174.10 7.73 0.06 73.79

[0797] 13 - - - - -

[0798] 14 70.55 178.38 14.91 0.09 29.80

[0799] 15 382.13 234.70 0.90 0.10 141.80

[0800] 16 - - - - -

[0801] UT18 17 261.96 123.02 0.59 0.10 145.45

[0802] 18 261.14 123.17 0.20 0.09 143.16

[0803] 19 280.18 139.39 0.75 0.07 178.80

[0804] 20 278.24 138.78 0.65 0.09 175.09

[0805] 21 393.80 189.64 4.39 0.08 147.58

[0806] 22 409.39 193.57 4.75 0.09 151.09

[0807]

[0808] 23 257.51 194.52 0.55 0.11 142.99

[0809] 24 278.13 209.53 0.41 0.13 152.67

[0810]

[0811] EP 25 533.75 139.48 2.38 0.08 165.30

[0812] 26 - - - - -

[0813] 27 539.14 138.55 2.23 0.08 165.77

[0814] 28 240.47 177.59 3.77 0.08 121.84

[0815] 29 477.81 152.37 3.41 0.07 145.96

[0816] 30 330.16 225.43 1.57 0.10 174.35

[0817] 31 364.09 141.61 4.97 0.06 133.14

[0818] 32 321.55 200.85 1.75 0.09 149.28

[0819] FOS+UT 18 33 217.82 138.04 2.84 0.11 152.98

[0820] 34 - - - - -

[0821] 35 217.43 139.64 2.75 0.12 157.39

[0822] 36 395.41 124.32 1.77 0.10 243.53

[0823]

[0824] 37 347.75 165.36 8.90 0.07 195.04

[0825] 38 329.84 156.70 7.99 0.08 184.03

[0826] 39 - - - - -

[0827] 40 411.13 130.70 1.92 0.07 172.41

[0828] FOS+UT 18+EP 41 403.64 155.73 2.44 0.08 172.34

[0829] 42 368.20 196.13 2.36 0.07 152.89

[0830] 43 - - - - -

[0831] 44 363.88 108.72 6.86 0.07 134.22

[0832] 45 302.27 191.48 0.45 0.10 204.80

[0833] 46 298.85 191.59 3.70 0.11 120.13

[0834] 47 - - - - -

[0835] 48 349.32 127.23 4.44 0.08 120.11

[0836] SHAM 49 353.10 127.24 3.46 0.08 189.09

[0837] 50 335.36 149.01 3.69 0.09 189.87

[0838]

[0839] 51 350.76 150.16 3.64 0.08 166.76

[0840]

[0841]

[0842] Group Name A. N HDL LDL TBIL TGL BUN 0 (mg / dL) (mg / dL) (mg / dL) (mg / dL) (mg / dL)

[0843] Disease Control 1 48.69 39.98 0.11 0.09 16.84

[0844] 2 48.11 39.22 0.10 0.08 16.84

[0845] 3 - - - - -

[0846] 4 76.42 62.27 0.11 0.07 25.90

[0847] 5 75.20 60.83 0.11 0.07 25.48

[0848]

[0849] 6 - - - - -

[0850] 7 - - - - -

[0851] 8 62.30 54.62 0.09 0.14 23.54

[0852] FOS 9 62.72 65.06 0.12 0.09 18.59

[0853] 10 11.97 53.01 0.12 0.07 11.25

[0854] 11 - - - - -

[0855]

[0856] 12 105.20 101.55 0.15 0.10 29.00

[0857] 13 - - - - -

[0858] 14 107.00 106.89 0.08 0.06 23.30

[0859] 15 67.44 58.14 0.09 0.15 24.93

[0860] 16 - - - - -

[0861] UT18 17 52.06 45.07 0.13 0.08 23.66

[0862] 18 51.82 45.26 0.13 0.09 23.12

[0863] 19 65.94 58.49 0.08 0.08 20.64

[0864] 20 65.70 57.68 0.08 0.08 20.70

[0865] 21 54.65 47.57 0.09 0.11 25.05

[0866] 22 56.69 49.27 0.09 0.11 25.33

[0867]

