WO2012005240A1 - Bifidobacterium having activity of reducing amount of intestinal putrefacted substance - Google Patents
Bifidobacterium having activity of reducing amount of intestinal putrefacted substance Download PDFInfo
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- WO2012005240A1 WO2012005240A1 PCT/JP2011/065350 JP2011065350W WO2012005240A1 WO 2012005240 A1 WO2012005240 A1 WO 2012005240A1 JP 2011065350 W JP2011065350 W JP 2011065350W WO 2012005240 A1 WO2012005240 A1 WO 2012005240A1
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- concentration
- bifidobacteria
- reducing
- intestinal
- microorganisms
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Images
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
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- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
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- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
Definitions
- the present invention relates to a method for improving the state of enteric bacteria. More specifically, the present invention relates to selection of useful microorganisms that reduce indole compounds that cause rot odor caused by intestinal bacteria, and the selected microorganisms.
- Non-patent Document 1 An increasing number of people complain of symptoms such as repeated constipation and diarrhea, stomach up, and outgassing due to disordered eating habits, irregular lifestyles, and stress. These symptoms are thought to be due to the influence of the intestinal environment, in other words, the prevalence of spoilage bacteria in the intestinal flora.
- the intestinal microflora produces spoiled odor components such as indole and its derivatives from tryptophan under anaerobic conditions.
- Several studies have been conducted on the relationship between such intestinal flora and the production of spoilage products (Non-patent Document 1).
- Indole is also considered to be produced from tryptophan by intestinal spoilage bacteria, absorbed from the intestine, metabolized to indoxyl in the liver, and further combined with sulfuric acid to become indoxyl sulfate. In healthy humans, indoxyl sulfate is excreted in the urine, but it is considered to cause complications such as uremia in dialysis patients and the like (Non-patent Document 2).
- Patent Document 1 uses a bifidobacterum / thermophilum having an indole-reducing ability.
- Patent Document 2 describes that an extract or finely ground product of a Salacia plant is used in combination with lactic acid bacteria and / or bifidobacteria to improve the intestinal environment.
- Patent Document 3 describes that a composition containing propionic acid bacteria promotes the growth of bifidobacteria in the intestine and prevents the release of malodorous gases. It has also been reported that inulin and oligosaccharides are useful for improving the intestinal bacterial flora (Non-patent Document 3).
- the present invention has an object to effectively reduce enteric spoilage substances by effectively using highly safe and useful microorganisms.
- the above-mentioned spoilage substances are mainly produced in the large intestine, and examples of microorganisms (bacteria species) that are dominant in the large intestine include lactic acid bacteria and bifidobacteria (genus Bifidobacterium).
- This bifidobacteria has been used for food since ancient times as a microorganism that exhibits useful functions in vivo, and has a track record of eating experience. Therefore, it is a first object of the present invention to select microorganisms (strains) that can effectively reduce spoilage substances from bifidobacteria predominate in the human body (intestines).
- the present invention provides a second in vitro and in vivo system suitable as a verification or search system for the action effect of a substance or microorganism that reduces spoilage substances generated in vivo (in the intestine). Let it be an issue.
- the present inventor completed the present invention by isolating strains that effectively reduce intestinal spoilage substances from lactic acid bacteria and bifidobacteria as highly safe and useful microorganisms based on the screening method of the present invention. It was.
- the inventor of the present application uses a buffer solution to proliferate bacterial cells when screening in vitro as a verification system for the action effect of a substance or microorganism that reduces spoilage substances generated in the living body (intestine).
- the inventor of the present application is characterized in that the reaction solution is set (designed) to the amount of glucose that is the minimum energy necessary for the reduction of spoilage substances under conditions where lactic acid bacteria and bifidobacteria hardly grow.
- An in-vitro selection method and / or evaluation method for microorganisms (such as lactic acid bacteria and bifidobacteria) that reduce spoilage substances produced by intestinal bacteria was established.
- the inventor of the present application uses a mouse as a verification system for the action effect of a substance or a microorganism that reduces spoilage substances generated in vivo (in the intestine), from the serum, using a mouse.
- a mouse was studied to measure indoxyl sulfate.
- the present inventor added fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) and tryptophan (L-Tryptophan) to the diet (powder diet), raised the mouse, and indoxyl sulfate in the serum.
- a method for selecting and / or evaluating microorganisms such as lactic acid bacteria and bifidobacteria
- concentration such as lactic acid bacteria and bifidobacteria
- strains that can effectively reduce spoilage substances
- the present inventor first selects bifidos that are generally dominant in the human body (intestines) as highly safe and useful microorganisms. Focusing on the fungus, a total of 196 strains, 32 strains of Bifidobacterium ifbreve, 92 strains of Bifidobacterium longum, 72 strains of Bifidobacterium adolescenti, were screened and evaluated by in vitro, and 9 strains were preliminarily selected.
