CN1798831A - 含有与丹宁组合的植物乳杆菌菌株的组合物和新植物乳杆菌菌株 - Google Patents
含有与丹宁组合的植物乳杆菌菌株的组合物和新植物乳杆菌菌株 Download PDFInfo
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- CN1798831A CN1798831A CNA2004800153092A CN200480015309A CN1798831A CN 1798831 A CN1798831 A CN 1798831A CN A2004800153092 A CNA2004800153092 A CN A2004800153092A CN 200480015309 A CN200480015309 A CN 200480015309A CN 1798831 A CN1798831 A CN 1798831A
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Abstract
本发明涉及含与丹宁组合的一种或更多种产生丹宁酶的乳杆菌菌株的组合物,所述菌株具有粘附到人肠粘膜上的能力。新的产生丹宁酶的植物乳杆菌菌株是a。
Description
本发明涉及具有抗炎特性和对肠微生物群落的体内控制作用和体外防腐特性的组合物,所述组合物含有任选的新的、产生丹宁酶的植物乳杆菌(Lactobacillus plantarum)菌株,所述菌株具有粘附到人肠粘膜的显著能力。
发明背景
丹宁被定义为水溶性酚类产品,它们可以从水溶液中沉淀蛋白质,是天然存在的化合物。有两类丹宁,来源于没食子酸和鞣花酸的可水解丹宁,和缩合丹宁也就是原花色素,它们是黄烷醇的寡聚物和多聚物。丹宁抑制多种微生物生长并抵抗微生物攻击(Cung,K.T.,etal.,(1998),Tannins and human health:A review.CriticalReviews in Food Science and Nutrition 38:421-464)。霉菌和酵母和一些需氧细菌通常最佳地适于降解丹宁但厌氧降解也会发生,如在肠道中(Bhat,T.K.,et al.,(1998),Microbial degradationof tannins-A current perspective.Biodegradation 9:343-357)。
已知丹宁是抗营养剂,也即,它们降低身体将消化的营养物转化成新的身体物质的效率。然而,也已经有丹宁的有益健康作用的报道,例如抗癌作用、降低血压和调节免疫应答的能力。这些作用可能是由于丹宁的抗氧化特性(Chung et al.,1998)。报道有抗癌特性的有效抗氧化性丹宁是鞣花酸。具有极高抗氧化能力的另一种类型的丹宁是原花色素,例如存在于葡萄和橄榄中。因此,来源于植物的食物中存在的不同浓度的丹宁对人类健康有显著影响。不建议摄入大量丹宁因为它们可能参与癌症形成和抗营养活性,但通过影响代谢酶、免疫调节或其它功能,摄入少量正确种类的丹宁可能对健康有益(Chung etal.,1998)。
然而,正如肠道中产生的,很多丹宁的厌氧降解产物能产生具有有益健康作用的化合物(Bhat et al.,1998)。这些降解化合物是例如苯基丙酸或苯基乙酸的衍生物(Bhat et al.,1998)。当在胃肠道中被吸收时,这些化合物有抗炎作用。这些化合物与丹宁的其它降解产物一起在胃肠道中也有宽范围的抗微生物作用,而抑制不需要的细菌。
现有技术
多数乳杆菌种不能降解丹宁,但紧密相关种植物乳杆菌,戊糖乳杆菌和L.paraplantarum的菌株能具有丹宁酶活性,Osawa,R.,etal.,(2000),Isolation of tannin-degrading lactobacilli fromhumans and fermented foods,Applied and EnvironmentalMicrobiology 66:3093-3097。
通过由于存在甘露糖而被阻断的机制,一些植物乳杆菌菌株具有特异性粘附到人上皮细胞的能力,Adlerberth,I.,et al.,(1996),A mannose-specific adherence mechanism in Lactobacillusplantarum conferring binding to the human colonic cell lineHT-29.Applied and Environmental Microbiology 62:2244-2251。
发明简述
已经发现具有粘附到人肠粘膜并能产生丹宁酶的植物乳杆菌菌株,当降解丹宁时,产生抵抗胃肠(GI)道中有害细菌的化合物,这些化合物在胃肠道中被吸收时具有抗炎作用。
附图说明