[0868] 23 70.77 61.62 0.15 0.07 18.73

[0869] 24 77.79 66.51 0.15 0.07 19.96

[0870] EP 25 57.81 55.98 0.07 0.13 17.10

[0871]

[0872] 26 - - - - -

[0873] 27 57.65 55.82 0.07 0.13 16.68

[0874] 28 80.59 69.90 0.13 0.09 20.94

[0875] 29 58.85 53.00 0.10 0.08 19.84

[0876] 30 77.14 67.47 0.15 0.09 21.41

[0877] 31 66.09 54.70 0.12 0.08 15.82

[0878] 32 60.62 51.77 0.12 0.09 18.54

[0879] FOS+UT18 33 55.31 49.11 0.10 0.09 18.65

[0880] 34 - - - - -

[0881] 35 54.91 48.88 0.10 0.09 19.02

[0882] 36 57.58 47.29 0.09 0.08 22.93

[0883] 37 65.43 61.38 0.14 0.13 26.77

[0884] 38 61.13 57.57 0.14 0.12 25.48

[0885] 39 - - - - -

[0886] 40 64.60 54.54 0.09 0.09 19.01

[0887]

[0888] FOS+UT18+EP 41 61.70 52.10 0.09 0.10 17.84

[0889] 42 61.76 51.29 0.10 0.18 18.89

[0890] 43 - - - - -

[0891] 44 81.14 68.75 0.09 0.14 21.94

[0892] 45 63.64 53.11 0.10 0.18 17.88

[0893] 46 63.40 52.31 0.11 0.12 17.67

[0894] 47 - - - - -

[0895] 48 65.73 51.23 0.14 0.09 20.56

[0896] SHAM 49 66.62 51.87 0.14 0.10 21.10

[0897] 50 66.23 52.94 0.12 0.10 19.83

[0898] 51 69.62 56.79 0.10 0.10 20.34

[0899]

[0900] Note: "-" denotes not available.

[0901] Example, Table 10. Summary of Clinical Observations of Animals

[0902] Group A. Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Name No

[0903]

[0904] Disease 1 Normal Normal Normal Normal Normal Normal Normal Normal Control

[0905] 2 Normal Normal Normal Normal Normal Normal Normal Normal

[0906] 3 Normal Normal Normal Normal Normal Normal Normal Normal

[0907] 4 Normal Normal Normal Normal Normal Normal Normal Normal

[0908] 5 Normal Normal Normal Normal Normal Normal Normal Normal

[0909] 6 Normal Normal Normal Normal Normal Normal Normal Normal

[0910] 7 Normal Normal Normal Normal Normal Normal Normal Normal

[0911] 8 Normal Normal Normal Normal Normal Normal Normal Normal

[0912] FOS 9 Normal Normal Normal Normal Normal Normal Normal Normal

[0913] 10 Normal Normal Normal Normal Normal Normal Normal Normal

[0914] 11 Normal Normal Normal Normal Normal Normal Normal Dull

[0915] 12 Normal Normal Normal Normal Normal Normal Normal Normal

[0916] 13 — — — — — — — —

[0917] 14 Normal Normal Normal Normal Normal Normal Normal Normal

[0918]

[0919] 15 Normal Normal Normal Normal Normal Normal Normal Normal

[0920] 16 Normal Normal Normal Normal Normal Normal Normal Dull

[0921] UT18 17 Normal Normal Normal Normal Normal Normal Normal Normal

[0922] 18 Normal Normal Normal Normal Normal Normal Normal Normal

[0923]

[0924] 19 Normal Normal Normal Normal Normal Normal Normal Normal

[0925] 20 Normal Normal Normal Normal Normal Normal Normal Normal

[0926] 21 Normal Normal Normal Normal Normal Normal Normal Normal

[0927] 22 Normal Normal Normal Normal Normal Normal Normal Normal

[0928] 23 Normal Normal Normal Normal Normal Normal Normal Normal

[0929] 24 Normal Normal Normal Normal Normal Normal Normal Normal

[0930] EP 25 Normal Normal Normal Normal Normal Normal Normal Normal

[0931] 26 Normal Normal Normal Normal Normal Normal Normal Dull

[0932] 27 Normal Normal Normal Normal Normal Normal Normal Normal

[0933] 28 Normal Normal Normal Normal Normal Normal Normal Normal

[0934]

