JP2022513154A - Christensenella minutaを含むChristensenellaceae細菌およびその使用 - Google Patents
Christensenella minutaを含むChristensenellaceae細菌およびその使用 Download PDFInfo
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Abstract
Description
本出願は、2018年11月28日に出願されたスペイン特許出願第P2018/31153号の利益を主張し、これは、参照によりその全体が本明細書に組み込まれる。
本出願は、その開示の一部として、添付のテキストファイルに含有される生物学的配列表を含み、これは、参照によりその全体が本明細書に組み込まれる。
-Christensenellaceae科の別の種、特にChristensenella属および特にChristensenella minuta種の少なくとも1つの菌株、
-腸、消化管、または環境起源の少なくとも1つの乳酸菌またはビフィズス菌。乳酸菌は、これらに限定されないが、Bifidobacterium、Lactobacillus、Lactococcus、Enterococcus、Propionibacterium、Leuconostoc、Weissella、Pediococcus、またはStreptococcus属の細菌を含むリストから選択される。
-腸、消化管、または環境起源の原核生物の他の系統発生的群、属、または種の少なくとも1つの菌株、例えば、これらに限定されないが、Archaea、Firmicutes、Bacteroidetes、Proteobacteria、Actinobacteria、Verrucomicrobia、Fusobacteria、Metanobacteria、Spirochaetes、Fibrobacteres、Deferribacteres、Deinococcus、Thermus、Cianobacteria、Methanobrevibacterium、Peptostreptococcus、Ruminococcus、Coprococcus、Subdolingranulum、Dorea、Bulleidia、Anaerofustis、Gemella、Roseburia、Catenibacterium、Dialister、Anaerotruncus、Staphylococcus、Micrococcus、Propionibacterium、Enterobacteriaceae、Faecalibacterium、Bacteroides、Parabacteroides、Prevotella、Eubacterium、Akkermansia、Bacillus、Butyrivibrio、またはClostridiumなど、
-真菌または酵母の少なくとも1つの菌株、例えば、これらに限定されないが、Saccharomyces、Candida、Pichia、Debaryomyces、Torulopsis、Aspergillus、Rhizopus、Mucor、またはPenicillium属に属するものなど。
(i)病気または病的状態を阻害する、すなわち、その発症を遅らせる、
(ii)病気または病的状態を緩和する、すなわち、病気もしくは病的状態またはその症状の退行を引き起こす、
(iii)病気または病的状態を安定させる。
本特許の目的であった生物学的材料は、健康なボランティアの糞便から分離し、処理し、腸内細菌叢培地(GMM)に接種し、その組成は、以前の出版物で推奨されている培地に基づき[18]、[19]、発明者によって設計された修正を伴う。該修正は、一定のpHを維持しながら、嫌気性チャンバー内で24時間、処理された糞便を発酵させることからなる。発酵したGMM培地は、0.5%脱線維化血液を含む非常に繊細な嫌気性寒天(FAA)培地の補足として使用し、それは、プレートを嫌気性チャンバー内で37℃にて72時間インキュベートした後、糞便の連続の希釈物を接種し、コロニーを単離するために使用した。Christensenella minuta DSM32891は、成長したコロニーから単離した。
>Christensenella minuta DSM32891の16S rRNA遺伝子配列
