JP5989661B2 - 消化器の病的状態の改善に使用するためのラクトコッカスラクティス株 - Google Patents
消化器の病的状態の改善に使用するためのラクトコッカスラクティス株 Download PDFInfo
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- JP5989661B2 JP5989661B2 JP2013543895A JP2013543895A JP5989661B2 JP 5989661 B2 JP5989661 B2 JP 5989661B2 JP 2013543895 A JP2013543895 A JP 2013543895A JP 2013543895 A JP2013543895 A JP 2013543895A JP 5989661 B2 JP5989661 B2 JP 5989661B2
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
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- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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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
- C12N1/20—Bacteria; Culture media therefor
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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Description
また、胃腸感染症は、まとめて炎症性腸疾患(IBD)と呼ばれるクローン病(CD)及び潰瘍性大腸炎(UC)を含む。
IBSは、下痢又は便秘、腹痛、腹部膨満及び排泄物中への粘液の排出を特徴とする、結腸の慢性機能疾患である。
炎症及び感染症は、IBSの発生に加担すると考えられている(Ohman及びSimren, 2010)。腸内細菌科細菌は、健常被験者と比較して、IBS被験者においてより多く観察された(Siら, 2004)。しかし、この観察結果は、他者の研究(Malinenら, 2005)においては再現されず、腸内細菌科の細菌がIBSの発生病理に加担する場合には、それが唯一の因子ではないことを示唆する。加えて、IBS被験者は、健常被験者よりも多くの腸管凝集性のエシェリシア コリ(Escherichia coli) (すなわち、病原性のエシェリシア コリ株)を保有していることが示されている(Sobieszczanskaら, 2006)。
PI-IBSは、胃腸感染症の後に発症する過敏性腸症候群のサブグループである。
PI-IBSは、欧州で、特にUKで主に報告されている。にも拘わらず、2つの近年の研究(1つは中国、1つは韓国から)は、PI-IBSが、西洋において見られるものと同程度の有病率をもって、東洋諸国においても起こっていることを報告している。
IBDは、2つの腸の炎症性疾患:クローン病又は潰瘍性大腸炎のどちらでもある。
クローン病及び潰瘍性大腸炎は、遺伝的及び環境的影響(因子)、特に微生物的影響に伴う、慢性の、特発的な免疫媒介性の疾患である。クローン病は、しばしば、局所的な膿瘍及び瘢痕に伴う下痢、痙攣、及び食欲及び体重の低下に関連づけられている。また、潰瘍性大腸炎は、粘液排出及び下血、痙攣性の腹痛並びに粘膜の炎症及び潰瘍斑点を有する浮腫を伴う下痢に関連づけられている。クローン病及び潰瘍性大腸炎は、選択的には、遠位回腸及び結腸内の最も高濃度で圧倒的に嫌気性の細菌を有する領域において起こる。微生物抗原に対する血清反応は、80%のクローン病患者において存在し、抗細菌血清学的に高い力価が重篤な疾患に関連づけられている(Mowら, 2004)。
炎症性腸疾患を治療するための抗炎症性化学物質(生物製剤とも呼ばれる)の使用は持続的に増大し、今現在では、胃腸科専門医及び医師によってIBDケアに用いられている(Bosaniら, 2009を参照)。あるいは、プロバイオティクスがIBDを軽減するために用いられ、抗炎症メカニズムが作用機序であることが示唆された(Vanderpoolら, 2008)。
ラクトコッカス ラクティス(Lactococcus lactis)細菌は、チーズ又は(ヨーグルトを含む)発酵乳製品のような乳製品において共通して見られる乳酸菌である。いくつかのラクトコッカス ラクティス細菌は、サルモネラ エンテリティディス(Salmonella enteritidis)及びエシェリシア コリのような病原性腸内細菌に対する活性を有すると記載されている(Olasupoら, 2003; Ganzleら, 1999)。
- 形態:グラム陽性の微生物、主に小さなサイズの双球菌
- 下記の糖の発酵(30℃48hでAPI 50 CH strip - API MRS培地で得られた結果):リボース、ガラクトース、グルコース、マンノース、マンニトール、Nアセチルグルコサミン、アミダグリン、アルブチン、エスクリン、サリシン、セロビオース、マルトース、ラクトース、トレハロース、アミドン、βゲンチオビオース。
- 形態:グラム陽性の微生物、主に小さなサイズの双球菌
