JP2022523701A - 内臓痛の予防および/または処置のためのラクトコッカス・ラクティス株 - Google Patents
内臓痛の予防および/または処置のためのラクトコッカス・ラクティス株 Download PDFInfo
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Abstract
Description
1.1.細菌株、培地および培養条件:
データセットは、ラクトコッカス・ラクティス亜種ラクティスに属する4つの株から構成される。2つの株、NCDO2118およびNCDO2727は野菜から単離されたが、CNCM I-5388およびCNCM I-5386は、乳製品由来である(それぞれ生乳および乳清)。
培養上清または酵素アッセイの反応混合物中のGABA濃度を、HPLC(Agilent Technologies1200 Series、Waldbronn、Germany)によって測定した。
50mgの細菌細胞を、7時間の培養で回収した。細胞を、0.2%のKClで2回洗浄し、4.5mMのMgCl2、22%のグリセロール、および1.5mMのDTTを含有する酢酸ナトリウム緩衝液(100mM、pH4.6)に懸濁した。細胞を、超音波処理(離間した30秒および60秒の4サイクル、6.5m/秒)によって破壊し、処理中は氷上に保持した。細胞残屑を、10,000gおよび4℃で15分間の遠心分離によって除去した。
2.1.インビトロGABA産生:
NCDO2118株、CNCM I-5388株、CNCM I-5386株、およびNCDO2727株について、培養全体にわたってバイオマスおよびGABA濃度を測定した(図2)。
NCDO2118株では、高いGABA産生能と一致して高いGAD活性が得られたが、NCDO2727株では、その量が極めて低かった(表3)。GAD活性の中間レベルをCNCM I-5386株で得た一方で、非常に高い活性をCNCMI-5388株で測定した。しかしながら、7時間の中性pH条件下では、NCDO2118株、CNCM I-5388、またはCNCM I-5386のGAD活性は、バイオリアクターに蓄積したGABA産生が低かったにもかかわらず、高かったことに注目することができ、GABA産生のための酵素装置は細胞内で既に発現されているが、まだ活性ではなかったことを示唆している。
1.1.動物および外科的手順:
成体雌Wistarラット(200~225g)をJanvier Labs(Le Genest St Isle、France)から購入し、標準条件下(温度22±2℃および12時間の明/暗サイクル)でポリプロピレンケージに個別に収容した。動物には、水および食物(標準ペレット2016、Envigo RMS SARL、Gannat、France)を自由に摂取させた。すべての実験は、欧州指令2010/63/UEに従い、Local Animal Care and Use Committeeによって承認された。
雌ラットは、その環境への慣れを達成するために、結腸直腸膨張(CRD)の前の数日間、移動、逃避、または方向転換ができないポリプロピレントンネル(長さ20cmおよび直径7cm)内にいることに慣れさせた。
概日リズムの影響を最小限に抑えるために、すべてのストレスセッションを同じ時間帯(午前10時~正午12時)に行った。
強制経口投与による10日間の処置に基づいて、4つの一連の実験を、各シリーズについて、EMGを備えた7~12匹の雌ラットからなる3つの群を使用して行った。
動物実験については、データを平均±平均の標準誤差(SEM)として報告する。統計分析については、ソフトウェアGraphPad Prism 6.0(GraphPad、San Diego、CA)を使用した。一元配置ANOVA、続いてTukeyの多重比較検定を行って、異なる動物群間でデータを比較した。統計学的有意性は、P<0.05で認めた。
2.1.基礎およびストレス誘発性結腸直腸感受性に対する遊離グルタミン酸の効果
基礎条件下(すなわち、PRSの前)で、ビヒクルで処置したラットでは、漸進的な結腸直腸膨張(CRD)は、圧力依存的に腹部収縮の頻度を増加させた(図3)。
CRDに対するストレス誘発性内臓過敏に対するL.ラクティスNCDO2118およびNCDO2727の影響を図4に示す。
1.1.細菌株
NCDO2118およびNCDO2727株を使用した。
NCDO2118株において、NCBI-GenBankデータベースに受託番号CP009054で寄託されている染色体配列から、gadオペロン配列を抽出した。
この欠失により、同じ培養条件下で、変異体は野生型と同様に増殖することができた(増殖速度0.65h-1)。しかしながら、これらの条件下では、GABAは産生されず(24時間で0.29mM未満)、7時間でGAD活性は検出されなかった。
動物の調製は、実施例2に記載したものと同じである。
CRDに対するストレス誘発性内臓過敏に対するL.ラクティスNCDO2118、CNCM I-5388、およびCNCM I-5388Δgadの経時的な影響を図5および図7に示す。