ACTTCATGTGGGCGGGTTGCAGCCCACAATCCGAACTGGGACCGGCTTTTTGAGATTCGCTTCCCCTTACGGGTTCGCTGCCCTTTGTACCGGCCATTGTAGCACGTGTGTAGCCCAAGACATAAGGGGCATGATGATTTGACGTCGTCCCCACCTTCCTCCGAGTTGTCCCCGGCAGTCTCACTAGAGTTCCCGCCTTTACGCGCTGGCAACTAGCAATAAGGGTTGCGCTCGTTGCGGGACTTAACCCAACATCTCACGACACGAGCTGACGACAACCATGCACCACCTGTCTCTCTGCCCCGAAGGGAAACTGTATCTCTACAGTCGTCAGAGGATGTCAAGCCTTGGTAAGGTTCTTCGCGTTGCTTCGAATTAAACCACATGCTCCGCTGCTTGTGCGGGCCCCCGTCAATTCCTTTGAGTTTCAACCTTGCGATCGTACTCCCCAGGCGGGATACTTAATGCGTTTGCTTCGGCACGGAACCCTATCGGGCCCCACACCTAGTATCCATCGTTTACGGCGTGGACTACCAGGGTATCTAATCCTGTTTGCTCCCCACGCTTTCGTGCCTCAGTGTCAGTTACAGTCCAGAAAGTCGCCTTCGCCACTGGTGTTCCTCCTAATATCTACGCATTTCACCGCTACACTAGGAATTCCACTTCCCTCTCCTGTACTCAAGTCACACAGTTTCAAATGCAACCCCGGGGTTAAGCCCCGGTCTTTCACATCTGACTTACATGACCACCTACGCACCCTTTACGCCCAGTAATTCCGGACAACGCTTGCTCCCTACGTATTACCGCGGCTGCTGGCACGTAGTTAGCCGGAGCTTCCTCCTATGGTACCGTCATTTCTTTCGTCCCATAGGACAAAGGTTTACAATCCGAAGACCTTCTTCCCTCACGCGGCGTTGCTGGGTCAGGGTTTCCCCCATTGCCCAATATTCCCCACTGCTGCCTCCCGTAGGAGTCTGGACCGTGTCTCAGTTCCAGTGTGGCCGATCACCCTCTCAGGTCGGCTACCCATCGTTGACTTGGTGGGCCGTTACCTCACCAACTATCTAATGGGACGCGAGCCCATCCTGCATCGAATAAATCCTTTTACCTCAAAACCATGCGGTTTCGTGGTCTCATGCGGTATTAGCAGTCGTTTCCAACTGTTGTCCCCCGTTGCAGGGCAGGTTGCTCACGCGTTACTCACCCGTCCGCCACTCGGTATACCCACAGTTCCTCCCGAAGGATTCACAAAGGGCAACCT
急性の社会的ストレス動物モデルの開発および試料採取
青年期に達した雄のC57BL/6マウス(生後32日、Charles River、Les Oncins、フランス)をこの研究に使用した。該マウスは、温度(23oC)、相対湿度(40~50%)、および12時間の明/暗サイクルの制御された条件で維持し、11週間、標準食(D12450K、Research diet、Brogaarden、デンマーク)を与えた(最初の週は、該マウスを、動物原性感染症の可能性を防止するために用意した部屋で隔離した)。マウスを無作為に4つの実験群に分けた(n=10)。対照群(C)、ストレス群(S)、Christensenella minuta DSM32891(S+C.min)で処理した群、およびBifidobacterium breve MF217(S+B.breve)で処理した群を比較目的で使用した。S+C.min群のマウスは、10%スキムミルクに懸濁した本発明による細菌株(1x109のコロニー形成単位[CFU])の経口投与で処理し、S+B.breve群は、10%スキムミルクに懸濁したB.breve(1x109のコロニー形成単位[CFU])の投与で処理した。ビヒクルまたはプラセボ(10%スキムミルク)を対照群およびストレス群の両方に同じ方法で投与した。処理またはプラセボを10週間与えた。これらの10週間の終わりに、血液、腸、脳、糞便内容物、および糞便を含む試料を得るために、マウスを頸椎脱臼によって安楽死させた。
急性の社会的ストレスを誘発するために、居住者-侵入者パラダイムに基づく動物の社会的敗北のモデルを使用した[20]。このモデルでは、2匹の動物のうちの1匹(居住者)が自分のケージ内で縄張りを確立することを許可された。次に、研究用マウス(侵入者)、この場合はC57BL/6の雄を、居住マウスのケージに1匹ずつ導入した。これを行うために、前もって単離し、より攻撃的となるように訓練した攻撃的なCD-I菌株の成体(4週齢)の雄(Charles River、Les Oncins、フランス)を使用した(居住攻撃者として)。4日間連続で敵対的な遭遇を実施し(実験用ではないマウスを居住者のケージに10分間導入)、該マウス間の物理的接触を許可し、侵入者のマウスが高レベルのストレスに苦しんだ(高レベルのコルチコステロンの産生に反映された)。敵対的な遭遇は、該マウスが通常飼育されていた動物施設ではなく、中立的な部屋で行った。実験用マウス(侵入者)は、敵からの侵略(脅威/攻撃)を受けた後、脱出または飛行行動、および防御/服従行動も示した。動物が敗北したかどうかを定義するために採用された基準は、敗北を示す特定の姿勢の採用であった。該姿勢は、前足を引きずり、頭を上向きに傾け、耳を引っ込めた、直立した服従姿勢を特徴とする[21]。