[0935] 29 Normal Normal Normal Normal Normal Normal Normal Normal

[0936] 30 Normal Normal Normal Normal Normal Normal Normal Normal

[0937] 31 Normal Normal Normal Normal Normal Normal Normal Dull

[0938] 32 Normal Normal Normal Normal Normal Normal Normal Dull

[0939] FOS + 33 Normal Dull Normal Normal Normal Normal Normal Normal UT18

[0940] 34 Normal Normal Normal Normal Normal Normal Normal Normal

[0941] 35 Normal Normal Normal Normal Normal Normal Normal Normal

[0942] 36 Normal Normal Normal Normal Normal Normal Normal Normal

[0943] 37 Normal Normal Normal Normal Normal Normal Normal Normal

[0944] 38 Normal Normal Normal Normal Normal Normal Normal Normal

[0945] 39 Normal Normal Normal Normal Normal Normal Normal Normal

[0946] 40 Normal Normal Normal Normal Normal Normal Normal Normal

[0947] FOS + 41 Normal Normal Normal Normal Normal Normal Normal Normal UT18 +

[0948] EP

[0949] 42 Normal Normal Normal Normal Normal Normal Normal Normal

[0950]

[0951] 43 Normal Normal Normal Normal Normal Normal Normal Normal

[0952] 44 Normal Normal Normal Normal Normal Normal Normal Normal

[0953] 45 Normal Dull Normal Normal Normal Normal Normal Normal

[0954] 46 Normal Normal Normal Normal Normal Normal Normal Normal

[0955] 47 Normal Normal Normal Normal Normal Normal Normal Normal

[0956] 48 Normal Normal Normal Normal Normal Normal Normal Normal

[0957] SHAM 49 Active Active Active Active Active Active Active Active

[0958] 50 Active Active Active Active Active Active Active Active

[0959] 51 Active Active Active Active Active Active Active Active

[0960]

[0961] Note: "-" denotes not available.

[0962] Group A. No Day 9 Day 10 Day 11 Day 12 Day 13 Day 14 Day 15 Name

[0963] Disease 1 Dull Dull Normal Normal Dull Normal Normal Control

[0964] 2 Normal Normal Dull Dull Dull Dull Dull

[0965] 3 Dull Dull Weak Morbid Normal Dead Dead

[0966]

[0967] 4 Dull Normal Normal Normal Dull Dull Normal

[0968] 5 Normal Normal Dull Dull Weak Dull Dull

[0969] 6 Dull Dull Weak Morbid Dead Dead Dead

[0970] 7 Normal Dull Weak Morbid Dead Dead Dead

[0971] 8 Normal Normal Dull Dull Normal Normal Dull

[0972] FOS 9 Normal Normal Normal Normal Normal Normal Normal

[0973] 10 Normal Normal Normal Normal Weak Weak Weak

[0974] 11 Normal Dull Weak Weak Weak Weak Dead

[0975] 12 Normal Normal Normal Normal Weak Weak Weak

[0976] 13 — — — — — — —

[0977] 14 Normal Normal Normal Weak Weak Weak Weak

[0978] 15 Normal Normal Normal Normal Normal Normal Normal

[0979]

[0980] 16 Dull Normal Weak Weak Weak Weak Dull

[0981] UT18 17 Normal Normal Normal Normal Normal Normal Normal

[0982]