- the present invention includes medicines and foods containing Bifidobacterium as an active ingredient, which has a strong action of reducing the indole selected above and shows a reduction action of indoxyl sulfate in serum.
- Bifidobacterium breve (B. breve) of the present invention is a human-derived strain and has an excellent effect of significantly reducing indole and indoxyl sulfate in serum in a system in which the strain itself does not grow.
- B. breve which has long been edible, has high safety, and the bifidobacteria OLB6129 of the present invention can be widely applied and applied in the food and pharmaceutical fields.
- Bifidobacterium breve live bacteria
- Bifidobacterium longum live bacteria
- B. breve OLB6129 live bacteria concentration on the serum indoxyl sulfate concentration after oral administration of B. breve OLB6129 (live bacteria) to mice Number of colonies of B.Bbreve OLB6129 in feces (Fecal) and caecal contents (cecal) detected on TOS propionate agar medium
- microorganisms that are dominant in the large intestine include Lactobacillus and Bifidobacterium (Bifidobacterium spp.). Bifidobacteria have been used in food since ancient times as microorganisms that exhibit useful functions in vivo. In addition, bifidobacteria are said to have an intestinal regulating action, and are also used for intestinal preparations, etc., which also helps improve the intestinal flora, through the improvement of the intestinal environment, diarrhea suppression, prevention of rough skin, hay fever improvement, It is also said to be effective for immunity Taoism.
- the present inventor first uses a buffer solution to reproduce conditions under which microorganisms are difficult to grow, The evaluation method of the reduction effect (reduction ability) was examined. By adopting such conditions, it is possible to select excellent microorganisms under conditions closer to the intestinal environment, in which spoilage substances can be removed even if the microorganisms do not grow. For example, the components and concentration of the reaction solution can be determined under conditions in which the target microorganism hardly grows and under conditions that set the minimum energy necessary for reducing spoilage substances.
- the amount of the medium component serving as an energy source can lower the concentration of glucose, lactose, fructose, etc., compared to the normal culture conditions of the target microorganism, and remove intestinal spoilage substances.
- a degree of 0.3 to 0.7 (w / v)% can be applied.
- fructooligosaccharide (FOS) was added to the diet.
- the reduction effect of indoxyl sulfate in the solution was confirmed.
- the mouse generally used in animal experiments is a young healthy individual, the amount of spoilage substances in the living body is suppressed to a very small amount and often falls below the detection limit. Therefore, in the present invention, in an animal experiment using a mouse, tryptophan (L-Tryptophan), which is a precursor of indole in vivo, is added to the diet (powder), and the baseline of indole generated in vivo is determined. Attempts to increase showed a significant increase in the indole baseline. In other words, the concentration of indoxyl sulfate in serum, which is an index (marker) of spoilage substances, can be evaluated stably and reliably. And the reduction
- fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) and tryptophan (L-Tryptophan) are added to a diet (powder) at a predetermined concentration, and a general mouse (for animal experiments) is added. It can be reared and the concentration of indoxyl sulfate in serum can be evaluated. At this time, the concentration of the total amount of fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) is 0.5 to 20 (w / v)%, preferably 0.5 to 15 (w / v)%, more preferably , 0.5 to 10 (w / v)%.
- fructooligosaccharide (FOS) concentration is set to 0.5 (w / v)%, the viability of B. breve OLB6129 is significant as the number of viable bacteria in feces. Has been confirmed to improve.
- the concentration of tryptophan is set to 1 to 4 (w / v)%, preferably 1.5 to 3.5 (w / v)%, and more preferably 2 to 3 (w / v)%.
- microorganisms such as lactic acid bacteria and bifidobacteria
- bifidobacteria microorganisms of the genus Bifidobacterium
- microorganisms that reduce intestinal spoilage substances The inventor of the present application generally chooses microorganisms (strains) that can effectively reduce spoilage substances as microorganisms that reduce intestinal spoilage substances.
- strains The study was conducted on lactic acid bacteria and bifidobacteria, particularly bifidobacteria, which are dominant in (1).
- a bifidobacteria a total of 196 strains including 32 strains of B. breve, 92 strains of B. longum, and 72 strains of B. adolescentis were screened and evaluated in vitro. As a result, a total of 9 strains of 6 strains of B. breve and 3 strains of B. longum were selected.
- the selected nine strains were subjected to animal experiments and evaluated in vivo. As a result, a strain that exhibits the effect of reducing indole in the intestine was selected.