- 下記の糖の発酵(37℃72hでAPI 50 CH strip - API MRS培地で得られた結果):リボース、ガラクトース、グルコース、マンノース、マンニトール、Nアセチルグルコサミン、アミダグリン、アルブチン、エスクリン、サリシン、セロビオース、マルトース、ラクトース、メリビオース、トレハロース、アミドン、βゲンチオビオース。
前記病原性微生物は、好ましくは、エシェリシア属、サルモネラ属、リステリア属、カンピロバクター属、シゲラ属、プロテウス属(例えばP. ミラビリス(P. mirabilis))及びクレブシエラ属からなる群より選択され、好ましくはE. コリ、L. モノサイトゲネス(L. monocytogenes)及びS. エンテリティディス種からなる群より選択される。
前記消化器疾患は、特に胃又は腸の不快感;胃又は腸の感染症;下痢;便秘;IBS;PI-IBS又はIBD (すなわちクローン病及び/又は潰瘍性大腸炎)であり得る。
前記株は、細菌の全ての形態において用いることができ、死んでいてもよいし生きていてもよく、好ましくは生きている。
前記細胞フラクションは、例えば細胞壁フラクション、細胞質フラクション又は培地上清若しくはそのフラクションであり得る。
前記代謝物は、例えば、DN 030 066株又はDN 030 087株の発酵中に産生された短鎖脂肪酸、ペプチド(例えばバクテリオシン)及び/又は化合物であり得る。
- 上記に規定されたDN 030 066 (CNCM I-1631)及びDN 030 087 (CNCM I-2807)株からなる群より選択されるラクトコッカス ラクティス株、又は
- 上記に規定されたラクトコッカス ラクティス変異株、又は
- 上記に規定されたDN 030 066株又はDN 030 087株から得られた細胞フラクション又は代謝物
を含む組成物を提供する。
前記組成物は、g乾燥重量組成物当たり、105〜1013コロニー形成単位(cfu)、好ましくは少なくとも106 cfu、より好ましくは少なくとも107 cfu、更により好ましくは少なくとも108 cfu及び最も好ましくは少なくとも109 cfuの少なくとも1つの上記に規定されたL. ラクティス株又はL. ラクティス変異株を含んでいてもよい。液体組成物の場合、これは、一般的に、104〜1012コロニー形成単位(cfu)、好ましくは少なくとも105 cfu、より好ましくは少なくとも106 cfu、更により好ましくは少なくとも107 cfu及び最も好ましくは少なくとも109 cfu/mlに相当する。
また、前記組成物は、乳製品又は発酵製品、好ましくは発酵ミルク製品又は発酵ホエイ製品のような発酵乳製品であり得る。
発酵製品は、液体の形態で存在するか又は発酵した液体を乾燥させることにより得られた乾燥粉体の形態で存在し得る。
前記発酵製品は、生鮮食品であり得る。過酷な熱処理工程を経ていない生鮮食品は、細菌株が生きた形態で存在するという利点を有する。
また、前記発酵製品は、固形、かくはん型又は飲用の形態にある、発酵した大豆、穀類及び/又は果実のような発酵植物性製品であり得る。
別の実施態様において、前記組成物は、栄養補助又は栄養サプリメントである。
また、本発明の栄養組成物は、食物サプリメント及び機能性食品を含む。
また、本発明は、CNCMに番号I-2807で寄託された株であることを特徴とするラクトコッカス ラクティス株を提供する。
前記株は、病原性微生物、好ましくは上記に規定された病原性腸内細菌の成長を阻害するか及び/又は腸上皮バリアの完全性を改善することができる。
また、本発明は、ラクトコッカス ラクティスCNCM I-2807株又は医薬として使用するための前記株を含む組成物を提供する。
また、本発明は、必要のある被験者において、前記被験者に対して上記に規定されたL. ラクティス株又は組成物を投与することを含む、上記に規定された消化器疾患を治療又は予防する方法を提供する。
サルモネラ エンテリティディスB1241、リステリア属及び病原性E.コリに対する抗微生物活性をオーバーレイアッセイで測定した。3つのラクトコッカス ラクティス株をこの試験で評価した:本発明のDN 030 066株、バクテリオシン産生株 (それぞれナイシン及びラクチシン)として以前に記載された、ラクトコッカス ラクティス亜種ラクティス DSMZ 20729及びラクトコッカス ラクティス亜種クレモリス(Lactococcus lactis subsp. cremoris) DSMZ 4645(Bartoloniら, 2004及びParkら, 2003)。
腸バリアの完全性は、T84細胞単分子層の頂端側及び底側間で観測される電位差を測定することにより評価することができる。この実験モデルは、経上皮電気抵抗(TEER)と呼ばれている(Hirotaniら, 2008)。
種々の細菌株の培養上清をPBSで洗浄した。次いで、細菌(100 cfu/細胞)をT84細胞単分子層の頂端側に加えた。ビフィドバクテリウム属64株、ラクトバシラス属32株を含む96株及びラクトコッカス ラクティス2株(DN 030 0664及びDN 030 087)をこのアッセイにおいて試験した。種々の細菌のインキュベーションの4h及び6h後、TEER値を測定し、上皮バリア機能を評価した。全ての実験は、3回独立して3連で行った。t=0におけるT84細胞の値を100%に設定した。より高いTEER値を有する7株についての結果を下記の表2に示す。
Bartoloni, A. et al. (2004) J Chemother. 16: 119-121.
