WO2024123075A1 - Composition pour améliorer la fonction intestinale en utilisant un extrait de navet - Google Patents
Composition pour améliorer la fonction intestinale en utilisant un extrait de navet Download PDFInfo
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- WO2024123075A1 WO2024123075A1 PCT/KR2023/019990 KR2023019990W WO2024123075A1 WO 2024123075 A1 WO2024123075 A1 WO 2024123075A1 KR 2023019990 W KR2023019990 W KR 2023019990W WO 2024123075 A1 WO2024123075 A1 WO 2024123075A1
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- intestinal
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Images
Definitions
- the present invention relates to a composition for improving intestinal function using turnip ( Brassica Rapa . L. or B. Rapa horenisis . L) extract.
- the intestinal tract wall is structurally composed of intestinal epithelial cells, mucus layer, and various substrates.
- the epithelial cell layer has selective permeability to nutrients, electrolytes, and moisture and functions as a biochemical barrier, as well as a physical barrier that protects against intestinal toxins, antigens, and intestinal microorganisms.
- the intestinal mucosa layer physically separates the intestinal epithelium from harmful compounds, enzymes, and microorganisms introduced into the luminal environment of the intestine, forming a primary barrier against harmful substances and promoting smooth movement of food entering the intestine.
- the intestinal mucosal layer is mainly composed of mucin, a glycoprotein, and this mucin glycoprotein forms the gel of the mucosal layer.
- MUC2 mucin is an important component of the mucosal layer and plays a critical role in protecting the intestinal epithelium and maintaining intestinal homeostasis (International Journal of Biological Macromolecules 164 (2020) 884-891).
- MUC2 mucin is deficient, the composition of the mucous membrane changes. Inflammatory bowel disease occurs, and in ulcerative colitis, it is known that less MUC2 mucin is secreted, resulting in thin and discontinuous mucous membranes (Oncotarget 8 (2017) 71456-71470).
- the route by which substances are absorbed in the small intestine includes a selective permeation route through epithelial cells (transcellular pathway) and a paracellular pathway through tight junctions, which are junctions between epithelial cells. Substances with low molecular weight pass through the intestinal wall through tight junctions, which are gaps between epithelial cells.
- Tight junctions are a network of proteins between epithelial cells, and these proteins include integral transmembrane proteins such as occludin, claudin, and junctional adhesion molecules, and ZO. It is broadly classified into plaque proteins such as -1 (zonula occludens proteins-1). The intrinsic transmembrane protein uses ZO-1 (zona occludens-1) and cingulin, which are plate proteins present in the cytoplasm, as mediators, to actin, a cytoskeletal muscle, and a number of cytosolic regulatory proteins. ), and performs a biological barrier function that regulates adhesion between cells and the movement of substances through the space around cells.
- ZO-1 zona occludens-1
- cingulin cingulin
- ZO-1 an occludin protein such as the plate protein, is composed of multiple domains and is known to play an essential role in regulating the permeability of the intestinal wall by binding to various junction proteins (Mol Biol Cell. 2006 Apr; 17( 4): 1922-1932, Ann N Y Acad Sci. 2022 Aug;1514(1):21-33;2021 Dec;161(6):1924-1939).
- GALT Gut-associated lymphatic tissue
- Peyer's patch a characteristic tissue of GALT, is a tissue that is easily observed with the naked eye and is distributed throughout the small intestine and is concentrated in the ileum of the small intestine.
- Peyer's patch is an inducing site for IgA production and is composed of T cells, B cells, macrophages, dendritic cells, etc. Additionally, M cells (micro enfold cells), which are antigen-sampling cells, are present in the intestinal tract. Acts as a key lymphoid organ (J Immunol 180: 1293-1294, 2008; J Dairy Sci 86: 3321-3329, 2003).