附图表示通过用限制酶EcoRI切割植物乳杆菌菌株HEAL 9(泳道2)、IHEAL 19(泳道3)、299v(泳道4)和HEAL 99(泳道5)的染色体DNA而获得的分离DNA片段。高分子量DNA标记物(BRL)和DNA分子量标记物VI(Roche)被用作标准(泳道1)。
发明详述
本发明涉及含与丹宁组合的一种或多种产生丹宁酶的植物乳杆菌或紧密相关乳杆菌种的菌株的组合物,所述菌株具有粘附到人肠粘膜上的能力。所述组合物将体内产生具有抗微生物和抗炎作用的化合物,并体外产生具有防腐作用的化合物。
本发明也涉及含与丹宁和载体组合的一种或多种产生丹宁酶的乳杆菌菌株的组合物。
载体的实例是麦片糊、乳酸发酵食品、抗性淀粉。为改善细菌增殖并增加抗炎或防腐衍生物的生产,膳食纤维可以加到组合物中。膳食纤维如寡聚果糖、寡聚半乳糖、乳果糖、麦芽糖糊精、β-葡聚糖和瓜耳胶,也可用作载体。
本发明尤其涉及含产生丹宁酶的乳杆菌菌株的食物组合物,所述菌株与或多或少纯丹宁组分例如鞣花酸、类黄酮如原花色素和花色素、或木脂体类组合,或与富含丹宁的食物组分如燕麦、大麦、红高梁、松树内部皮层制造的粉和葡萄、柑桔、越橘、蓝莓、黑醋栗、蔓越橘、草莓、覆盆子和玫瑰果的果汁或提取物组合。
本发明也涉及含产生丹宁酶的植物乳杆菌菌株的药物组合物,所述菌株与或多或少纯丹宁组分一起组合,例如鞣花酸、类黄酮如原花色素或花色素、或木脂体类,或任何其它药学可接受的丹宁来源。
为了达到本发明组合物的预防或治疗作用,丹宁含量优选为约500-1000mg/天。例如对于玫瑰果粉末,这大致相当于100g,或玫瑰果浆形式4升。
丹宁是具有不同分子量的水溶性酚类产物,它们能沉淀水溶液中的蛋白质。有两类丹宁,来源于没食子酸和鞣花酸的可水解丹宁,和缩合丹宁也就是原花色素,它们是黄烷醇的寡聚物和多聚物。
所谓缩合或不可水解丹宁比可水解丹宁可更强抵抗微生物降解。丹宁通常在果实和种子中发现,如葡萄、苹果、香蕉、黑莓、蔓越橘、覆盆子、草莓、橄榄、豆类、高梁谷粒、大麦和finger millets、可可、茶和咖啡。
本发明的组合物可以是食物组合物,其中载体是食品。在药物组合物中,载体应是药学可接受的载体。所述组合物可以被给予普通消费者以改善保健措施,从而最终预防将来的疾病如胃肠来源的感染、糖尿病、炎症性肠病(IBD)、肠激惹综合征(IBS)、癌症和心血管疾病,或减轻这些举例说明的疾病。
本发明的药物组合物可以配制成例如悬液、片剂、胶囊和粉末,它们可以口服给予。所述制剂也可以作为灌肠剂给予。
本发明尤其涉及植物乳杆菌或紧密相关乳杆菌种的产生丹宁酶的菌株,所述菌株具有粘附到人肠粘膜上的能力,其特征是具有用已知方法确定的丹宁酶活性,其中排除菌株:植物乳杆菌299,DSM 6595和植物乳杆菌299v,DSM 9843,所述方法由Osawa和Walsh描述于Applied and Environmental Microbiology,Vol.59,No.4,April1993,p1251-1252。
优选的丹宁酶产生菌株属于植物乳杆菌种并具有在胃肠(GI)道中存活的能力。在这种环境中存活意味着所述菌株能在胃肠道中代谢和扩增(生活)一段时间。
根据优选方面,本发明涉及以下新菌株,它们都已于2002年11月28日保藏于德意志微生物保藏中心并已给予保藏号,即植物乳杆菌HEAL 9,DSM 15312,植物乳杆菌HEAL 19,DSM 15313,和植物乳杆菌HEAL 99,DSM 15316,以及它们的具有基本相同REA模式的变体。
所述新菌株已从健康成人结肠粘膜中分离并经在Rogosa琼脂上培养而筛选。所述菌株随后已由REA表征。
根据另一方面,本发明也涉及与丹宁组合的产生丹宁酶的植物乳杆菌菌株在制备药物中的用途,所述药物用于预防或治疗性处理心血管疾病、炎症性肠病(IBD)、肠激惹综合征(IBS)、胃肠道感染、糖尿病、癌症、阿尔茨海默病或具有自身免疫起源的疾病。产生丹宁酶菌株的实例是所述新菌株HEAL 9、HEAL 19和HEAL 99,以及已知菌株植物乳杆菌299,DSM 6595和植物乳杆菌299v,DSM 9843。
用于本发明组合物的产生丹宁酶的细菌的量优选不少于109cfu/剂·天。
根据另一方面,本发明涉及与丹宁一起的产生丹宁酶的植物乳杆菌菌株在食物保存中的用途。产生丹宁酶的菌株的实例是所述新菌株HEAL 9、HEAL 19和HEAL 99,以及已知菌株植物乳杆菌299,DSM 6595和植物乳杆菌299v,DSM 9843。所述菌株然后将在降解丹宁后直接在食品中产生防腐剂。通过向产品中补充纯丹宁组分或通过向产品中补充天然的、不太确定的、富含丹宁的添加剂,例如玫瑰果、红高粱或由松树内部皮层制造的粉。
能够丹宁的乳杆菌菌株和丹宁的混合物可以为治疗目的或作为保健作用而给予,从而降低以下疾病的风险因素:心血管疾病、代谢综合征、糖尿病、炎症性肠病(IBD)、肠激惹综合征(IBS)、胃肠道感染或与自身免疫起源有关的疾病。
