JP2019508363A - 細菌株を含む組成物 - Google Patents
細菌株を含む組成物 Download PDFInfo
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- JP2019508363A JP2019508363A JP2018508717A JP2018508717A JP2019508363A JP 2019508363 A JP2019508363 A JP 2019508363A JP 2018508717 A JP2018508717 A JP 2018508717A JP 2018508717 A JP2018508717 A JP 2018508717A JP 2019508363 A JP2019508363 A JP 2019508363A
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Abstract
【選択図】なし
Description
本発明の組成物は、Blautia属の細菌株を含む。実施例は、この属の細菌が、微生物叢多様性を増加させる及び/または微生物叢の安定性を誘導するのに有用であることを実証している。好ましい細菌株は、Blautia hydrogenotrophica、Blautia stercoris及びBlautia wexlerae種のものである。最も好ましくは、Blautia hydrogenotrophica、特に、受託番号DSM 10507/14294で寄託されている細菌である。
ある特定の実施形態において、本発明の組成物は、微生物叢多様性を増加させる及び/または微生物叢の安定性を誘導する際の使用のためのものである。微生物叢の多様性の低減及び/または微生物叢の安定性の低減は、多くの病的疾患及び障害に関連しており、実施例は、本発明の組成物が、微生物叢多様性を増加させる及び/または微生物叢の安定性を誘導するのに有効であり得ることを実証している。したがって、本発明の組成物を使用して治療または予防される疾患または障害は、好ましくは、健常な対象の微生物叢多様性と比較して低減した微生物叢多様性レベルに関連する疾患もしくは障害及び/または微生物叢の安定性の低減に関連する疾患もしくは障害である。このように、いくつかの実施形態において、疾患または障害は、健常な対象の微生物叢多様性と比較して低減した微生物叢多様性のレベルに関連していてよく、また、微生物叢の安定性の低減にも関連していてよい。
好ましくは、本発明の組成物は、本発明の細菌株による腸への送達及び/または腸への部分もしくは全体定着を可能にするために胃腸管に投与されるべきである。概して、本発明の組成物は、経口で投与されるが、これらは、経直腸的に、鼻腔内に、または頬側もしくは舌下経路を介して投与されてよい。
概して、本発明の組成物は、細菌を含む。本発明の好ましい実施形態において、組成物は、凍結乾燥形態で調合される。例えば、本発明の組成物は、本発明の細菌株を含む顆粒またはゼラチンカプセル、例えば、硬質ゼラチンカプセルを含んでいてよい。
本発明における使用のための細菌株は、例えば、参照文献[38〜40]に詳述されている標準の微生物学的技術を使用して培養され得る。
本発明者らは、本発明の細菌株が、健常な対象の微生物叢多様性と比較して(もしくは健常な対象の集団の微生物叢多様性と比較して)微生物叢多様性のレベルが低減していることに関連する疾患または障害及び/あるいは健常な対象と比較して(もしくは健常な対象の集団と比較して)微生物叢の安定性が低減していることに関連する疾患または障害を治療または予防するのに有用であることを確認した。このことは、本発明の細菌株が宿主免疫系に及ぼす効果の結果である可能性がある。そのため、本発明の組成物は、ワクチン組成物として投与されるとき、かかる疾患または障害を予防するのにも有用であり得る。ある特定のかかる実施形態において、本発明の細菌株は、生存可能である。ある特定のかかる実施形態において、本発明の細菌株は、腸に部分的または全体的に定着することが可能である。ある特定のかかる実施形態において、本発明の細菌株は、生存可能であり、腸に部分的または全体的に定着することが可能である。他のある特定のかかる実施形態において、本発明の細菌株は、殺傷されていても、不活性化されていても、弱毒化されていてもよい。ある特定のかかる実施形態において、組成物は、ワクチンアジュバントを含んでいてよい。ある特定の実施形態において、組成物は、注射を介して、例えば皮下注射を介しての投与用である。
本発明の実施は、別途示さない限り、当業者の範囲内の、化学、生化学、分子生物、免疫学及び薬理学の従来の方法を用いる。かかる技術は、文献において完全に説明されている。例えば、参照文献[41]及び[42〜48]などを参照されたい。
実施例1−Blautia hydrogenotrophica治療後の患者の微生物叢の変化
概要
患者微生物叢の多様性及び安定性に対するBlautia hydrogenotrophicaの効果を健常及びIBS患者において試験した。
研究デザイン
