JP6935632B2 - 胃腸炎の処置及び予防のためのフィーカリバクテリウム・プラウスニッツィcncm i−4573株 - Google Patents
胃腸炎の処置及び予防のためのフィーカリバクテリウム・プラウスニッツィcncm i−4573株 Download PDFInfo
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- JP6935632B2 JP6935632B2 JP2018557200A JP2018557200A JP6935632B2 JP 6935632 B2 JP6935632 B2 JP 6935632B2 JP 2018557200 A JP2018557200 A JP 2018557200A JP 2018557200 A JP2018557200 A JP 2018557200A JP 6935632 B2 JP6935632 B2 JP 6935632B2
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Description
第一の態様では、本発明は、CNCMに受託番号CNCM I−4573で寄託されたフィーカリバクテリウム・プラウスニッツィ(Faecalibacterium prausnitzii)種の細菌株を含む、個体における炎症性胃腸疾患を処置及び/又は予防する為の剤に関する。
F.prausnitziiは、フィルミクテス(Firmicutes)門の主要メンバーであり、健康なヒトの大腸の細菌叢における最も豊富な常在細菌の一つである。
本発明は、生理学的に許容される媒体中に、本発明のフィーカリバクテリウム・プラウスニッツィI−4573株を少なくとも含む組成物にも関する。
I.細菌株及び培養条件
試験したF.prausnitzii株の単離菌は、N2=85%、CO2=10%及びH2=5%を満たした嫌気チャンバー内で、1mg/mlのセロビオース(Sigma−Aldrich Chemie社(スイス、ブフス))、1mg/mlのマルトース(Sigma−Aldrich社)及び0.5mg/mlのシステイン(Sigma−Aldrich社)を添加したYBHI培地(0.5%酵母エキス添加ブレインハートインフュージョン培地)(Difco社(米国デトロイト))中37℃で培養する。
・CNCM I−4573株及びCNCM I−4573株は40歳の男性から単離され、
・A2−165(DSMZ 17677)株は34歳の女性から単離されたものである(Duncan SH et al., IJSEM, 2002, 52(Pt 6):2141−2146)。
A.細胞培養
HT−29細胞株(ATCC HTB−38)(LGC−Standars社)は、10%(w/v)の熱非働化ウシ胎児血清(FBS)(GibcoBRL社(フランス、エラニー))をペニシリンG/ストレプトマイシン(5000IU/ml,5000μg/ml)(Sigma−Aldrich社)と共に添加したダルベッコ改変イーグル培地(DMEM)(Sigma−Aldrich社)中で培養される。培養物は、25cm2の組織培養フラスコ(Nunc社(デンマーク、ロスキレ)中でコンフルエントに達するまで5%(v/v)CO2含有雰囲気中37℃でインキュベートされる。
HT−29を用いた抗炎症試験は、Kechaou他(Applied and environmental microbiology 2012, 79 (5): 1491−1499)に記載された手順に従って行われる。
統計解析は、GraphPadソフトウェア(GraphPad Software社(米国カリフォルニア州ラホヤ))によって実施される。すべてのデータは平均±SEMとして表される。
得られた結果を図1に示す。
A.細胞培養
5人の健康なドナーに由来する市販のPBMC(StemCell Technologies社(フランス))を使用する。
F.prausnitzii菌との共培養アッセイ用のPBMCを調製するため、フラスコを水浴中37℃で融解し、次いで10%熱非働化FCS、1%L−グルタミン及び0.1%ペニシリン/ストレプトアビジンを添加したRPMI−1640培地(培地の成分はLonza社(スイス)から購入)を含む培地に移す。細胞の凝集を防ぐため、DNase(100μg/ml、Roche Applied Science社(フランス))を培地に加えた。
統計解析は、GraphPadソフトウェア(GraphPad Software社(米国カリフォルニア州ラホヤ))によって実施される。すべてのデータは平均±SEMとして表される。
得られた結果を図2に示す。
A.DNBS大腸炎の誘導及び菌投与
DNBS誘導大腸炎プロトコルは既報の通りである(Martin R, et al. Infiamm Bowel Dis. Mars 2014 ; 20(3):417−30)。
マウスを頸椎脱臼により屠殺し、腹腔を開く。結腸及び小腸を取り出し、縦に開き、巨視的損傷について直ちに評価する。
好中球浸潤マーカーとして用いられるミエロペルオキシダーゼ(MPO)活性は、Bradley他(J. Invest. Dermatol. 1982, 78(3):206−209)に記載された方法の変法によってアッセイする。
1cm長の遠位結腸を回収し、組織破砕装置(tissue lyser)において、プロテアーゼ阻害剤(Sigma−Aldrich)を含むTris−HCl緩衝液400μl中でホモジナイズする。
統計解析は、GraphPadソフトウェア(GraphPad Software社(米国カリフォルニア州ラホヤ))によって実施される。
1.図4の巨視的スコアは、I−4573株で処置したDNBSマウスにおいて、大腸炎のない対照マウスで得られたものと同等の、非常に良好なスコアが得られたことを示す。
Claims (13)
- CNCMに受託番号CNCM I−4573で寄託されたフィーカリバクテリウム・プラウスニッツィ(Faecalibacterium prausnitzii)種の細菌株を含む、個体における炎症性胃腸疾患を処置及び/又は予防する為の剤。
- 個体が哺乳動物である、請求項1に記載の剤。
- 個体がヒトである、請求項1又は請求項2に記載の剤。
- 炎症性胃腸疾患が炎症性腸疾患である、請求項1乃至請求項3のいずれか1項に記載の剤。
- 炎症性胃腸疾患が結腸炎症性腸疾患である、請求項1乃至請求項4のいずれか1項に記載の剤。
- 結腸炎症性腸疾患が、クローン病、潰瘍性大腸炎及び回腸嚢炎からなる群から選択される、請求項5に記載の剤。
- 結腸炎症性腸疾患が、クローン病及び潰瘍性大腸炎からなる群から選択される、請求項5又は請求項6に記載の剤。
- CNCMに受託番号CNCM I−4573で寄託されたフィーカリバクテリウム・プラウスニッツィ(Faecalibacterium prausnitzii)種の細菌株及び生理学的に許容される媒体を含む、個体における炎症性胃腸疾患を処置及び/又は予防する為の組成物。
- 経口組成物である、請求項8に記載の組成物。
- 栄養補助食品である、請求項8に記載の組成物。
- 前記組成物が、薬剤として107〜1011コロニー形成単位(cfu)に相当する1日投与量、好ましくは109cfuの1日投与量、の形態での投与に適している、請求項8乃至請求項10のいずれか1項に記載の組成物。
- 前記組成物が経口投与用のものであり、食品、飲料、医薬品、機能性食品、食品添加物、栄養補助食品及び乳製品からなる群から選択される、請求項8乃至請求項11のいずれか1項に記載の組成物。
- 前記組成物が経口投与用のものであり、栄養補助食品である、請求項12に記載の組成物。
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FR1650567A FR3046934B1 (fr) | 2016-01-25 | 2016-01-25 | Souche de faecalibacterium prausnitzii cncm i-4573 pour le traitement et la prevention d'une inflammation gastro-intestinale |
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PCT/EP2017/051306 WO2017129515A1 (fr) | 2016-01-25 | 2017-01-23 | Souche de faecalibacterium prausnitzii cncm 1-4573 pour le traitement et la prevention d'une inflammation gastro-intestinale |
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WO2017129515A1 (fr) | 2017-08-03 |
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US10918678B2 (en) | 2021-02-16 |
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AU2017211244B2 (en) | 2019-05-16 |
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