- the screened Bifidobacterium breve OLB6129 (B. breve OLB6129) is an independent administrative agency, National Institute of Advanced Industrial Science and Technology, Patent Biological Deposit Center (Contact: Postal Code 305-8566, Tsukuba 1-1-1, Higashi, Tsukuba, Japan Deposited on May 26, 2010 at Center Center No. 6), and this microorganism is deposited under the accession number as FERM BP-11257.
- microorganisms that reduce intestinal spoilage 4-1 Food containing microorganisms that reduce intestinal spoilage substances
- the microorganisms (such as lactic acid bacteria and bifidobacteria, preferably B. breve OLB6129) that reduce the intestinal spoilage substances of the present invention can be added to foods. That is, as the food of the present invention, any food to which microorganisms that reduce intestinal spoilage substances are added can be mentioned, and preferably fermented milk products or fermented milk drinks to which microorganisms that reduce intestinal spoilage substances are added. More preferably, a microorganism (B.
- fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) can be mentioned. It is known that GOS can be used in the same way as FOS (http://www.nyusankin.or.jp/scientific/hosono_3.html).
- the addition amount of fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) is 0.5 to 20 (w / v)%, preferably 0.5 to 15 (w / v)% as the total concentration. Preferably, it can be set to 0.5 to 10 (w / v)%.
- the food containing a microorganism (Lactic acid bacteria, bifidobacteria, etc., preferably B. breve OLB6129) that reduces intestinal spoilage substances of the present invention is a health health for preventing or improving dialysis complications for renal dialysis patients. It can be applied as food (functional food).
- the pharmaceutical product containing a microorganism that reduces the intestinal spoilage substance of the present invention is a reducing agent for intestinal spoilage substance or prevention of dialysis complications for renal dialysis patients. It can be applied as an agent or an improving agent. Furthermore, the pharmaceutical product of the present invention can be applied as a stomach tension improving agent.
- the pharmaceutical product of the present invention can be made into appropriate dosage forms such as powders, granules, tablets, capsules, and liquids.
- the pharmaceutical of the present invention may contain fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS).
- the content of fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) is 0.5 to 20 (w / v)%, preferably 0.5 to 15 (w / v)% as the total concentration. Preferably, it can be set to 0.5 to 10 (w / v)%.
- excipients include starch, lactose, sucrose, methylcellulose, carboxymethylcellulose, sodium alginate, calcium hydrogen phosphate, synthetic aluminum silicate, microcrystalline cellulose, polyvinylpyrrolidone (PVP), and hydroxypropyl starch (HPS).
- binder include starch, microcrystalline cellulose, sodium carboxymethylcellulose, polyvinyl pyrrolidone (PVP), gum arabic powder, gelatin, glucose, sucrose, and water / ethanol solutions thereof.
- disintegrant examples include starch, carboxymethyl cellulose, carboxymethyl cellulose calcium, microcrystalline cellulose, hydroxypropyl starch, and calcium phosphate.
- lubricants for example, carnauba wax, light anhydrous silicic acid, synthetic aluminum silicate, natural aluminum silicate, synthetic magnesium silicate, hardened oil, hardened vegetable oil derivative (Sterotex HM), sesame oil, white beeswax, titanium oxide , Dry aluminum hydroxide / gel stearic acid, calcium stearate, magnesium stearate, talc, calcium hydrogen phosphate, and sodium lauryl sulfate.
- the pharmaceutical product of the present invention is desirably administered orally, and bifidobacteria have established safety, so that any amount can be administered.
- the dosage can be as much as 1 billion bifidobacteria per day.
- the number can be from 500 to 500 billion, and preferably from 10 to 500 billion.
- glucose is set to 0.7 (w / v)% or less, preferably 0.6 (w / v)% or less, and more preferably 0.55 (w / v)% or less.
- glucose is set to, for example, 0.3 (w / v)% or more, preferably 0.4 (w / v)% or more, and more preferably 0.45 (w / v)% or more.
- the composition of the reaction solution was determined for the other components.
- the composition of the reaction solution should be 20 ⁇ g each of phenol, p-cresol, indole, skatole, 0.1 M Bis-Tris, 0.75 mM magnesium sulfate (MgSO 4 ), and 0.5 (w / v)% glucose.
- PH is about 6.5.
- Example 1 Selection of microorganisms capable of reducing spoilage substances "in vitro test" A total of 199 B. breve strains, 93 B. longum strains, and 72 B. adolescentis 72 strains were statically cultured, and two B. breve strains and one B. longum strain grew extremely. It was late. Therefore, these three strains were excluded from the experiment. Finally, a total of 196 strains (evaluation / selection) of 32 strains of B. breve, 92 strains of B. longum and 72 strains of B. adolescentis were selected. did.