- M cells present in Peyer's patches activate immune cells by ingesting soluble antigens, bacteria, or viruses from the intestinal lumen through pinocytosis or phagocytosis and moving them to lymphoid cells (Proc Natl Acad Sci USA 101: 6110-6115, 2004; FEMS Immunol Med Microbiol 52: 2-12, 2008). These activated immune cells and the cytokines produced and secreted by these immune cells are called mesenteric lymph nodes. It regulates not only intestinal immunity but also systemic immunity by regulating the growth, migration, and differentiation of circulating immune system or hematopoietic cells such as bone marrow cells and white blood cells through the thoracic duct (J Immunol 176: 7533-7541, 2006)
- the present invention discloses the intestinal function improving activity of a turnip extract, particularly the intestinal barrier function improving activity and the intestinal immune function improving activity.
- the purpose of the present invention is to provide a composition for improving intestinal function using turnip extract.
- Another object of the present invention is to provide a composition for improving intestinal barrier function using turnip extract.
- Another object of the present invention is to provide a composition for improving intestinal immune function using turnip extract.
- the present invention promotes the expression of MUC2, a major mucin protein in the intestinal (small intestine and/or large intestine) mucosal layer, in LS174T cells, a colon cancer cell line, while the turnip extract does not show any particular cytotoxicity, , promotes the expression of ZO-1, a major protein of intestinal tight junctions, in Caco2 cells, a colon cancer cell line, and also increases the number of lymphocytes in the blood in animal experiments, promotes the production of IgA in the small intestine, and promotes the production of GM-CSF (Granulocyte) in Peyer's patches. It was completed by confirming that it increased the expression of the -macrophage colony-stimulating factor) gene and increased the size and number of lymphocytic follicular compartments in Peyer's patches.
- the present invention is provided based on these experimental results.
- the present invention can be viewed as a composition for improving intestinal function containing turnip extract as an active ingredient
- the present invention can be viewed as a composition for improving intestinal function containing turnip extract as an active ingredient. It can be viewed as a composition for improving function, and in another aspect, it can be viewed as a composition for improving intestinal immune function containing turnip extract as an active ingredient, and in another aspect, it can be seen as a composition for improving intestinal barrier function containing turnip extract as an active ingredient. It can be identified as a composition for preventing or treating diseases according to.
- extract refers to the stem, leaf, fruit, flower, root, etc. of the plant to be extracted, mixed with water, lower alcohol with 1 to 4 carbon atoms (methanol, ethanol, butanol, etc.), methylene chloride, ethylene, acetone, hexane, Extract obtained by leaching using ether, chloroform, ethyl acetate, butylacetate, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol, or mixed solvents thereof.
- a supercritical extraction solvent such as carbon dioxide or pentane, or a fraction obtained by fractionating the extract.
- the extraction method is cold immersion, reflux, heating, and ultrasonic radiation, taking into account the polarity of the active substance, degree of extraction, and degree of preservation. , any method such as supercritical extraction can be applied.
- a fractionated extract the extract is suspended in a specific solvent and then mixed with a solvent of different polarity to form a fraction obtained by adsorbing the crude extract onto a column filled with silica gel and then mixed with a hydrophobic solvent, a hydrophilic solvent, or a mixture of these. It is meant to include fractions obtained using the mobile phase.
- the meaning of the extract includes concentrated liquid extract or solid extract from which the extraction solvent has been removed by methods such as freeze-drying, vacuum drying, hot air drying, and spray drying. Preferably, it refers to an extract obtained using water, ethanol, or a mixed solvent thereof as an extraction solvent.
- improved of intestinal function means improvement of intestinal barrier function and/or improvement of intestinal immune function.
- “improving intestinal barrier function” means strengthening the intestinal mucosa layer and/or improving the barrier function of intestinal tight junctions.
- disease caused by impaired intestinal barrier function refers to a disease caused by impaired intestinal barrier function, that is, destruction of the intestinal mucosa layer and/or impaired barrier function of intestinal tight junctions, such as leaky gut syndrome, endotoxemia, and inflammation. refers to inflammatory bowel disease and/or ulcerative colitis.
- active ingredient refers to an ingredient that exhibits the desired activity alone or can exhibit activity in combination with a carrier that is not active on its own.
- the composition of the present invention may contain the active ingredient in any amount (effective amount) depending on the use, formulation, purpose of mixing, etc., as long as it can exhibit intestinal function improvement activity, etc., and a typical effective amount is based on the total weight of the composition. It will be determined within the range of 0.001% by weight to 20.0% by weight.