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Claims (17)
- 腹部痛または内臓痛の予防および/または処置に使用するための、24時間以下の培養時間で少なくとも10mMのγ-アミノ酪酸(GABA)を産生することができるラクトコッカス・ラクティス(Lactococcus lactis)株。
- 腹部痛または内臓痛の予防および/または治療に使用するための、7時間~8時間に含まれる培養時間において、少なくとも20μモル/分ピリドカル-5’-リン酸(PLP)依存性酵素グルタミン酸デカルボキシラーゼ(GAD)mgを産生するラクトコッカス・ラクティス株。
- CNCM I-5388、CNCM I-5386、およびNCDO2118からなる群で選択されることを特徴とする、請求項1または請求項2に記載のラクトコッカス・ラクティス株。
- 遊離グルタミン酸の存在下で投与されることを特徴とする、請求項1から3のいずれか一項に記載のラクトコッカス・ラクティス株。
- 内臓痛の予防および/または処置に使用するための、請求項1から3のいずれか一項に記載のラクトコッカス・ラクティス株から得られる細胞画分。
- 内臓痛の予防および/または処置に使用するための、請求項1から3のいずれか一項に記載のラクトコッカス・ラクティス株または請求項4に記載の細胞画分を含む組成物。
- 1日当たり少なくとも106コロニー形成単位(cfu)のラクトコッカス・ラクティス株の投与を可能にする、該L.ラクティス(L.lactis)株の含有量を含むことを特徴とする、請求項6に記載のラクトコッカス・ラクティス株を含む組成物。
- 遊離グルタミン酸も含むことを特徴とする、請求項6または請求項7に記載の組成物。
- 食品であることを特徴とする、請求項6から8のいずれか一項に記載の組成物。
- 内臓痛が心理的ストレス事象および/または不安に関連することを特徴とする、請求項1から3のいずれか一項に記載のラクトコッカス・ラクティス株または請求項5に記載の細胞画分または請求項6から9のいずれか一項に記載の組成物。
- 内臓痛が口腔灼熱症候群(BMS)によるものであることを特徴とする、請求項10に記載の使用のための、請求項1から3のいずれか一項に記載のラクトコッカス・ラクティス株または請求項5に記載の細胞画分または請求項6から9のいずれか一項に記載の組成物。
- CNCM I-5388、CNCM I-5386からなる群で選択されることを特徴とする、ラクトコッカス・ラクティス株。
- 請求項12に記載のラクトコッカス・ラクティス株から得られる細胞画分。
- 請求項12に記載のラクトコッカス・ラクティス株または請求項13に記載の細胞画分を含む組成物。
- 乾燥重量グラム当たり少なくとも106cfuを含むことを特徴とする、請求項14に記載のラクトコッカス・ラクティス株を含む組成物。
- 食品であることを特徴とする、請求項14または15に記載の組成物。
- 医薬として使用するための、請求項14または15に記載の組成物。
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EP2651423B1 (en) * | 2010-12-17 | 2015-09-30 | Compagnie Gervais Danone | Lactococcus lactis strains for use in improving digestive condition |
PL2937424T3 (pl) * | 2014-04-23 | 2017-09-29 | National Yang-Ming University | Bakteria kwasu mlekowego, kompozycja ją zawierająca i ich zastosowanie |
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- 2020-01-31 KR KR1020217024028A patent/KR20210143723A/ko unknown
- 2020-01-31 CN CN202080011051.8A patent/CN113473998A/zh active Pending
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EP3917551A1 (en) | 2021-12-08 |
KR20210143723A (ko) | 2021-11-29 |
BR112021014779A2 (pt) | 2021-10-05 |
US20220152126A1 (en) | 2022-05-19 |
WO2020157297A1 (en) | 2020-08-06 |
CN113473998A (zh) | 2021-10-01 |
CA3127726A1 (en) | 2020-08-06 |
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