[0983] 18 Normal Normal Normal Normal Normal Normal Normal

[0984] 19 Normal Normal Normal Normal Normal Normal Normal

[0985] 20 Normal Normal Normal Normal Normal Normal Normal

[0986] 21 Normal Normal Normal Dull Weak Weak Weak

[0987] 22 Normal Normal Normal Normal Normal Normal Normal

[0988] 23 Normal Normal Normal Normal Normal Dull Dull

[0989] 24 Normal Normal Normal Dull Dull Normal Normal

[0990] EP 25 Normal Normal Normal Normal Normal Dull Dull

[0991] 26 Dull Dull Weak Dull Dull Weak Dead

[0992] 27 Normal Normal Normal Normal Weak Weak Weak

[0993] 28 Normal Normal Normal Dull Dull Normal Normal

[0994] 29 Normal Normal Normal Dull Dull Normal Normal

[0995] 30 Normal Normal Normal Normal Normal Dull Dull

[0996] 31 Dull Normal Normal Normal Normal Normal Normal

[0997] 32 Dull Normal Weak Weak Weak Weak Weak

[0998]

[0999] FOS + 33 Dull Dull Weak Dull Dull Normal Normal UT18

[1000] 34 Normal Dull Normal Normal Weak Weak Morbid

[1001] 35 Normal Normal Normal Dull Dull Normal Normal

[1002] 36 Normal Normal Normal Normal Dull Dull Normal

[1003] 37 Normal Normal Normal Normal Normal Normal Normal

[1004] 38 Normal Normal Normal Normal Normal Normal Normal

[1005] 39 Dull Dull Weak Normal Weak Weak Morbid

[1006] 40 Normal Normal Normal Normal Weak Weak Weak

[1007] FOS + 41 Normal Dull Normal Weak Weak Weak Weak UT18+

[1008] EP 42 Normal Normal Normal Normal Normal Normal Normal

[1009] 43 Normal Dull Normal Weak Weak Weak Morbid

[1010] 44 Normal Normal Normal Normal Dull Dull Normal

[1011] 45 Normal Normal Normal Normal Normal Dull Dull

[1012] 46 Normal Normal Normal Normal Normal Normal Normal

[1013]

[1014] 47 Normal Normal Weak Weak Weak Weak Morbid

[1015] 48 Normal Normal Normal Weak Normal Normal Normal

[1016] SHAM 49 Active Active Active Active Active Active Active

[1017] 50 Active Active Active Active Active Active Active

[1018] 51 Active Active Active Active Active Active Active

[1019]

[1020] Example, Table 11. Summary of Vital Organ Weights(g) of Animals

[1021] Group A. Liver Spleen Kidney Lung Hear Teste Brain Colo Colo Name No s (g) t(g) s (g)

[1022] (g) (g) (g) (g) n n weig lengt ht (g) h (cm)

[1023] Disease 1 0.84 0.11 0.33 0.22 0.18 0.26 0.42 0.25 7 control

[1024] 2 0.90 0.08 0.29 0.13 0.12 0.20 0.40 0.37 6.6

[1025] 3 - - - - - - - - -

[1026] 4 0.72 0.04 0.23 0.17 0.09 0.22 0.40 0.29 6.9

[1027] 5 0.70 0.07 0.28 0.15 0.09 0.22 0.37 0.30 6.7

[1028] 6 - - - - - - - - -

[1029]

[1030] 7 - - - - - - - - -

[1031] 8 0.81 0.11 0.29 0.37 0.10 0.22 0.34 0.27 5.5

[1032] FOS 9 1.12 0.12 0.34 0.25 0.10 0.16 0.05 0.44 7

[1033] 10 1.47 0.31 0.46 0.26 0.16 0.20 0.45 0.23 8

[1034] 11 - - - - - - - - -

[1035]

[1036] 12 0.95 0.20 0.30 0.21 0.12 0.19 0.44 0.22 7.6

[1037] 13 - - - - - - - - -

[1038] 14 0.91 0.13 0.22 0.20 0.10 0.20 0.33 0.14 8

[1039] 15 0.96 0.11 0.30 0.16 0.11 0.20 0.37 0.38 7.6

[1040] 16 - - - - - - - - -

[1041] UT18 17 0.76 0.11 0.21 0.16 0.10 0.16 0.36 0.38 6.5

[1042] 18 0.92 0.06 0.30 0.13 0.12 0.22 0.41 0.26 6.7

[1043] 19 10.20 0.10 0.36 0.17 0.12 0.22 0.44 0.43 8.6

[1044] 20 0.87 0.08 0.31 0.19 0.11 0.25 0.40 0.30 6.5

[1045]