- “effective amount” means that when the composition of the present invention is administered to mammals, preferably humans, to which it is applied during the administration period recommended by medical experts, etc., it can exhibit the intended functional and pharmacological effects, such as improvement of intestinal function. It refers to the amount of active ingredient contained in the composition of the present invention. Such effective amounts can be determined experimentally within the scope of the ordinary ability of those skilled in the art.
- the composition of the present invention has already been verified for safety in the art in order to enhance and reinforce the effect of improving intestinal function or to improve the convenience of taking or ingesting through the addition of similar activities such as improving gastric function. It may further include any compounds or natural extracts known to have activity. These compounds or extracts include compounds, extracts, and pharmaceuticals listed in compendial documents such as the Pharmacopoeia of each country (in Korea, the “Korean Pharmacopoeia”) and the Code of Health Functional Foods of each country (in Korea, it is the “Standards and Specifications for Health Functional Foods” notified by the Ministry of Food and Drug Safety).
- composition of the present invention can be considered a food composition.
- the food composition of the present invention can be manufactured in any form, for example, beverages such as tea, juice, carbonated beverages, and electrolyte drinks, processed oils such as milk and yogurt, gums, rice cakes, Korean snacks, bread, snacks, noodles, etc. It can be manufactured into health functional food preparations such as foods, tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars, etc.
- beverages such as tea, juice, carbonated beverages, and electrolyte drinks
- processed oils such as milk and yogurt, gums, rice cakes, Korean snacks, bread, snacks, noodles, etc.
- health functional food preparations such as foods, tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars, etc.
- the food composition of the present invention can have any product classification in terms of legal and functional classification as long as it complies with the enforcement laws and regulations at the time of manufacture and distribution.
- it is a health functional food according to the Korean ⁇ Act on Health Functional Foods ⁇ , or confectionery, beans, tea, and beverages according to each food type according to the food code of the Korean ⁇ Food Sanitation Act ⁇ (Ministry of Food and Drug Safety Notification ⁇ Food Standards and Specifications ⁇ ) , special purpose food, etc.
- the food composition of the present invention may contain food additives in addition to the active ingredients.
- Food additives can generally be understood as substances that are added to, mixed with, or infiltrated into food when manufacturing, processing, or preserving food. Since they are consumed daily and for a long period of time with food, their safety must be guaranteed.
- food additive code of each country that regulates the manufacturing and distribution of food in Korea, it is the Food Sanitation Act
- food additives with guaranteed safety are limited in terms of ingredients or functions.
- food additives are classified into chemical synthetics, natural additives, and mixed preparations in terms of composition. These food additives are classified into sweeteners and flavors in terms of function. It is classified into preservatives, emulsifiers, acidulants, thickeners, etc.
- Sweeteners are used to impart an appropriate sweetness to foods, and both natural and synthetic ones can be used in the food composition of the present invention.
- a natural sweetener is used, and natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose, and maltose.
- Flavoring agents are used to improve taste or aroma, and both natural and synthetic ones can be used.
- natural products are used. When using natural products, it can serve the purpose of enhancing nutrition in addition to flavor.
- Natural flavoring agents may be obtained from apples, lemons, tangerines, grapes, strawberries, peaches, etc., or may be obtained from green tea leaves, coriander leaves, bamboo leaves, cinnamon, chrysanthemum leaves, jasmine, etc. You can also use things obtained from ginseng (red ginseng), bamboo shoots, aloe vera, and ginkgo nuts. Natural flavors can be liquid concentrates or solid extracts.
- synthetic flavoring agents may be used, and as synthetic flavoring agents, esters, alcohols, aldehydes, terpenes, etc. may be used.
- Preservatives include calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc.
- emulsifiers include acacia gum, carboxymethyl cellulose, xanthan gum, and pectin. etc. may be used, and as acidulants, acidic acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, etc. may be used.
- acidulants may be added to ensure that the food composition has an appropriate acidity for the purpose of suppressing the growth of microorganisms.