Blautia hydrogenotrophica(受託番号DSM10507及び受託番号DSM14294でも寄託されている株「Blautix」)を、IBSを有するヒト患者または健常なヒト患者に投与する第一相臨床試験を行った。患者にBlautixを投与期間(1〜16日目)に投与し、ウオッシュアウト期間が19〜23日目であった。糞便サンプルを、ベースラインの、治療前の1日目(D1);治療の最後の16日目(D−16);及び2〜4週(ウオッシュアウト)の後治療である研究の最後(EOS)において、プラセボまたはBlautix治療したIBS及び健常な対象から収集した。
Qiagen DNeasy Blood & Tissue Kitを製造業者の指示に従って使用し、ベースラインの、治療前の1日目(D1);治療の最後の16日目(D−16);及び2〜4週(ウオッシュアウト)の後治療である研究の最後(EOS)においてプラセボまたはBlautix治療したIBS及び健常な対象からの0.2gの凍結糞便サンプルから微生物DNAを抽出した。
未加工の配列データを、フラッシュ法を使用してマージトリミングした。これは、質の低い読み取り値をフィルタにかけて除去することである。USEARCHパイプライン法(version 8.1.1861_i86_linux64)を使用してシングルトンを同定し、これらをOTU(Operational Taxonomic Unit)生成ステップから遮蔽した。UPARSEアルゴリズムを使用して配列をOTUにクラスタリングした。増幅ステップにおいて生じたキメラ配列を、Chimeraslayerの参照文献データベース(ダウンロード:2016年9月9日)によるUCHIMEキメラ除去アルゴリズムを使用して除去した。次いで、USEARCHグローバル配列アルゴリズムを使用して、残存OTU配列へのシングルトンを含めた全ての読み取り値をマッピングした。インハウススクリプトを使用して、次いで、USEARCHグローバル配列アルゴリズムによって分類されているように配列をOTUにグループ化した。個体配列をOTUにグループ化して、微生物叢組成情報を得た(個体数及び多様度)。
Bray−Curtis非類似度マトリクスを、R3.3.1におけるVeganライブラリを使用して各サンプル対合について生成した。データセットを、Bray−Curtis非類似度マトリクスによる主座標分析を使用して視覚化した。
全ての時点からのサンプルを、両方の群(Blautix治療群及びプラセボ群の両方を含めた71のIBS患者及び67の健常な対照)についてプールした。分析を、完全な微生物叢データセットにおいて生成した距離測度を使用して実施した。図1は、IBS対象の微生物叢が健常な対象のものと有意に異なることを報告している。
BTBRマウスモデル
BTBRマウスモデルは、頑強な自閉症様表現型を示す同系交配の遺伝子組み換えマウスを使用する。社会的行動の欠如、反復行動の増加、及び不安に関係する行動の増加がこの株において報告されている[51]。この頑強な行動的表現型に起因して、BTBRマウスは、自閉症関係行動の治療のための新規の治療剤の効能を評価するのに理想的な動物モデルである。生存生物学的製剤によるかかる症状の軽減もまた、他の精神疾患または神経疾患の治療における生物学的製剤の効能を示し得る。
雄性BTBRマウスを室内で飼育した。該動物を、12時間暗サイクル(7:00〜19:00時に点灯)で、温度及び湿度が制御された部屋に入れた。全ての実験を、Animal Experimentation Ethics Committee of University College Corkによって承認された、欧州指針2010/63/EEC、2012年のS.I.No543の要件に従って行った。
受託番号DSM10507で、また、受託番号DSM14294でも寄託されたBlautia hydrogenotrophica細菌。
マウスが8週齢であったときに開始したBlautia hydrogenotrophicaによる投薬。これらのマウスを経口胃管栄養法によって3週間、毎日1回治療した。
経口投与用ビヒクルはPBSである。毎日の経口投与を経口胃管栄養法によって行う。
新たな糞便サンプルをBlautia hydrogenotrophicaの投与の前後に個体マウスから収集した。少なくとも20mgの新たな糞便を遠心分離管に置き、直後に氷上に置き、次いで−80℃で保存した。
時点(14日目、32日目)間の微生物叢に対するBlautix治療の効果を図8に示す。微生物叢プロファイルにおける有意な時間変動が治療前(14日目)及び治療後(32日目)の研究時点間で観察された(p値=0.001)。
動物にBlautixを投与した自閉症のマウスモデルにおいて、細菌多様性の実質的な正味の増加を含めた、微生物叢における有意な変動が観察された。
まとめ
Blautia hydrogenotrophicaの保護効果を脳虚血のマウスモデルにおいて試験した。この最後に、3つの群の5〜17のマウスを試験した。正常に行動する動物のみを研究に含めた。第1投薬日は−14日目であった。1つの群には、凍結乾燥した細菌を第1投薬日から最終まで毎日与えた。対照群にはビヒクルまたはlyobufferのいずれかを与えた。
受託番号DSM10507で、また、受託番号DSM14294でも寄託されたBlautia hydrogenotrophica細菌。
−14〜14日目:1日用量のPBS対照(lyobuffer)、凍結乾燥した粉末対照(ビヒクル)または凍結乾燥した細菌(Blautix)。