Baumgart, M, et al. (2007) ISME J. 1: 403-418.
Bosani, M. et al. (2009) Biologics 3: 77-97.
Camilleri, M. (2010) Aliment Pharmacol Ther. 31: 35-46.
Cooper, R. et al. (1988) Br Med J. 296: 1432-1434.
Corinaldesi, R. et al. (2009) Aliment Pharmacol Ther. 30: 245-252.
Darfeuille-Michaud, A. et al. (1998) Gastroenterology 115: 1405-1413.
Dorofeyev, A.E. et al. (2009) Dig Dis. 27: 502-510.
Ganzle, M.G. et al. (1999) International journal of food 48: 37-50.
Garrett, W.S. et al. (2007) Cell 131: 33-45.
Harris, L.J. et al. (1992) Appl Environ Microbiol. 58: 1477-1483.
Hirotani, Y. et al. (2008) Yakugaku Zasshi 128: 1363-1368.
Ibbotson, J.P. et al. (1987) Eur J Clin Microbiol. 6: 286-290.
Ji, S. et al. J Gastroenterol Hepatol. 20: 381-386.
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Link-Amster, H. et al. (1994) FEMS Immunol Med Microbiol. 10: 55-63.
Madsen, K. et al. (2001) Gastroenterology 121: 580-591.
Malinen, E. et al. (2005) Am. J. Gastroenterol. 100: 373-382.
Marshall, J.K. et al. (2010) Gut 59: 605-611.
Miyauchi, E. et al. (2009) J. Dairy Sci. 92: 2400-2408.
Mow, W.S. et al. (2004) Gastroenterology 126: 414-424.
Ohman, L. and Simren, M. (2010) Nat Rev Gastroenterol Hepatol. 7: 163-173.
Olasupo, N.A. et al. (2003) Letters in Applied Microbiology 36: 448-451.
Park, S.H. et al. (2003) Curr Microbiol. 46: 385-388.
Peterson, D.A. (2008) Cell Host Microbe 3: 417-427.
Resta-Lenert, S. and Barrett, K.E. (2006) Gastroenterology 130: 731-746.
Ryan, M.P. et al. (1996) Appl Environ Microbiol. 62: 612-619.
Sartor, R.B. (2008) Gastroenterology 134: 577-594.
Sartor, R.B. (2009) Nestle Nutr Workshop Ser Pediatr Program 64: 121-132; discussion 132-127, 251-127.
Shao, J. and Kaushal G. (2004) Int J Pharm. 286: 117-124.
Si, J.M. et al. (2004) World J Gastroenterol. 10: 1802-1805.
Sobieszczanska, B.M. et al. (2006) J. Med. Microbiol. 55: 325-330.
Spiller, R. and Garsed, K. (2009) Gastroenterology 136: 1979-1988.
Swidsinski, A. et al. (2009) J Physiol Pharmacol. Suppl 6: 61-71.
Thabane, M. et al. (2010) Am J Gastroenterol. 105: 933-939.
Tiwana, H. et al. (1998) Br J Rheumatol. 37: 525-531.
Vanderpool, C. et al. (2008) Inflamm Bowel Dis. 14: 1585-1596.