- a thickening agent a suspending agent, settling agent, gel forming agent, bulking agent, etc. may be used.
- the food composition of the present invention may contain bioactive substances or minerals known in the art and whose safety is guaranteed as food additives for the purpose of supplementing and reinforcing functionality and nutrition.
- physiologically active substances include catechins contained in green tea, vitamins such as vitamin B1, vitamin C, vitamin E, and vitamin B12, tocopherol, dibenzoylthiamine, etc.
- minerals include calcium preparations such as calcium citrate and magnesium stearate.
- Magnesium preparations such as iron citrate, iron preparations such as chromium chloride, potassium iodine, selenium, germanium, vanadium, zinc, etc. are included.
- the food composition of the present invention may contain the above-described food additives in an appropriate amount to achieve the purpose of addition depending on the product type.
- each country's food code or food additive code can be referred to.
- composition of the present invention may be considered a pharmaceutical composition in other specific embodiments.
- the pharmaceutical composition of the present invention contains a pharmaceutically acceptable carrier in addition to the active ingredient and can be prepared into an oral formulation or a parenteral formulation depending on the route of administration by a conventional method known in the art.
- the route of administration may be any suitable route, including topical route, oral route, intravenous route, intramuscular route, and direct absorption through mucosal tissue, and two or more routes may be used in combination.
- Pharmaceutically acceptable carriers are well known in the art depending on the route of administration or dosage form, and for specifics, reference can be made to the pharmacopoeia of each country, including the “Korean Pharmacopoeia.”
- the pharmaceutical composition of the present invention when prepared as an oral dosage form, it can be prepared as powder, granules, tablets, pills, sugar-coated tablets, capsules, solutions, gels, syrups, suspensions, and wafers along with a suitable carrier according to methods known in the art.
- suitable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, and xylitol, starches such as corn starch, potato starch, and wheat starch, cellulose, methylcellulose, ethylcellulose, sodium carboxymethylcellulose, Cellulose such as hydroxypropylmethylcellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable oil, ethanol, grease. Serol, etc. can be mentioned.
- sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, and xylitol
- starches such as corn starch, potato starch, and wheat starch
- cellulose methylcellulose, ethylcellulose, sodium carboxymethylcellulose
- Cellulose such as hydroxypropylmethylcellulose, poly
- Suitable binders include starch, magnesium aluminum silicate, starch ferrite, gelatin, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, glucose, corn sweetener, sodium alginate, polyethylene glycol, and wax, and as a lubricant, oleic acid.
- examples include sodium, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, silica, talcum, stearic acid, its magnesium and calcium salts, and polydethylene glycol.
- Disintegrants include starch and methyl cellulose.
- diluents include lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, etc.
- the pharmaceutical composition of the present invention when prepared as a parenteral formulation, it can be formulated in the form of injections, transdermal administration, nasal inhalation, and suppositories along with a suitable carrier according to methods known in the art.
- a suitable carrier When formulated as an injection, an aqueous isotonic solution or suspension can be used as a suitable carrier.
- an isotonic solution such as PBS (phosphate buffered saline) containing triethanolamine, sterile water for injection, or 5% dextrose can be used.
- PBS phosphate buffered saline
- sterile water for injection sterile water for injection
- 5% dextrose can be used.
- transdermal administration it can be formulated in the form of ointments, creams, lotions, gels, external solutions, paste preparations, linear preparations, and aerol preparations.
- nasal inhalation it can be formulated in the form of an aerosol spray using suitable propellants such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, and carbon dioxide.
- propellants such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, and carbon dioxide.
- the carrier is Wethepsol ( witepsol), Tween 61, polyethylene glycols, cocoa fat, laurel paper, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, sorbitan fatty acid esters, etc. can be used.
- the preferred dosage of the pharmaceutical composition of the present invention is in the range of 0.001 mg/kg to 10 g/kg per day, preferably 0.001 mg/kg to 1 g, depending on the patient's condition, weight, gender, age, patient's severity, and administration route. It may be in the /kg range. Administration can be done once a day or divided into several times. These dosages should not be construed as limiting the scope of the invention in any respect.