- this supernatant was extracted twice with diethyl ether, and the extract was made up to 5 ml, and the solution was subjected to gas chromatography (GC) to indole, phenol, p-cresol, The concentration of skatole was measured (detected).
- GC gas chromatography
- GC-2014 Shiadzu
- TC-1 GL Sciences Inc.
- ID 0.25mm
- L 30mm
- dF 0.25mm
- column temperature 60 -170 °C (increased by 5 °C / min)
- 170-250 °C increased by 20 °C / min
- carrier gas nitrogen
- flow rate 71.3 ml / min
- injector temperature 240 °C
- detector temperature 250 °C
- injection volume 1 ⁇ l.
- Table 1 32 strains of B. breve
- Table 2 92 strains of B. longum
- Table 3 72 strains of B. adolescentis
- strains whose reference numbers begin with “JCM” are stored in the following storage organizations.
- Example 2 Selection of microorganisms capable of reducing spoilage substances "in vivo test (animal experiment)" Nine strains selected in Example 1 above were screened (evaluated and selected) by animal experiments (in vivo tests).
- the strain (live bacteria) to be administered to the mice was selected (screened) by an in vitro test. Specifically, 6 strains of B. breve (MEP22023004, OLB6129, MEP22023007, MEP22023012, MEP22023015, MEP22023016) and 3 strains of B. longum (MEP22023039, MEP22023061, MEP22023078) were selected. Then, an equal volume of physiological saline was used as a control group, and the administration group of a predetermined strain (live bacteria) was compared with the effect of reducing spoilage substances. The results are shown in FIG. 1 (6 strains of B. breve) and FIG. 2 (3 strains of B. longum).
- mice Effect of presence or absence of FOS administered to living body on reduction effect of spoilage substances
- SLC Balb / c mice
- Table 5 the mice were divided into 4 groups based on body weight. Suspension of B. breve OLB6129 (viable bacteria) in water and physiological saline, and suspension of B. breve OLB6129 (viable bacteria) in saline and physiological saline with FOS added in 2 weeks Orally administered in the morning.
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Abstract
Description
ヒトの生体内(腸内)で生成される腐敗物質は発ガンや老化を促進することが知られており、生体内の腐敗物質を積極的に低減できれば、ヒトの健康に寄与できると考えられる。主として大腸内で生成される腐敗物質として、フェノール、p-クレゾール、インドール、スカトール、アンモニアなどを列挙できる。これらの腐敗物質のうち特に、インドールやスカトールなどが悪臭成分であり、また、健康に悪影響を及ぼす可能性のある成分であることから、インドールやスカトールの低減が望まれている。 1. INTRODUCTION It is known that spoilage substances produced in the human body (intestines) promote carcinogenesis and aging, and if the spoilage substances in the body can be actively reduced, it can contribute to human health. It is done. Phenol, p-cresol, indole, skatole, ammonia, etc. can be listed as spoilage substances produced mainly in the large intestine. Among these spoilage substances, indole and skatole are particularly malodorous components and components that may adversely affect health, and therefore reduction of indole and skatole is desired.
2-1.腸内腐敗物質を低減させる微生物の in vitro でのスクリーニング又は予備的なスクリーニング
微生物を使用して、腸内腐敗物質(腸内で生成され、悪臭成分などを発生する物質)を腸内環境で低減させるためには、その特定の微生物が腸内で優先的に存在することが重要である。つまり、そのような微生物が備えるべき性質として、腸内環境に適応した条件への耐性が必要となる。 2. 2. Evaluation system for verification and search of action effect of microorganisms that reduce intestinal spoilage substances 2-1. In vitro screening or preliminary screening for microorganisms that reduce intestinal spoilage substances Microorganisms are used to reduce intestinal spoilage substances (substances that are produced in the gut and generate malodorous components) in the intestinal environment. In order to achieve this, it is important that the specific microorganism is preferentially present in the intestine. In other words, as a property that such microorganisms should have, resistance to conditions adapted to the intestinal environment is required.