Blautixの投与前−14日目(p値=0.177)において、Blautix治療、ビヒクル及びLyobuffer群間の微生物叢プロファイルに有意な差は検出されなかった(図9Aを参照されたい)。しかし、14日目では異なる治療群で微生物叢プロファイルにおいて有意差が観察され(図9Bを参照されたい)、0.011のp値が観察された。本発明者らは、Blautix治療群の微生物叢の時間変動をさらに評価したところ、有意差(図9Cを参照されたい)が見出され、0.002のp値が観察された。
Blautixは、lyobufferまたはビヒクル対照と比較したとき、脳卒中のマウスモデルにおける研究の期間にわたって微生物叢多様性の有意な増加をもたらした。
実験的自己免疫性脳脊髄炎(EAE)は、ヒト疾患MSの多くの態様を映し出しているCNS炎症のマウスモデルであり、EAEは、ヒトMSについて最も一般的に使用されている実験モデルである。EAEは、CNS特異的自己免疫障害[52]及び急性散在性脳脊髄炎を含めた他の特異的状態用のモデルとしても、より一般に使用されている。EAEは、CNS、特にMSの多くの自己免疫及び炎症障害の基礎となるメカニズムに密に対応する免疫及び炎症反応を引き起こすミエリンペプチド及びアジュバントによる免疫付与を使用して誘導される。EAEにおいて効能を示す多くの治療もまた、ヒト患者におけるMSの治療において効能を示している[52]。最も重要なことには、EAEは、炎症、脱髄、軸索消失及びグリオーシスを含めた、MSの重要な特徴を再現する。脱髄の効果は、EAEにおいて脊椎に主に制限されており、脳幹及び小脳の変化が少ない。EAEにおいて、CD4+T細胞は、CNSにおいて見出されている優位な細胞集団である。
Blautia hydrogenotrophica(受託番号DSM10507で、また、受託番号DSM14294でも寄託された「Blautix」株)を凍結乾燥粉末として使用し、必要に応じて再構成した。
0日目:MOG/CFA、1回、SC
0日目:PTx、1回、IP
2日目:PTx、1回、IP
7日目:MOG/CFA、1回、SC
治療を調製の15分間以内に行った。Blautixを2×108;100μl/マウスの用量で投与した。
MSモデルについての時点(−14日目、−1日目、34日目)間の微生物叢に対するBlautix治療の効果を図10に示す。微生物叢プロファイルにおける有意な時間変動を研究時点について観察した(p値=0.001)。
Blautixは、微生物叢多様性の有意な増加をもたらし、多発性硬化症について、動物モデルにおける治療の際に有意な時間変動を結果として生じた。
配列番号1(Blautia stercoris株GAM6−1 16SリボソームRNA遺伝子、部分配列−HM626177)
1 tgcaagtcga gcgaagcgct tacgacagaa ccttcggggg aagatgtaag ggactgagcg
61 gcggacgggt gagtaacgcg tgggtaacct gcctcataca gggggataac agttggaaac
121 ggctgctaat accgcataag cgcacggtat cgcatgatac agtgtgaaaa actccggtgg
181 tatgagatgg acccgcgtct gattagctag ttggaggggt aacggcccac caaggcgacg
241 atcagtagcc ggcctgagag ggtgaacggc cacattggga ctgagacacg gcccagactc
301 ctacgggagg cagcagtggg gaatattgca caatggggga aaccctgatg cagcgacgcc
361 gcgtgaagga agaagtatct cggtatgtaa acttctatca gcagggaaga aaatgacggt
421 acctgactaa gaagccccgg ctaactacgt gccagcagcc gcggtaatac gtagggggca
481 agcgttatcc ggatttactg ggtgtaaagg gagcgtagac ggaagagcaa gtctgatgtg
541 aaaggctggg gcttaacccc aggactgcat tggaaactgt ttttcttgag tgccggagag
601 gtaagcggaa ttcctagtgt agcggtgaaa tgcgtagata ttaggaggaa caccagtggc
661 gaaggcggct tactggacgg taactgacgt tgaggctcga aagcgtgggg agcaaacagg
721 attagatacc ctggtagtcc acgccgtaaa cgatgaatac taggtgttgg ggagcaaagc
781 tcttcggtgc cgcagcaaac gcaataagta ttccacctgg ggagtacgtt cgcaagaatg
841 aaactcaaag gaattgacgg ggacccgcac aagcggtgga gcatgtggtt taattcgaag
901 caacgcgaag aaccttacca agtcttgaca tcgatctgac cggttcgtaa tggaaccttt