[1046] 21 0.65 0.05 0.25 0.14 0.09 0.19 0.41 0.17 5.7

[1047] 22 0.83 0.09 0.28 0.15 0.09 0.21 0.36 0.30 6

[1048] 23 0.98 0.09 0.25 0.18 0.11 0.20 0.37 0.37 6.6

[1049] 24 0.81 0.07 0.24 0.18 0.10 0.20 0.41 0.23 6.3

[1050] EP 25 1.07 0.05 0.29 0.17 0.13 0.09 0.41 0.21 6.7

[1051] 26 - - - - - - - - -

[1052] 27 0.74 0.04 0.40 0.22 0.11 0.17 0.41 0.13 7.6

[1053] 28 1.01 0.10 0.33 0.26 0.13 0.18 0.41 0.20 5.5

[1054]

[1055] 29 0.87 0.10 0.35 0.10 0.09 0.19 0.43 0.17 8.3

[1056] 30 1.15 0.13 0.27 0.15 0.09 0.09 37.00 0.39 8

[1057] 31 1.14 0.05 0.29 0.19 0.11 0.17 0.30 0.30 7.1

[1058] 32 0.77 0.05 0.28 0.06 0.10 0.18 0.36 0.11 7.5

[1059] FOS+U 33 0.82 0.09 0.27 0.18 0.12 0.22 0.43 0.19 7.5 T18

[1060] 34 0.59 0.04 0.27 0.03 0.02 0.09 0.27 0.17 7

[1061]

[1062] 35 1.17 0.16 0.20 0.21 0.15 0.20 0.27 0.16 6.7

[1063] 36 0.99 0.16 0.31 0.22 0.13 0.23 0.41 0.21 6.8

[1064] 37 0.93 0.10 0.27 0.17 0.13 0.20 0.31 0.10 6.5

[1065] 38 0.95 0.18 0.53 0.21 0.14 0.21 0.44 0.15 5.4

[1066] 39 0.74 0.04 0.26 0.17 0.13 0.20 0.31 0.10 6.5

[1067] 40 0.88 0.07 0.31 0.18 0.13 0.18 0.40 0.34 7.4

[1068] FOS+U 41 0.80 0.09 0.24 0.20 0.10 0.20 0.39 0.18 8 T18+E

[1069] P 42 0.84 0.16 0.30 0.13 0.13 0.21 0.43 0.22 8.6

[1070] 43 - - - - - - - - -

[1071] 44 0.99 0.10 0.28 0.17 0.15 0.24 0.41 0.19 7.3

[1072] 45 0.92 0.09 0.48 0.18 0.12 0.14 0.40 0.31 5.1

[1073] 46 1.19 0.08 0.30 0.14 0.13 0.02 0.32 0.27 7

[1074] 47 - - - - - - - - -

[1075] 48 0.89 0.08 0.30 0.17 0.10 0.21 0.41 0.34 7.7

[1076] SHAM 49 1.02 - - - - - - 0.49 7.3

[1077]

[1078] 50 1.04 - - - - - - 0.63 8.2

[1079] 51 0.95 - - - - - - 0.44 6.7

[1080]

[1081] Note: “■ ■” denotes not available.

[1082] *Kidneys, Testes, and Ovaries were collected and weighed as pairs.

[1083] Example, Table 12. Summary of Colon Histopathology

[1084] Group Animal No. Inflammation Crypt Ulceration Oedema damage

[1085] Disease 1 ++ ++ + - control

[1086] 2 ++ + + -

[1087] 3 + ++++ ++

[1088] 4 +++ +++ + +

[1089] 5 +++ +++ ++ +

[1090] 6 + - + -

[1091] 7 Tissue not intact

[1092]

[1093] 8 +++ +++ ++ +

[1094]