- a composition for improving intestinal function using turnip extract can be provided.
- composition of the present invention can be commercialized as food or medicine.
- Figures 1 and 2 show the results of cytotoxicity evaluation of turnip extract on LS174T cells and Caco-2 cells.
- Figure 3 shows the results of evaluating the expression level of the MUC2 mucin gene in turnip extract in LS174T cells.
- Figure 4 shows the results of evaluating the expression level of the gene ZO-1, a tight junction protein of turnip extract, in Caco-2 cells.
- Figure 5 shows the results of measuring the number of blood lymphocytes in animal experiments.
- Figure 6 shows the results of evaluating the degree of IgA production in the small intestine.
- Figure 7 shows the results of evaluating the expression level of GM-CSF in small intestine Peyer's patches.
- Figure 8 shows the results of evaluating the size and number of lymphocytic follicular compartments in small intestine Peyer's patches.
- LS174T and Caco-2 cells To measure the safety of LS174T and Caco-2 cells, 200 ⁇ L of cells at a concentration of 5 ⁇ 105 cell/mL were dispensed into 96 well plates. After stabilization in a 5% CO 2 incubator (37°C) for about 16 to 20 hours, the extract samples of the above examples were treated for 12 hours according to concentration. To measure cytotoxicity, the supernatant was removed and 100 ⁇ L of 10% EZ cytox (DoGenBio, Seoul, Korea) dissolved in SFM (Serum Free Media) was added. After 30 minutes, absorbance was measured at 450 nm. Relative cell viability (%) was expressed as a percentage of the negative control. Cell morphology was observed using an inverted microscope (CKX53, OYMPUS, Tokyo, Japan).
- MUC2 mucin gene
- the level of MUC2 mucin gene expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR).
- LS174T cells (5 ⁇ 10 5 cell/mL) were dispensed at 500 ⁇ L each into a 24 well plate and stabilized in a 5% CO 2 incubator (37°C) for about 16 to 20 hours. And the extract samples of the above examples were treated at each concentration for 12 hours.
- RNA was isolated using the Total RNA Extraction Kit (iNtRON BIOTECHNOLOGY, Daejeon, Korea).
- NC negative control
- PC propionate administration group
- L low-dose experimental group
- H high-dose experimental group
- mice were sacrificed and blood (300-500 ⁇ L/mouse) was collected from the sacrificed mice.
- blood 300-500 ⁇ L/mouse
- a drop of blood was taken before it clotted and placed on one end of a glass slide. Prepare an extra slide, place it in front of the blood drop at an angle of 30° to 45°, and gently smear the slide to create an ideal zone.
- the number of lymphocytes in the smeared blood was measured using Wright-Giemsa solution (15022; MUTO PURE CHEMICALS CO., Japan), and the results are shown in Figure 5.
- the extract samples of the examples generally increase the number of lymphocytes depending on the administered dose.
- the positive control group is the propionate administration group.
- small intestine tissue was collected from sacrificed mice and stored in a PBS/15mL conical tube.
- the small intestine tissue was cut into small pieces and vortexed vigorously for 5 minutes to extract fluid from the small intestine tissue. Afterwards, the supernatant was separated by centrifugation (3,000 rpm, 20 min, 4°C), and centrifugation was performed again with some of the supernatant under the same conditions.
- centrifugation 3,000 rpm, 20 min, 4°C
- centrifugation was performed again with some of the supernatant under the same conditions.
- To quantify the total protein level in the supernatant it was measured using the BCA Protein Assay kit (23225, Thermo Fisher Scientific).
- Measurement of the content of IgA, a mucosal immunoglobulin, in small intestinal fluid was performed by ELISA using an ELISA kit (BD bioscience, Vancouver, Canada) according to the manufacturer's instructions.
- the results are shown in Figure 6.
- the results in Figure 6 show that the production of IgA increases depending on the administered dose of the example extract sample.
- the positive control group (PC) is the propionate administration group.
- the level of GM-CSF expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR).