961 ccttcgggac agagaagaca ggtggtgcat ggttgtcgtc agctcgtgtc gtgagatgtt
1021 gggttaagtc ccgcaacgag cgcaacccct atcctcagta gccagcaggt gaagctgggc
1081 actctgtgga gactgccagg gataacctgg aggaaggcgg ggacgacgtc aaatcatcat
1141 gccccttatg atttgggcta cacacgtgct acaatggcgt aaacaaaggg aagcgagccc
1201 gcgaggggga gcaaatccca aaaataacgt cccagttcgg actgcagtct gcaactcgac
1261 tgcacgaagc tggaatcgct agtaatcgcg aatcagaatg tcgcggtgaa tacgttcccg
1321 ggtcttgtac acaccgcccg tcacaccatg ggagtcagta acgcccgaag tc
1 caagtcgaac gggaattant ttattgaaac ttcggtcgat ttaatttaat tctagtggcg
61 gacgggtgag taacgcgtgg gtaacctgcc ttatacaggg ggataacagt cagaaatggc
121 tgctaatacc gcataagcgc acagagctgc atggctcagt gtgaaaaact ccggtggtat
181 aagatggacc cgcgttggat tagcttgttg gtggggtaac ggcccaccaa ggcgacgatc
241 catagccggc ctgagagggt gaacggccac attgggactg agacacggcc cagactccta
301 cgggaggcag cagtggggaa tattgcacaa tgggggaaac cctgatgcag cgacgccgcg
361 tgaaggaaga agtatctcgg tatgtaaact tctatcagca gggaagatag tgacggtacc
421 tgactaagaa gccccggcta actacgtgcc agcagccgcg gtaatacgta gggggcaagc
481 gttatccgga tttactgggt gtaaagggag cgtagacggt gtggcaagtc tgatgtgaaa
541 ggcatgggct caacctgtgg actgcattgg aaactgtcat acttgagtgc cggaggggta
601 agcggaattc ctagtgtagc ggtgaaatgc gtagatatta ggaggaacac cagtggcgaa
661 ggcggcttac tggacggtaa ctgacgttga ggctcgaaag cgtggggagc aaacaggatt
721 agataccctg gtagtccacg ccgtaaacga tgaataacta ggtgtcgggt ggcaaagcca
781 ttcggtgccg tcgcaaacgc agtaagtatt ccacctgggg agtacgttcg caagaatgaa
841 actcaaagga attgacgggg acccgcacaa gcggtggagc atgtggttta attcgaagca
901 acgcgaagaa ccttaccaag tcttgacatc cgcctgaccg atccttaacc ggatctttcc
961 ttcgggacag gcgagacagg tggtgcatgg ttgtcgtcag ctcgtgtcgt gagatgttgg
1021 gttaagtccc gcaacgagcg caacccctat cctcagtagc cagcatttaa ggtgggcact
1081 ctggggagac tgccagggat aacctggagg aaggcgggga tgacgtcaaa tcatcatgcc
1141 ccttatgatt tgggctacac acgtgctaca atggcgtaaa caaagggaag cgagattgtg
1201 agatggagca aatcccaaaa ataacgtccc agttcggact gtagtctgca acccgactac
1261 acgaagctgg aatcgctagt aatcgcggat cagaatgccg cggtgaatac gttcccgggt
1321 cttgtacaca ccgcccgtca caccatggga gtcagtaacg cccgaagtca gtgacctaac
1381 tgcaaagaag gagctgccga aggcgggacc gatgactggg gtgaagtcgt aacaaggt
TTTKGTCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTCGAGCGAAGCGCTTACGACAGAACCTTCGGGGGAAGATGTAAGGGACTGAGCGGCGGACGGGTGAGTAACGCGTGGGTAACCTGCCTCATACAGGGGGATAACAGTTGGAAACGGCTGCTAATACCGCATAAGCGCACAGTATCGCATGATACAGTGTGAAAAACTCCGGTGGTATGAGATGGACCCGCGTCTGATTAGCTAGTTGGAGGGGTAACGGCCCACCAAGGCGACGATCAGTAGCCGGCCTGAGAGGGTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATCTCGGTATGTAAACTTCTATCAGCAGGGAAGAAAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGAAGAGCAAGTCTGATGTGAAAGGCTGGGGCTTAACCCCAGGACTGCATTGGAAACTGTTTTTCTTGAGTGCCGGAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACGGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTTGGGGAGCAAAGCTCTTCGGTGCCGCAGCAAACGCAATAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTATTCGAAGCAACGCGAAGAACCTTACCAAGTCTTGACATCGATCTGACCGGTTCGTAATGGAACCTTTCCTTCGGGACAGAGAAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATCGTCAGTAGCCAGCAGGTAAAGCTGGGCACTCTGAGGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGGACGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAAGCGAGCCCGCGAGGGGGAGCAAATCCCAAAAATAACGTCCCAGTTCGGACTGCAGTCTGCAACTCGACTGCACGAAGCTGGAATCGCTAGTAATCGCGAATCAGAATGTCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTCAGTAACGCCCGAAGTCAGTGACCCAACCTTAGGGAGGGAGCTGCCGAAGGCGGGATTGATAACTGGGGTGAAGTCTAGGGGGT
TTCATTGAGACTTCGGTGGATTTAGATTCTATTTCTAGTGGCGGACGGGTGAGTAACGCGTGGGTAACCTGCCTTATACAGGGGGATAACAGTCAGAAATGGCTGCTAATACCGCATAAGCGCACAGAGCTGCATGGCTCAGTGTGAAAAACTCCGGTGGTATAAGATGGACCCGCGTTGGATTAGCTTGTTGGTGGGGTAACGGCCCACCAAGGCGACGATCCATAGCCGGCCTGAGAGGGTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATCTCGGTATGTAAACTTCTATCAGCAGGGAAGATAGTGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGTGTGGCAAGTCTGATGTGAAAGGCATGGGCTCAACCTGTGGACTGCATTGGAAACTGTCATACTTGAGTGCCGGAGGGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACGGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCNGGGGAGCATGGCTCTTCGGTGCCGTCGCAAACGCAGTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAAGTCTTGACATCCGCCTGACCGATCCTTAACCGGATCTTTCCTTCGGGACAGGCGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATCCTCAGTAGCCAGCATTTAAGGTGGGCACTCTGGGGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGGATGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAAGCGAGATCGTGAGATGGAGCAAATCCCAAAAATAACGTCCCAGTTCGGACTGTAGTCTGCAACCCGACTACACGAAGCTGGAATCGCTAGTAATCGCGGATCAGAATGCCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTCAGTAACGCCCGAAGTCAGTGACCTAACTGCAAAGAAGGAGCTGCCGAA
1 gatgaacgct ggcggcgtgc ttaacacatg caagtcgaac gaagcgatag agaacggaga