当初には、動物実験を実施してin vivoにより、血清中のインドキシル硫酸の低減効果を十分に確認できなかった。血清中のインドキシル硫酸の低減効果は、腸内で発揮されることが期待されるが、生体内に微生物(菌体)が投与されても、腸内に到達する前に、その大部分が死滅している可能性や、腸内に到達した後に、それが安定して維持(保持)されていない可能性が考えられた。そこで、本願発明では、生体内に微生物が投与された後に、その生残性や安定性などの向上に寄与することを期待して、フラクトオリゴ糖(FOS)を食餌へ添加してみたところ、血清中のインドキシル硫酸の低減効果を確認できた。 2-2. In vivo screening for microorganisms that reduce intestinal spoilage substance Initially, animal experiments were performed and the in vivo effect of reducing indoxyl sulfate in serum could not be fully confirmed. The effect of reducing indoxyl sulfate in the serum is expected to be exerted in the intestine, but even if microorganisms (cells) are administered in the body, most of them are reached before reaching the intestine. There was a possibility that it was dead or that it was not stably maintained (retained) after reaching the intestine. Therefore, in the present invention, after adding microorganisms into the living body, in the hope of contributing to the improvement of its survival and stability, fructooligosaccharide (FOS) was added to the diet. The reduction effect of indoxyl sulfate in the solution was confirmed.
本願発明者は、腸内腐敗物質を低減させる微生物として、腐敗物質を効果的に低減できる微生物(菌株)を選抜する目的から、一般的にヒトの生体内(腸内)で優勢とされる乳酸菌やビフィズス菌、特にビフィズス菌を対象として検討した。そして、ビフィズス菌として、B. breveの32菌株、B. longumの92菌株、B. adolescentisの72菌株の合計で196菌株について、スクリーニングを実施して、in vitroで評価した。その結果として、B. breveの6菌株と、B. longumの3菌株の合計で9菌株を選抜した。 3. Microorganisms that reduce intestinal spoilage substances The inventor of the present application generally chooses microorganisms (strains) that can effectively reduce spoilage substances as microorganisms that reduce intestinal spoilage substances. The study was conducted on lactic acid bacteria and bifidobacteria, particularly bifidobacteria, which are dominant in (1). As a bifidobacteria, a total of 196 strains including 32 strains of B. breve, 92 strains of B. longum, and 72 strains of B. adolescentis were screened and evaluated in vitro. As a result, a total of 9 strains of 6 strains of B. breve and 3 strains of B. longum were selected.
4-1.腸内腐敗物質を低減させる微生物を含有する食品
本願発明の腸内腐敗物質を低減させる微生物(乳酸菌やビフィズス菌など、好ましくは、B. breve OLB6129)は、食品に添加することができる。つまり、本願発明の食品として、腸内腐敗物質を低減させる微生物を添加した任意の食品を挙げることができ、好適には、腸内腐敗物質を低減させる微生物を添加した発酵乳製品又は発酵乳飲料を挙げることができ、さらに好適には、腸内腐敗物質を低減させる微生物(B. breve OLB6129)、並びにフラクトオリゴ糖(FOS)及び/又はガラクトオリゴ糖(GOS)を添加した発酵乳製品又は発酵乳飲料を挙げることができる。なおGOSは、FOSと同様に利用できることが知られている(http://www.nyusankin.or.jp/scientific/hosono_3.html)。また、フラクトオリゴ糖(FOS)及び/又はガラクトオリゴ糖(GOS)の添加量は、総量の濃度として、0.5~20(w/v)%、好適には、0.5~15(w/v)%、より好適には、0.5~10(w/v)%に設定することができる。 4). 4. Foods or pharmaceuticals containing microorganisms that reduce intestinal spoilage 4-1. Food containing microorganisms that reduce intestinal spoilage substances The microorganisms (such as lactic acid bacteria and bifidobacteria, preferably B. breve OLB6129) that reduce the intestinal spoilage substances of the present invention can be added to foods. That is, as the food of the present invention, any food to which microorganisms that reduce intestinal spoilage substances are added can be mentioned, and preferably fermented milk products or fermented milk drinks to which microorganisms that reduce intestinal spoilage substances are added. More preferably, a microorganism (B. breve OLB6129) that reduces intestinal spoilage substances, and a fermented milk product or fermented milk drink to which fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) is added Can be mentioned. It is known that GOS can be used in the same way as FOS (http://www.nyusankin.or.jp/scientific/hosono_3.html). The addition amount of fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) is 0.5 to 20 (w / v)%, preferably 0.5 to 15 (w / v)% as the total concentration. Preferably, it can be set to 0.5 to 10 (w / v)%.
本願発明の腸内腐敗物質を低減させる微生物(乳酸菌やビフィズス菌など、好ましくは、B. breve OLB6129)を含む医薬品は、腸内腐敗物質の低減剤、又は腎臓透析患者用の透析合併症の予防剤又は改善剤として適用することができる。さらに、本願発明の医薬品は、お腹の張りの改善剤としても適用することができる。 4-2.