抑うつ行為に関連する快感/無快感行動を評価するために、3%ショ糖嗜好性試験を実施した。無快感行動(快感を感じることができない)は、うつ病の最も明らかな症状の1つと考えられている[22]。異なる動物実験により、うつ病の動物は、3%未満のショ糖水を消費することが示されており、これは、無快感行動と見なされる。
マウスは、該マウスが逃げることも近くの表面にぶら下がることもできない位置で、尾の先端から約1cmに粘着テープを貼ってテーブルの端から吊るした。5分間の不動時間と同様に、脱出を試みることを目的とした行動を定量化した。不動(意欲喪失の尺度として)の持続時間を、試験が続いた5分間記録した。このテストは、マウスの抑うつ行動を評価するために一般的に使用される[21]。
この実施例は、社会的ストレスおよびうつ病の動物モデルにおけるストレスマーカーに対するC.minuta DSM32891の効果(10日)を報告する。
この例では、C.minuta菌株DSM32891のゲノム配列と、Christensenellaceae科に属する他の細菌の他の菌株との比較について説明する。
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Claims (32)
- 寄託番号DSM32891を有するChristensenella minutaの菌株。
- 請求項1に記載の菌株に由来する菌株。
- 前記菌株が、遺伝子改変された突然変異体である、請求項1または2のいずれかに記載の菌株。
- 前記菌株が、生存細胞または非生存細胞の形態である、請求項1~3のいずれかに記載の菌株。
- 請求項1~4のいずれかに記載の菌株から得られる細胞成分、代謝産物、分泌分子、またはそれらの任意の組み合わせ。
- 請求項1~4のいずれかに記載のChristensenella minutaの菌株、または請求項5に記載の細胞成分、代謝産物、分泌分子、もしくはそれらの任意の組み合わせを含む、組成物。
- 前記組成物が、少なくとも1つの生物活性成分も含む、請求項6に記載の組成物。
- 前記組成物が、請求項1~4のいずれかに記載の細菌とは異なる菌株のものである、少なくとも1つの微生物も含む、請求項6または請求項7のいずれかに記載の組成物。
- 前記微生物が、腸内細菌または乳酸菌である、請求項8に記載の組成物。
- 前記組成物が、薬学的組成物である、請求項6~9のいずれかに記載の組成物。
- 前記組成物が、少なくとも1つの薬学的に許容されるビヒクルおよび/または賦形剤も含む、請求項10に記載の組成物。
- 前記組成物が、経口、舌下、鼻、気管支、リンパ、直腸、経皮、吸入、または非経口投与に好適な形態で提示される、請求項10または請求項11に記載の組成物。
- 前記組成物が、栄養組成物である、請求項6~9のいずれかに記載の組成物。
- 前記栄養組成物が、食料品、サプリメント、栄養補給食品、プロバイオティクス、またはシンバイオティクスである、請求項13に記載の組成物。
- 前記食料品が、乳製品、植物製品、肉製品、アペリティフ、チョコレート、飲料、または離乳食から構成されるリストから選択される、請求項14に記載の組成物。
- 前記組成物が、最終組成物1グラムまたは1ミリリットルあたり104~1014のコロニー形成単位(CFU)の前記細菌の濃度を有する、請求項6~15のいずれかに記載の組成物。
- 薬剤として、または医薬品としての使用のための、請求項1~4のいずれか一項に記載のChristensenella minutaの菌株、請求項5に記載の細胞成分、代謝産物、分泌分子、もしくはそれらの任意の組み合わせ、または請求項6~16のいずれか一項に記載の組成物。
- 気分障害および/またはストレス障害および/または不安障害および/または片頭痛の予防および/または治療における使用のための、Christensenellaceae細菌、またはChristensenellaceae細菌を含む組成物。
- 気分障害および/またはストレス障害および/または不安障害および/または片頭痛の治療におけるアジュバントとしての使用のための、Christensenellaceae細菌、またはChristensenellaceae細菌を含む組成物。
- 前記気分障害が、うつ病、大うつ病、非定型うつ病、典型的またはメランコリックうつ病、心因性うつ病、カタトニック性うつ病、分娩前後のうつ病、双極性障害、季節性情動障害、気分変調、抑うつ性パーソナリティ障害、二重うつ病、特定不能の抑うつ障害、反復性短期抑うつ障害、小うつ病、精神状態の変化、および物質乱用によって、または乱用薬物などの薬物の使用によって誘発される気分障害を含むリストから選択される、請求項18または19に記載の使用のためのChristensenellaceae細菌、またはChristensenellaceae細菌を含む組成物。