61 tttcggttga agttttctat tgactgagtg gcggacgggt gagtaacgcg tgggtaacct
121 gccctataca gggggataac agttagaaat gactgctaat accgcataag cgcacagctt
181 cgcatgaagc ggtgtgaaaa actgaggtgg tataggatgg acccgcgttg gattagctag
241 ttggtgaggt aacggcccac caaggcgacg atccatagcc ggcctgagag ggtgaacggc
301 cacattggga ctgagacacg gcccaaactc ctacgggagg cagcagtggg gaatattgca
361 caatggggga aaccctgatg cagcgacgcc gcgtgaagga agaagtatct cggtatgtaa
421 acttctatca gcagggaaga aagtgacggt acctgactaa gaagccccgg ctaattacgt
481 gccagcagcc gcggtaatac gtaaggggca agcgttatcc ggatttactg ggtgtaaagg
541 gagcgtagac ggtttggcaa gtctgatgtg aaaggcatgg gctcaacctg tggactgcat
601 tggaaactgt cagacttgag tgccggagag gcaagcggaa ttcctagtgt agcggtgaaa
661 tgcgtagata ttaggaggaa caccagtggc gaaggcggcc tgctggacgg taactgacgt
721 tgaggctcga aagcgtgggg agcaaacagg attagatacc ctggtagtcc acgctgtaaa
781 cgatgaatac taggtgtcgg gtggcaaagc cattcggtgc cgcagcaaac gcaataagta
841 ttcccacctg gggagtacgt tcgcaagaat gaaactcaaa ggaattgacg gggacccgca
901 caagcggtgg agcatgtggt ttaattcgaa gcaacgcgaa gaaccttacc aaatcttgac
961 atccctctga ccgggaagta atgttccctt ttcttcggaa cagaggagac aggtggtgca
1021 tggttgtcgt cagctcgtgt cgtgagatgt tgggttaagt cccgcaacga gcgcaaccct
1081 tattcttagt agccagcagg tagagctggg cactctaggg agactgccag ggataacctg
1141 gaggaaggtg gggatgacgt caaatcatca tgccccttat gatttgggct acacacgtgc
1201 tacaatggcg taaacaaagg gaagcgaagg ggtgacctgg agcaaatctc aaaaataacg
1261 tctcagttcg gattgtagtc tgcaactcga ctacatgaag ctggaatcgc tagtaatcgc
1321 gaatcagaat gtcgcggtga atacgttccc gggtcttgta cacaccgccc gtcacaccat
1381 gggagtcagt aacgcccgaa gtcagtgacc caaccnaaag gagggagctg ccgaaggtgg
1441 gactgataac tggggtga
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Claims (40)
- 対象の微生物叢多様性を増加させる及び/または微生物叢の安定性を誘導する方法における使用のための、Blautia属の細菌株を含む組成物。
- 対象において疾患または障害を治療または予防する方法における使用のための請求項1に記載の組成物であって、前記疾患または障害が、健常な対象の微生物叢多様性と比較して低減した微生物叢多様性のレベルに関連しており、前記治療または予防が、前記対象において前記微生物叢多様性を増加させることを含む、前記組成物。
- 前記対象が、健常な対象と比較して低減した微生物叢多様性を有する、請求項2に記載の組成物。
- 前記対象が、その微生物叢において99未満の異なる細菌種及び/または190未満の異なる細菌株を有する、請求項3に記載の組成物。
- 対象において疾患または障害を治療または予防する方法における使用のための請求項1に記載の組成物であって、前記疾患または障害が、健常な対象と比較して低減した微生物叢の安定性に関連しており、前記治療または予防が、前記対象において前記微生物叢の安定性を誘導することを含む、前記組成物。
- 前記対象が、健常な対象と比較して、その微生物叢の安定性が低減している、請求項2〜5のいずれかに記載の組成物。
- IBS、IBD、肥満、2型糖尿病、1または複数の感染性疾患、1または複数のアレルギー性疾患、1または複数の自己免疫疾患または1または複数の代謝疾患/障害を治療または予防する方法における使用のための、請求項1〜6のいずれかに記載の組成物。