The pharmaceutical product containing a microorganism (Lactic acid bacteria, bifidobacteria, etc., preferably B. breve OLB6129) that reduces the intestinal spoilage substance of the present invention is a reducing agent for intestinal spoilage substance or prevention of dialysis complications for renal dialysis patients. It can be applied as an agent or an improving agent. Furthermore, the pharmaceutical product of the present invention can be applied as a stomach tension improving agent.
まず、反応溶液の組成では、ビフィズス菌が殆ど増殖せず、インドール(腸内腐敗物質の指標)の低減効果を発揮し、その効果を明確に評価できるように、反応溶液の組成を決定した。 [Reference Example 1] Setting the conditions of the in vitro test for selecting microorganisms that have the effect of reducing spoilage substances First, in the composition of the reaction solution, Bifidobacteria hardly grow, and indole (an index of intestinal spoilage substances) The composition of the reaction solution was determined so that the reduction effect was exhibited and the effect could be clearly evaluated.
B. breveの34菌株、B. longumの93菌株、B. adolescentisの72菌株の合計で199菌株について、静置培養したところ、B. breveの2菌株、B. longumの1菌株で生育が極端に遅かった。そこで、これら3菌株を実験の対象外とし、最終的には、B. breveの32菌株、B. longumの92菌株、B. adolescentisの72菌株の合計で196菌株について、スクリーニング(評価・選抜)した。 [Example 1] Selection of microorganisms capable of reducing spoilage substances "in vitro test"
A total of 199 B. breve strains, 93 B. longum strains, and 72 B. adolescentis 72 strains were statically cultured, and two B. breve strains and one B. longum strain grew extremely. It was late. Therefore, these three strains were excluded from the experiment. Finally, a total of 196 strains (evaluation / selection) of 32 strains of B. breve, 92 strains of B. longum and 72 strains of B. adolescentis were selected. did.
上記の実施例1で選抜した9菌株を動物実験(in vivo試験)により、スクリーニング(評価・選抜)した。 [Example 2] Selection of microorganisms capable of reducing spoilage substances "in vivo test (animal experiment)"
Nine strains selected in Example 1 above were screened (evaluated and selected) by animal experiments (in vivo tests).
[実験手順]
Balb/cマウス(SLC, ♀, 6-week-old)を一週間で馴化した後に、表4のように、体重に基づいて 4群に分け、それぞれの群について、生理食塩水と生理食塩水の B. breve OLB6129(生菌)の懸濁液を、2週間で連続して午前中に経口投与した。馴化期間には全群に飼料(粉末CRF-1/FOS(和光純薬工業(株)):10(w/v)%、L-Tryptophan:2.5(w/v)%)を自由摂取させた。
After acclimatizing Balb / c mice (SLC, ♀, 6-week-old) in one week, as shown in Table 4, divided into 4 groups based on body weight. For each group, saline and saline A suspension of B. breve OLB6129 (viable bacteria) was orally administered in the morning for 2 consecutive weeks. During the habituation period, all groups were allowed to freely feed (powder CRF-1 / FOS (Wako Pure Chemical Industries, Ltd.): 10 (w / v)%, L-Tryptophan: 2.5 (w / v)%) .
B. breve OLB6129の投与期間の終了時に、血清中インドキシル硫酸の濃度を確認したところ、インドキシル硫酸の濃度の低減効果について、2 x 108 cfu/body/dayの投与群(III)と、2 x 109 cfu/body/dayの投与群(IV)では、生理食塩水の投与群(コントロール)(I)と比べて有意差があったが、2 x 107 cfu/body/dayの投与群(II)cfu/bodyでは、生理食塩水の投与群(コントロール)(I)と比べて有意差はなかった(図3)。 [Experimental result]
At the end of the administration period of B. breve OLB6129, it was confirmed the concentration of serum indoxyl sulfuric acid, about the effect of reducing the concentration of indoxyl sulfuric acid, and 2 x 10 8 cfu / body / day dose group (III), The 2 x 10 9 cfu / body / day administration group (IV) was significantly different from the saline administration group (control) (I), but 2 x 10 7 cfu / body / day administration There was no significant difference in the group (II) cfu / body compared to the physiological saline administration group (control) (I) (FIG. 3).