Claims (3)
- CNCMに番号I-2807で寄託された株であることを特徴とする、ラクトコッカス ラクティス株。
- 腸上皮バリアの完全性を改善するための、請求項1に記載のL. ラクティス株を含む組成物。
- 医薬として使用するための、請求項1に記載のL. ラクティス株又は請求項2に記載の組成物。
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PCT/IB2010/055913 WO2012080789A1 (en) | 2010-12-17 | 2010-12-17 | Lactococcus lactis strains for use in improving digestive condition |
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JP2016081123A Division JP2016178929A (ja) | 2016-04-14 | 2016-04-14 | 消化器の病的状態の改善に使用するためのラクトコッカス ラクティス株 |
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ES2970986T3 (es) * | 2013-03-08 | 2024-06-03 | Univ California | Nanopartículas inorgánicas funcionalizadas con polifosfato como composiciones hemostáticas y métodos de uso |
US10383921B2 (en) | 2013-08-13 | 2019-08-20 | President And Fellows Of Harvard College | Leveraging oxidative stress pathways in lactic acid bacteria to promote gut homeostasis |
WO2015023268A1 (en) * | 2013-08-13 | 2015-02-19 | President And Fellows Of Harvard College | Leveraging oxidative stress pathways in lactic acid bacteria to promote gut homeostasis |
US11135181B2 (en) | 2014-10-28 | 2021-10-05 | Medlab Ip Pty Ltd | Treatment for depression and depressive disorders |
CN104382948A (zh) * | 2014-11-21 | 2015-03-04 | 江南大学 | 乳酸乳球菌在治疗肠道疾病中的一种应用方法 |
JP6152231B1 (ja) * | 2017-01-06 | 2017-06-21 | 株式会社日本バリアフリー | 腸内フローラ改善剤 |
CN110891583B (zh) | 2017-07-18 | 2023-06-06 | 学校法人庆应义塾 | 针对Th1细胞诱导性细菌的抗菌组合物 |
EP3787668B1 (en) * | 2018-05-03 | 2023-10-25 | Crigasseni AG | Probiotic bacterial strains producing antimicrobial proteins and compositions comprising these for use in the treatment of clostridium difficile infection |
US20220152126A1 (en) * | 2019-02-01 | 2022-05-19 | Institut National De Recherche Pour L'agriculture, L'alimentation Et L'environnement | Lactococcus lactis strains for the prevention and/or the treatment of visceral pain |
CN113573780A (zh) * | 2019-03-07 | 2021-10-29 | 学校法人庆应义塾 | 针对耐药性细菌或炎症诱导性细菌的抗菌组合物 |
CA3140038A1 (en) * | 2019-05-13 | 2020-11-19 | Sami-Sabinsa Group Limited | Fructophilic lactic acid producing bacteria |
TW202106872A (zh) | 2019-07-03 | 2021-02-16 | 國立大學法人弘前大學 | 源自生長於白神山地之黃檗之新穎乳酸菌 |
BR112022002106A2 (pt) * | 2019-08-09 | 2022-04-12 | Gervais Danone Sa | Composições fermentadas e processos de preparação das mesmas |
CN116121110A (zh) * | 2022-10-28 | 2023-05-16 | 益加生物科技成都有限公司 | 一种抑菌和抗炎作用较强的乳酸乳球菌yj0801及其应用 |
CN117736943B (zh) * | 2024-02-20 | 2024-05-24 | 山东中科嘉亿生物工程有限公司 | 一种改善肠易激综合征的复合菌剂及其制备方法和用途 |
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FR2740471B1 (fr) * | 1995-10-31 | 1997-12-19 | Gervais Danone Co | Ferments lactiques, et leur utilisation pour l'obtention de produits hypocholesterolemiants |
PE20030284A1 (es) | 2001-07-26 | 2003-05-01 | Alimentary Health Ltd | Cepas de bifidobacterium |
WO2004029082A1 (ja) * | 2002-09-25 | 2004-04-08 | Fukuoka Prefectural Government | 乳酸菌が産生する抗菌性物質 |
FR2855182B1 (fr) | 2003-05-19 | 2005-08-05 | Gervais Danone Sa | Nouveaux procede et inoculum pour fermentation lactique acidifiante |
JP4589618B2 (ja) * | 2003-11-28 | 2010-12-01 | 独立行政法人農業生物資源研究所 | 免疫調節性機能を誘導する乳酸菌類とその成分 |
JP4911700B2 (ja) * | 2004-03-31 | 2012-04-04 | 株式会社明治 | 抗菌性組成物 |
AU2006296837B2 (en) | 2005-09-28 | 2012-12-13 | Nordic Rebalance A/S | Treatment of IBD and IBS using both probiotic bacteria and fermented cereal as treatment effectors |
JP5527690B2 (ja) * | 2007-11-19 | 2014-06-18 | 株式会社明治 | 免疫調節性機能誘導剤及び食品組成物 |
ES2395838T3 (es) | 2007-12-21 | 2013-02-15 | Compagnie Gervais Danone | Método para disminuir el contorno abdominal administrando una bacteria del tipo Bifidobacterium |
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US9408878B2 (en) | 2016-08-09 |
BR112013015255A2 (pt) | 2016-09-13 |
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US20130336944A1 (en) | 2013-12-19 |
CN103370073A (zh) | 2013-10-23 |
EP2651423B1 (en) | 2015-09-30 |
CN103370073B (zh) | 2017-12-05 |
EP2651423A1 (en) | 2013-10-23 |
JP2014501100A (ja) | 2014-01-20 |
WO2012080789A1 (en) | 2012-06-21 |
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RU2013132931A (ru) | 2015-01-27 |
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