[1095] FOS 9 ++ ++ + +

[1096] 10 ++++ ++++ +++ -

[1097] 11 Tissue not intact

[1098] 12 ++ ++ ++ +

[1099] 13 Tissue not

[1100] present

[1101] 14 + + + -

[1102] 15 ++++ +++ +++ +

[1103] 16 + + + -

[1104] UT18 17 +++ ++ ++ -

[1105] 18 +++ +++ ++ +

[1106] 19 ++ ++ + -

[1107] 20 + - - -

[1108] 21 +++ ++++ ++ +

[1109] 22 ++ +++ + -

[1110]

[1111] 23 + + - -

[1112] 24 + ++ - -

[1113]

[1114] EP 25 +++ +++ ++ +

[1115] 26 ++ ++++ ++ +

[1116] 27 ++ +++ ++ -

[1117] 28 ++ ++ - -

[1118] 29 +++ +++ +++ +

[1119] 30 - - - -

[1120] 31 - + - -

[1121] 32 + + - -

[1122] F0S+UT18 33 + ++ - -

[1123] 34 + ++++ +++ -

[1124] 35 + + - -

[1125] 36 +++ +++ + +

[1126]

[1127] 37 +++ +++ + +

[1128] 38 +++ ++++ + +

[1129] 39 ++ +++ +++ +

[1130] 40 + + - -

[1131] F0S+UT18+E 41 + + - -

[1132] P 42 + + - -

[1133] 43 - +++ +++ +

[1134] 44 ++ ++ - -

[1135] 45 + + - -

[1136] 46 +++ ++ + +

[1137] 47 ++ +++ ++ +

[1138] 48 ++ + + -

[1139] SHAM 49 - - - -

[1140] 50 - - - -

[1141] 51 - - - -

[1142]

[1143] Note:-: absent

[1144] +: Mild

[1145] ++: Moderate

[1146] +++: Marked

[1147] ++++: Severe

[1148] Example, Table 13. Summary of Liver Histopathology

[1149] Group Details Animal Observations

[1150] No.

[1151]

[1152] Disease control 1 No abnormalities observed, normal hepatic architecture observed

[1153] 2 No abnormalities observed, normal hepatic architecture observed

[1154] 3 Tissue not present

[1155] 4 No abnormalities observed, normal hepatic architecture observed

[1156] 5 No abnormalities observed, normal hepatic architecture observed

[1157] 6 Tissue not present

[1158] 7 Tissue not present

[1159]

[1160] No abnormalities observed, normal hepatic architecture observed

[1161] No abnormalities observed, normal hepatic architecture observed

[1162] No abnormalities observed, normal hepatic architecture observed

[1163] Tissue not present

[1164] No abnormalities observed, normal hepatic architecture observed

[1165] Tissue not present

[1166]

[1167] No abnormalities observed, normal hepatic architecture observed

[1168] No abnormalities observed, normal hepatic architecture observed

[1169] Tissue not present

[1170] No abnormalities observed, normal hepatic architecture observed

[1171] No abnormalities observed, normal hepatic architecture observed

[1172]

[1173]

[1174] No abnormalities observed, normal hepatic architecture observed

[1175] No abnormalities observed, normal hepatic architecture observed

[1176] No abnormalities observed, normal hepatic architecture observed

[1177] No abnormalities observed, normal hepatic architecture observed

[1178] No abnormalities observed, normal hepatic architecture observed

[1179] No abnormalities observed, normal hepatic architecture observed

[1180] No abnormalities observed, normal hepatic architecture observed

[1181]

[1182] Tissue not present

[1183] No abnormalities observed, normal hepatic architecture observed

[1184] No abnormalities observed, normal hepatic architecture observed

[1185] No abnormalities observed, normal hepatic architecture observed

[1186]

[1187]

[1188] 30 No abnormalities observed, normal hepatic architecture observed

[1189] 31 No abnormalities observed, normal hepatic architecture observed

[1190] 32 No abnormalities observed, normal hepatic architecture observed

[1191] 33 No abnormalities observed, normal hepatic architecture observed

[1192] F0S+UT18 34 Tissue not present

[1193] 35 No abnormalities observed, normal hepatic architecture observed

[1194] 36 No abnormalities observed, normal hepatic architecture observed

[1195] 37 No abnormalities observed, normal hepatic architecture observed

[1196]