[実験手順]
Balb/cマウス(SLC, ♀, 6-week-old)を一週間で馴化した後に、表5のように、体重に基づいて 4群に分け、それぞれの群について、FOSを無添加の生理食塩水と生理食塩水の B. breve OLB6129(生菌)の懸濁液、FOSを添加した生理食塩水と生理食塩水の B. breve OLB6129(生菌)の懸濁液を、2週間で連続して午前中に経口投与した。馴化期間には全群に飼料(粉末CRF-1/L-Tryptophan:2.5(w/v)%)を自由摂取させた。なお、B. breve OLB6129(生菌)の濃度は、実施例3において、腐敗物質の低減効果に関して必要性が示された最低限の用量である、2 x 108 cfu/body/day に設定した。
After acclimatization of Balb / c mice (SLC, ♀, 6-week-old) in one week, as shown in Table 5, the mice were divided into 4 groups based on body weight. Suspension of B. breve OLB6129 (viable bacteria) in water and physiological saline, and suspension of B. breve OLB6129 (viable bacteria) in saline and physiological saline with FOS added in 2 weeks Orally administered in the morning. During the habituation period, all groups were allowed to freely ingest feed (powder CRF-1 / L-Tryptophan: 2.5 (w / v)%). The concentration of B. breve OLB6129 (viable bacteria) was set to 2 × 10 8 cfu / body / day, which is the minimum dose indicated in Example 3 regarding the need to reduce spoilage substances. .
FOSの投与期間の終了時に、血清中インドキシル硫酸の濃度を確認したところ、B. breve OLB6129のみの投与群では、インドキシル硫酸の濃度の低減効果は小さかった(図5)。また、インドキシル硫酸の濃度の低減効果について、FOSのみの投与群では、生理食塩水の投与群(I)と比べて有意差はなかった(図5)。一方、インドキシル硫酸の濃度の低減効果について、B. breve OLB6129とFOSの投与群では、生理食塩水の投与群(I)などと比べて有意差があった(図5)。なお、B. breve OLB6129のみの投与群と、B. breve OLB6129とFOSの投与群の2群(OLB6129 +)について、便中の B. breve OLB6129(投与菌)の菌数を測定したところ、FOSの投与群において生菌数が有意に高く観察された(図6)。 [Experimental result]
When the concentration of serum indoxyl sulfate was confirmed at the end of the FOS administration period, the effect of reducing the concentration of indoxyl sulfate was small in the administration group of B. breve OLB6129 alone (FIG. 5). In addition, regarding the effect of reducing the concentration of indoxyl sulfate, there was no significant difference between the FOS-only administration group and the physiological saline administration group (I) (FIG. 5). On the other hand, the effect of reducing the concentration of indoxyl sulfate was significantly different in the B. breve OLB6129 and FOS administration groups compared to the saline administration group (I) and the like (FIG. 5). In addition, when B. breve OLB6129 only administration group and B. breve OLB6129 and
本明細書で引用した全ての刊行物、特許および特許出願をそのまま参考として本明細書にとり入れるものとする。 FERM BP-11257
All publications, patents and patent applications cited herein are incorporated herein by reference in their entirety.
Claims (14)
- 腸内腐敗物質を低減させる、新規ビフィズス菌(Bifidobacterium breve)OLB6129(FERM BP-11257)。 New Bifidobacterium breve OLB6129 (FERM BP-11257) that reduces intestinal spoilage substances.
- 請求項1記載のビフィズス菌を有効成分とする腸内腐敗物質の低減剤。 An agent for reducing intestinal spoilage substances comprising the bifidobacteria according to claim 1 as an active ingredient.
- フラクトオリゴ糖(FOS)及び/又はガラクトオリゴ糖(GOS)を更に含む請求項2記載の腸内腐敗物質の低減剤。 The agent for reducing intestinal spoilage substance according to claim 2, further comprising fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS).
- 請求項1記載のビフィズス菌を有効成分とする血清中のインドキシル硫酸の低減剤。 An agent for reducing indoxyl sulfate in serum comprising the bifidobacteria according to claim 1 as an active ingredient.
- フラクトオリゴ糖(FOS)及び/又はガラクトオリゴ糖(GOS)を更に含む請求項4記載の血清中のインドキシル硫酸の低減剤。 The agent for reducing indoxyl sulfate in serum according to claim 4, further comprising fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS).
- 請求項1記載のビフィズス菌を有効成分とする腸内腐敗物質の低減作用を有する食品。 A food having an action of reducing intestinal spoilage substances comprising the bifidobacteria according to claim 1 as an active ingredient.
- 請求項1記載のビフィズス菌を有効成分とするインドキシル硫酸の低減作用を有する食品。 A food having an action of reducing indoxyl sulfate containing the bifidobacteria according to claim 1 as an active ingredient.
- 請求項6又は7記載の食品を発酵乳製品又は発酵乳飲料とする食品。 A food comprising the food according to claim 6 or 7 as a fermented milk product or fermented milk drink.