- 前記ストレス障害が、反応性愛着障害、脱抑制型社会関与障害、心的外傷後ストレス障害(PTSD)、急性ストレス障害、および適応障害から選択される、請求項18または19に記載の使用のためのChristensenellaceae細菌。
- 前記不安障害が、パニック発作、パニック障害、広場恐怖症、社交恐怖症もしくは社交不安障害、強迫性障害、心的外傷後ストレス障害(ASD)、全般性不安障害、または急性ストレス障害から選択される、請求項18または19に記載の使用のためのChristensenellaceae細菌。
- 前記Christensenellaceae細菌が、Christensenella属の細菌である、請求項18~22のいずれか一項に記載の使用のためのChristensenellaceae細菌、またはChristensenellaceae細菌を含む組成物。
- 前記Christensenella細菌が、Christensenella minuta種、Christensenella timonensis種、Christensenella massiliensis種、またはそれらの組み合わせのいずれかから選択される、請求項23に記載の使用のためのChristensenellaceae細菌、またはChristensenellaceae細菌を含む組成物。
- 前記Christensenella細菌が、寄託番号DSM102344を有するChristensenella massiliensis菌株または寄託番号DSM102800を有するChristensenella timonensis菌株その組み合わせのいずれかである、請求項24に記載の使用のためのChristensenellaceae細菌、またはChristensenellaceae細菌を含む組成物。
- 前記Christensenella細菌が、請求項1~4のいずれか一項に記載の細菌から選択される、寄託番号DSM32891を有するChristensenella minutaの菌株、寄託番号DSM22607を有するChristensenella minutaの菌株、またはそれらの組み合わせのいずれかである、請求項24に記載の使用のためのChristensenellaceae細菌、またはChristensenellaceae細菌を含む組成物。
- 前記Christensenellaceae細菌が、生存細胞の形態および/または非生存細胞の形態である、請求項18~26のいずれか一項に記載の使用のためのChristensenellaceae細菌、またはChristensenellaceae細菌を含む組成物。
- 前記Christensenellaceae細菌が、寄託番号DSM32891を有するChristensenella minutaの菌株の16S rRNA配列(配列番号3)に対して少なくとも90%の同一性、少なくとも95%の同一性、少なくとも96%の同一性、少なくとも97%の同一性、少なくとも98%の同一性、少なくとも99%の同一性、または少なくとも99.5%の同一性を有する16S rRNA配列を含むか、または前記Christensenellaceae細菌が、寄託番号DSM32891を有するChristensenella minutaの菌株を含む、請求項18~27のいずれか一項に記載の使用のためのChristensenellaceae細菌、またはChristensenellaceae細菌を含む組成物。
- ヒトまたは非ヒト動物から選択される対象における使用のためである、請求項17~28のいずれか一項に記載の使用のための細菌。
- 前記非ヒト動物が、ペット、家畜動物、動物園の動物、哺乳動物、イヌ、ネコ、モルモット、フェレット、ハムスター、ブタ、ウシ、ヤギ、ヒツジ、ウマ、マウス、およびラットから選択される、請求項29に記載の使用のための細菌。
- 前記使用が、前記細菌の104~1014のコロニー形成単位(CFU)の投与を含む、請求項17~30のいずれか一項に記載の使用のための細菌。
- 食品の調製のための、請求項1~4のいずれか一項に記載の菌株、請求項5に記載の細胞成分、代謝産物、分泌分子、もしくはそれらの組み合わせのいずれか、または請求項6~16のいずれか一項に記載の組成物の使用。
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PCT/EP2019/082793 WO2020109414A1 (en) | 2018-11-28 | 2019-11-27 | Christensenellaceae bacteria including christensenella minuta and uses thereof |
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