[1197] 38 No abnormalities observed, normal hepatic architecture observed

[1198] 39 Tissue not present

[1199] 40 No abnormalities observed, normal hepatic architecture observed

[1200]

[1201] FOS+UT18+EP 41 No abnormalities observed, normal hepatic architecture observed

[1202] 42 No abnormalities observed, normal hepatic architecture observed

[1203] 43 Tissue not present

[1204] 44 No abnormalities observed, normal hepatic architecture observed

[1205] 45 No abnormalities observed, normal hepatic architecture observed

[1206] 46 No abnormalities observed, normal hepatic architecture observed

[1207] 47 No abnormalities observed, normal hepatic architecture observed

[1208] 48 No abnormalities observed, normal hepatic architecture observed

[1209] SHAM 49 No abnormalities observed, normal hepatic architecture observed

[1210] 50 No abnormalities observed, normal hepatic architecture observed

[1211] 51 No abnormalities observed, normal hepatic architecture observed

[1212]

[1213] The DSS colitis study (Study No. CB / 2025 / WTFABA / 024) showed:

[1214] - Body weight ranking: FOS+UT 18 > EP > FOS > UT 18 > FOS+UT 18+EP > Disease Control. - DAI ranking: FOS+UT 18 > EP > FOS+UT 18+EP > UT 18 > FOS > Disease Control.

[1215] - Colon length preservation: FOS+UT 18+EP > FOS > EP > FOS+UT 18 > UT 18 > Disease Control. - Histopathology: EP > FOS+UT 18+EP > FOS+UT 18 > UT 18 > FOS > Disease Control.

[1216] The formulation can be presented in oral liquids, sachets, gummies, or capsules. A preferred packaging uses a two-component kit: EP in a liquid phase and FOS+UT 18 as a dry blend, reconstituted before use

[1217] This invention provides a novel synergistic nutraceutical formulation aimed at the prevention, dietary management, and symptom reduction of inflammatory bowel disease (IBD), including conditions such as colitis and ulcerative colitis. The formulation uniquely integrates three bioactive components — Fructooligosaccharide (FOS), UT 18, and enhancer protein — each contributing distinct physiological benefits that, when combined, produce enhanced therapeutic effects. FOS, present in the range of 5-10% w / v with a degree of polymerization between three and five, serves as a prebiotic that promotes the growth of beneficial gut microbiota and stimulates butyrate production, a key short-chain fatty acid associated with colon health. UT 18 is an amino acid-organic acid blend containing arginine (26.13 mg), glycine (11.26 mg), and citric acid (28.81 mg), known for its anti-inflammatory action and ability to support gut barrier repair. EP, extracted, purified, and lyophilized from enhancer protein, provides potent antioxidant and wound-healing properties that further strengthen intestinal integrity.

[1218] The synergy between FOS, UT 18, and EP results in enhanced gut-protective and antiinflammatory effects compared to the use of the individual ingredients in isolation. Notably, the formulation produces a minimum of 15% higher butyrate production by human gut microbiota compared to FOS alone, thereby improving gut microbial metabolism. When EP is combined with FOS, reactive oxygen species (ROS) levels in colonic epithelial cells are reduced by at least 10% more than with either ingredient used separately, indicating a stronger antioxidant effect. Furthermore, in Caco-2 scratch assays, the combination of UT 18 and EP accelerates wound closure by approximately1.2 times compared to the rate achieved by each component alone, demonstrating a tangible advantage in epithelial repair.

[1219] The composition can be produced in multiple delivery forms, including liquid suspensions, dry powders, granules, sachets, capsules, or effervescent tablets, making it adaptable for varied consumer preferences and clinical needs. To maintain stability and bioactivity, the pH of the formulation is adjusted between 6.8 and 7.4, and blending is performed under an inert nitrogen atmosphere to prevent oxidative degradation. Carriers such as water, isotonic saline, glycerol, maltodextrin, or their combinations can be used to optimize solubility, taste, and shelf-life. The formulation’s weight ratio of FOS to UT 18 to EP is maintained within the range of 2: 1: 1 to 4:2: 1 to ensure the intended synergistic effect and optimal functional performance.