- フラクトオリゴ糖(FOS)及び/又はガラクトオリゴ糖(GOS)を更に含む請求項6~8のいずれか1項に記載の食品。 The food according to any one of claims 6 to 8, further comprising fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS).
- 腸内腐敗物質を低減させる微生物の in vitro のスクリーニング方法において、微生物が殆ど増殖しない条件で、かつ腐敗物質の低減に必要な最低限のエネルギーとなるグルコースの濃度を反応液へ添加することを特徴とする、前記方法。 In the screening method of microorganisms that reduce intestinal spoilage substances, the concentration of glucose that is the minimum energy necessary for reducing spoilage substances is added to the reaction solution under the condition that the microorganisms hardly grow. And said method.
- グルコースの濃度を0.3~0.7(w/v)%とする請求項10記載の方法。 The method according to claim 10, wherein the glucose concentration is 0.3 to 0.7 (w / v)%.
- 腸内腐敗物質を低減させる微生物の in vivo のスクリーニング方法であって、フラクトオリゴ糖(FOS)及び/又はガラクトオリゴ糖(GOS)、並びにトリプトファン(L-Tryptophan)を食餌へ添加し、マウスを飼育して、血清中のインドキシル硫酸の濃度を評価することを特徴とする、前記方法。 A method for screening 微生物 in vivo of microorganisms for reducing intestinal spoilage substances, comprising adding fructooligosaccharide (FOS) and / or galactooligosaccharide (GOS) and tryptophan (L-Tryptophan) to a diet, and raising a mouse The method is characterized in that the concentration of indoxyl sulfate in serum is evaluated.
- フラクトオリゴ糖(FOS)の濃度及び/又はガラクトオリゴ糖(GOS)の濃度を0.5~20(w/v)%、並びにトリプトファンの濃度を1~4(w/v)%とする請求項12記載の方法。 13. The method according to claim 12, wherein the concentration of fructooligosaccharide (FOS) and / or the concentration of galactooligosaccharide (GOS) is 0.5 to 20 (w / v)%, and the concentration of tryptophan is 1 to 4 (w / v)%. .
- 微生物を乳酸菌及び/又はビフィズス菌とする請求項10~13のいずれか1項に記載の方法。 The method according to any one of claims 10 to 13, wherein the microorganism is lactic acid bacteria and / or bifidobacteria.
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2011
- 2011-07-05 WO PCT/JP2011/065350 patent/WO2012005240A1/en active Application Filing
- 2011-07-05 CN CN201610085654.8A patent/CN105671120B/en not_active Expired - Fee Related
- 2011-07-05 CN CN201180033393.0A patent/CN102959075B/en active Active
- 2011-07-05 JP JP2012523872A patent/JP5837879B2/en active Active
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2013
- 2013-09-03 HK HK13110266.1A patent/HK1183058A1/en unknown
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2015
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2016
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Cited By (7)
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WO2018193648A1 (en) * | 2017-04-18 | 2018-10-25 | 国立大学法人東北大学 | Blood purification through alkalifying agent |
JP2018177752A (en) * | 2017-04-18 | 2018-11-15 | 国立大学法人東北大学 | Blood purification by alkalizing agent |
JPWO2018193648A1 (en) * | 2017-04-18 | 2020-02-27 | 国立大学法人東北大学 | Blood purification by alkaline agent |
JP7219898B2 (en) | 2017-04-18 | 2023-02-09 | 国立大学法人東北大学 | Blood purification with alkaline agents |
JP2020180094A (en) * | 2019-04-26 | 2020-11-05 | 森永乳業株式会社 | Composition for preventing or improving renal dysfunction, and pharmaceutical composition and food and drink composition including the composition for preventing or improving renal dysfunction |
JP7309436B2 (en) | 2019-04-26 | 2023-07-18 | 森永乳業株式会社 | A composition for preventing or improving renal dysfunction, and pharmaceutical compositions and food and drink compositions using the composition for preventing or improving renal dysfunction |
WO2021079869A1 (en) * | 2019-10-21 | 2021-04-29 | ビオフェルミン製薬株式会社 | Uremic toxin reducing agent |
Also Published As
Publication number | Publication date |
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JP5837879B2 (en) | 2015-12-24 |
JP2016028595A (en) | 2016-03-03 |
HK1183058A1 (en) | 2013-12-13 |
CN105671120B (en) | 2019-02-19 |
JPWO2012005240A1 (en) | 2013-09-02 |
CN102959075A (en) | 2013-03-06 |
HK1221748A1 (en) | 2017-06-09 |
CN102959075B (en) | 2016-03-02 |
CN105671120A (en) | 2016-06-15 |
JP6096263B2 (en) | 2017-03-15 |
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