- 前記微生物叢多様性の増加及び/または微生物叢の安定性の誘導が、非酢酸生成細菌のための、請求項1〜7のいずれかに記載の組成物。
- 前記微生物叢多様性の増加及び/または微生物叢の安定性の誘導が、酢酸生成細菌及び非酢酸生成細菌の両方のための、請求項1〜8のいずれかに記載の組成物。
- IBS、IBD、肥満、2型糖尿病、1または複数の感染性疾患、1または複数のアレルギー性疾患、1または複数の自己免疫疾患または1または複数の代謝疾患/障害を治療または予防する方法における使用のための、Blautia属の細菌株を含む組成物。
- IBSの治療または予防における使用のための、請求項7〜9のいずれかに記載の組成物。
- IBDの治療または予防における使用のための、請求項7〜9のいずれかに記載の組成物。
- 肥満の治療または予防における使用のための、請求項7〜9のいずれかに記載の組成物。
- 2型糖尿病の治療または予防における使用のための、請求項7〜9のいずれかに記載の組成物。
- 1または複数の感染性疾患、例えば、ウイルス、細菌または真菌性疾患の治療または予防における使用のための、請求項7〜9のいずれかに記載の組成物。
- 1または複数のアレルギー性疾患、例えば、ぜんそくの治療または予防における使用のための、請求項7〜9のいずれかに記載の組成物。
- 1または複数の自己免疫疾患、例えば、関節リウマチまたは多発性硬化症の治療または予防における使用のための、請求項7〜9のいずれかに記載の組成物。
- 1または複数の代謝疾患/障害、例えば、糖尿病または肥満の治療または予防における使用のための、請求項7〜9のいずれかに記載の組成物。
- 前記対象が虚弱な高齢対象である、請求項1〜18のいずれかに記載の組成物。
- 前記対象が帝王切開によって出産された乳児である、請求項1〜19のいずれかに記載の組成物。
- 前記対象の腸において、前記微生物叢多様性が増加する、及び/または前記微生物叢の安定性が誘導される、請求項1〜20のいずれかに記載の組成物。
- 前記対象の遠位腸において、前記微生物叢多様性が増加する、及び/または微生物叢の安定性が誘導される、請求項1〜21のいずれかに記載の組成物。
- 前記細菌株がBlautia hydrogenotrophicaである、請求項1〜22のいずれかに記載の組成物。
- IBSと診断された対象において微生物叢多様性を増加させる及び/または微生物叢の安定性を誘導する方法における使用のための、Blautia hydrogenotrophica種の細菌株を含む、請求項1に記載の組成物。
- 前記細菌株が、Blautia hydrogenotrophicaの細菌株の16s rRNA配列と少なくとも97%、98%、99%、99.5%または99.9%同一の16s rRNA配列を有する、請求項1〜22のいずれかに記載の組成物。
- 前記細菌株が、受託番号DSM10507で、また、受託番号DSM14294でも寄託されているBlautia hydrogenotrophica細菌である、請求項1〜24のいずれかに記載の組成物。
- 経口投与用である、請求項1〜26のいずれかに記載の組成物。
- 1または複数の薬学的に許容可能な賦形剤または担体を含む、請求項1〜27のいずれかに記載の組成物。
- 前記細菌株が、凍結乾燥されている、請求項1〜28のいずれかに記載の組成物。
- 前記細菌株が、生存可能である、請求項1〜29のいずれかに記載の組成物。
- 前記細菌株が、腸に部分的または全体的に定着することが可能である、請求項1〜30のいずれかに記載の組成物。
- Blautiaの単一株を含む、請求項1〜31のいずれかに記載の組成物。
- Blautiaを含み、かつ、任意の他の属からの細菌を含まないか、または、かかる他の細菌を僅少な量でのみ含む、請求項1〜32のいずれかに記載の組成物。
- B.hydrogenotrophicaを含み、かつ、任意の他の種からの細菌を含まないか、または、かかる他の細菌を僅少な量でのみ含む、請求項1〜33のいずれかに記載の組成物。
- Blautiaを微生物共同体の一部として含む、請求項1〜30のいずれかに記載の組成物。
- 請求項1〜35のいずれかに記載の使用のための、請求項1〜35のいずれかに記載の組成物を含む食品。
- 請求項1〜35のいずれかに記載の使用のための、請求項1〜35のいずれかに記載の組成物を含むワクチン組成物。
- 対象における前記腸内微生物叢の多様性を増加もしくは維持する、及び/または対象において前記腸内微生物叢の安定性を誘導する方法であって、Blautia属の細菌株を含む組成物をそれを必要とする対象に投与することを含む、前記方法。
- 前記BlautiaがB.hydrogenotrophicaである、請求項36に記載の方法。
- IBS、IBD、肥満、2型糖尿病、1または複数の感染性疾患、1または複数のアレルギー性疾患、1または複数の自己免疫疾患及び1または複数の代謝疾患/障害から選択される疾患または障害を治療する方法であって、対象を、腸内微生物叢の多様性のレベルが低減している及び/またはその腸内微生物叢の安定性が低減していると診断することと、次いで、前記対象に、Blautia属の細菌株を含む組成物を投与することとを含む、前記方法。
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