[1220] The manufacturing process begins by dissolving EP in phosphate-buffered saline at pH 7.2 to achieve a stable solubilized form. This is followed by blending with FOS to allow uniform dispersion of the prebiotic component. UT 18 is then incorporated under continuous mixing to ensure even distribution of its amino acid-organic acid content. The entire mixture is subsequently homogenized under nitrogen to safeguard sensitive components against oxidative damage. Once homogenized, the formulation is processed into the selected dosage form according to intended use and target market requirements.

[1221] An innovative packaging concept is also proposed to further extend product stability and convenience. The system consists of a dual-container arrangement where the first container holds the solubilized EP, while the second container contains the dry blend of FOS and UT 18. This separation prevents premature interaction between components that may lead to degradation. The package includes clear instructions for reconstitution, ensuring that the user can easily prepare the oral formulation immediately before consumption, thereby maximizing potency.

[1222] This nutraceutical formulation has a broad range of applications, including use in functional foods, dietary supplements, and nutraceutical beverages. Its natural-source ingredients make it safe, nontoxic, and suitable for long-term consumption without significant side effects. By maintaining gut integrity, reducing inflammation, and alleviating discomfort associated with IBD, the product provides a sustainable, consumer-friendly dietary intervention. Its mechanism of action — through microbiotamodulation, oxidative stress reduction, and gut barrier restoration — offers a holistic approach that goes beyond symptomatic relief to address the underlying contributors to IBD progression.

[1223] The impact of this invention is significant for individuals at risk of or already affected by inflammatory bowel disease. With its scientifically validated performance, stable formulation, and convenient delivery options, it represents a forward-thinking, sustainable approach to gastrointestinal health management. By combining prebiotic stimulation, amino acid-based gut repair, and antioxidant protection into a single synergistic product, the invention stands to improve the quality of life for millions of people while reducing reliance on long-term pharmaceutical interventions.

Claims

We Claim:

1. A nutraceutical composition, comprising:(a) fructooligosaccharide (FOS) present in an amount of 5-90% w / v; and(b) a defined amino acid-organic acid blend (UT-18) comprising arginine, glycine, and citric acid; wherein the composition is formulated in a nutraceutically acceptable carrier having a pH in the range of 6.8 to 7.4, and wherein the combination of FOS and UT-18 exhibits a synergistic effect in reducing inflammatory markers and improving colonic epithelial integrity, as compared to administration of FOS or UT-18 individually.2 The nutraceutical composition as claimed in claim 1, wherein the UT-18 blend comprises: arginine in an amount of 26.13 mg, glycine in an amount of 11.26 mg, and citric acid in an amount of 28.81 mg, per unit formulation.

3. The nutraceutical composition as claimed in claim 1 or claim 2, further comprising an enhancer protein (EP), wherein the enhancer protein is a proteinaceous composition having antioxidant and anti¬ inflammatory activity and a purity of at least 90%.

4. The nutraceutical composition as claimed in claim 3, wherein the enhancer protein is present in an amount effective to promote epithelial repair while maintaining the synergistic activity of the FOS and UT-18 combination.5 The nutraceutical composition as claimed in any one of the preceding claims, wherein the nutraceutically acceptable carrier is selected from water, phosphate-buffered saline, glycerol, maltodextrin, or combinations thereof.

6. The nutraceutical composition as claimed in any one of the preceding claims, wherein the composition is formulated as a liquid oral formulation, powder, sachet, capsule, tablet, gummy, or effervescent dosage form.

7. The nutraceutical composition as claimed in any one of the preceding claims, useful as a nutraceutical formulation for supporting gastrointestinal health and for prevention or amelioration of inflammatory conditions of the gastrointestinal tract, including inflammatory bowel disease, ulcerative colitis, irritable bowel syndrome, radiation-induced mucositis, and post-surgical gastrointestinal recovery.

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