- primer sequence gene Genebank number forward primer reverse primer GM-CSF NM_009969.4 5'-AAGGTCCTGAGGAGGATGTG-3' 5'-GAGGTTCAGGGCTTCTTTGA-3' GAPDH NM_001411843.1 5'-ATGGTGAAGGTCGGTGTGGAAC-3' 5'-TTGATGTGTAGTGGGGTCTCGC-3'
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Abstract
La présente invention concerne une composition pour améliorer la fonction intestinale en utilisant un extrait de navet, la composition ayant pour activité de : favoriser l'expression de MUC2, qui est une protéine mucine majeure de la couche muqueuse intestinale (intestin grêle et/ou gros intestin), dans des cellules LS174T, qui sont des lignées cellulaires de cancer du côlon, sans présenter de cytotoxicité particulière ; favoriser l'expression de ZO-1, qui est une protéine majeure des jonctions serrées intestinales, dans des cellules Caco2, qui sont des lignées cellulaires de cancer du côlon ; augmenter le nombre de lymphocytes dans le sang dans des expérimentations animales ; favoriser la production d'IgA dans l'intestin grêle ; augmenter la production de facteur de stimulation de colonies de granulocytes-macrophages (GM-CSF) de plaques de Peyer ; et augmenter la taille et le nombre de compartiments de follicules lymphocytaires dans les plaques de Peyer.
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Citations (3)
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KR20100077114A (ko) * | 2008-12-27 | 2010-07-07 | 강화군 | 순무 추출물로부터 분리된 4―메톡시인돌―3―아세토니트릴을 유효성분으로 함유하는 염증성 질환의 예방 및 치료용 조성물 |
KR20180013267A (ko) * | 2016-07-29 | 2018-02-07 | 농업회사법인 패시브바이오팜주식회사 | 강화 순무를 이용한 변비 및 복부비만 개선용 식품 조성물 |
KR20220036636A (ko) * | 2020-09-16 | 2022-03-23 | 박건영 | 암 예방 효능을 갖는 백김치조성물, 순무김치조성물, 순무백김치조성물, 순무물김치조성물, 순무백김치 및 순무물김치 |
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2023
- 2023-12-06 WO PCT/KR2023/019990 patent/WO2024123075A1/fr unknown
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KR20100077114A (ko) * | 2008-12-27 | 2010-07-07 | 강화군 | 순무 추출물로부터 분리된 4―메톡시인돌―3―아세토니트릴을 유효성분으로 함유하는 염증성 질환의 예방 및 치료용 조성물 |
KR20180013267A (ko) * | 2016-07-29 | 2018-02-07 | 농업회사법인 패시브바이오팜주식회사 | 강화 순무를 이용한 변비 및 복부비만 개선용 식품 조성물 |
KR20220036636A (ko) * | 2020-09-16 | 2022-03-23 | 박건영 | 암 예방 효능을 갖는 백김치조성물, 순무김치조성물, 순무백김치조성물, 순무물김치조성물, 순무백김치 및 순무물김치 |
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LIU LIN, LIU CHANG, HUA HANYI, ZHAO WENJIN, ZHU HONGKANG, CHENG YULIANG, GUO YAHUI, QIAN HE: "Effect of polysaccharides from Tibetan turnip ( Brassica rapa L.) on the gut microbiome after in vitro fermentation and in vivo metabolism", FOOD & FUNCTION, R S C PUBLICATIONS, GB, vol. 13, no. 5, 7 March 2022 (2022-03-07), GB , pages 3063 - 3076, XP093178150, ISSN: 2042-6496, DOI: 10.1039/D1FO03821D * |
TANAKA SACHI, YAMAMOTO KANA, YAMADA KAZUKI, FURUYA KANON, UYENO YUTAKA: "Relationship of enhanced butyrate production by colonic butyrate-producing bacteria to immunomodulatory effects in normal mice fed an insoluble fraction of Brassica rapa L", APPLIED AND ENVIRONMENTAL MICROBIOLOGY, AMERICAN SOCIETY FOR MICROBIOLOGY, US, vol. 82, no. 9, 1 May 2016 (2016-05-01), US , pages 2693 - 2699, XP055798259, ISSN: 0099-2240, DOI: 10.1128/AEM.03343-15 * |
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