与菌株植物乳杆菌299v,DSM 9843相比较,菌株植物乳杆菌HEAL9、HEAL 19和HEAL 99具有更高的粘附到人结肠粘膜细胞上的能力。
试验
分离菌株
42株不同的、新分离的乳杆菌菌株被测试并与熟知的参考益生菌株植物乳杆菌299v,DSM 9843比较它们产生丹宁酶即降解丹宁的能力。所述菌株列于下表1。
筛选方法
应用的检测丹宁酶活性的方法较以前被Osawa和Walsh(1993)描述。检测原理是用以下程序测量丹宁,没食子酸甲酯的降解:
待测细菌于MRS-琼脂(Merck,Darmstadt,Germany)上在37℃下厌氧培养2天,然后收获细胞并悬于5ml 0.9%(w/v)NaCl中。离心细胞悬液并将细胞重悬于10ml 0.9%NaCl中,测量620nm下的吸光度(0.9%NaCl溶液作标准)。细胞悬液稀释到吸光度在0.1到0.6之间(分光光度计,Pharmacia LKB,Novaspec II)。离心后细胞重悬于1ml没食子酸甲酯缓冲液(3.7g/l没食子酸甲酯[Aldrich Chemical Company,Inc.,Milwaukee,WI,USA],4.5g/lNaH2PO4,pH=5.0[无菌过滤])中并将试管在37℃保温24小时。加入1ml NaHCO3缓冲液(42g/l NaHCO3,pH=8.6)并在室温保温溶液1小时,然后测量440nm的吸光度(NaHCO3缓冲液作标准)。肉眼观察测量悬液颜色。
被分级为阳性丹宁酶活性的颜色应该是棕色或绿色。通过与没食子酸甲酯保温开始时细胞悬液的吸光度(A620;细胞量)比与没食子酸甲酯一起保温24小时后的吸光度(A440;在碱性溶液中暴露于氧后游离没食子酸显色)的比值而获得丹宁酶活性的定量值。
结果
具有丹宁酶活性的乳杆菌菌株筛选结果表示于表1。多数测试菌株不具有任何丹宁酶活性。然而,11个菌株是阳性的并在表1中给出。
表1.不同乳杆菌菌株中的丹宁酶活性。
生物 | 菌株 | 丹宁酶活性*(阳性或阴性) | 定量丹宁酶活性**(A440/A620) |
植物乳杆菌 | 299vDSM 9843 | + | 6.2 |
植物乳杆菌 | LP2 | + | 4.9 |
植物乳杆菌 | LP5 | + | 3.3 |
植物乳杆菌 | 4LF:1 | + | 6.1 |
植物乳杆菌 | 17LF:1 | + | 5.4 |
植物乳杆菌 | HEAL 9DSM 15312 | + | 6.4 |
植物乳杆菌 | HEAL 19DSM 15313 | + | 7.4 |
植物乳杆菌 | HEAL 99DSM 15316 | + | 6.8 |
*阳性丹宁酶活性显示为绿色到棕色。在长时间暴露于碱性溶液中的氧后细胞悬液中的游离没食子酸显色。
**丹宁酶活性,表达为与没食子酸甲酯保温24小时的开始时细胞悬液在620nm的吸光度(A620)比与没食子酸甲酯一起保温后(A440)在440nm的吸光度(A440)的比值。
丹宁酶阳性的植物乳杆菌菌株中的三株比熟知的益生菌株植物乳杆菌299v,DSM 9843具有更高的丹宁酶活性,即植物乳杆菌HEAL 9、植物乳杆菌HEAL 19和植物乳杆菌HEAL 99。它们已经从健康人肠粘膜中分离。
用REA进行基因型鉴定
根据Sthl M,Molin G,Persson A,AhrnéS & Sthl S,International Journal of Systematic Bacteriology,40:189-193,1990,并由Johansson,M-L,et al.,International Journal ofSystematic Bacteriology,45:670-675,1995进一步发展的方法,经限制性内切酶分析-REA-方法,检查所述菌株的染色体DNA切割模式。示意性REA可描述如下:制备本研究中菌株的染色体DNA并经限制性内切酶切割。0.75μg每种DNA分别在37℃用10单位EcoRI和HindIII消化4小时;分别使用每种内切酶。使用浸没的水平的琼脂糖板状凝胶经凝胶电泳根据大小分离切割的DNA片段。凝胶由150ml0.9%琼脂糖(超纯DNA级;低电内渗;BioRad Laboratories,Richmond,USA)组成并制成板状凝胶(150×235mm)。0.2μg高分子量DNA标记物(Bethesda Research Laboratories,MD,USA)与0.5μgDNA分子量标记物VI(Roche,Germany)被用作标准。通过加在Ficoll上样缓冲液(2g Ficoll,8ml水,0.25%溴酚蓝)中的样品DNA达到最小带变形和最大清晰度。
凝胶在恒压40V在约6-8℃电泳18小时。电泳期间缓冲液(89mMTris,23mM H3PO4,2mM EDTA钠盐,pH8.3)进行循环。随后凝胶在溴化乙锭(2μg/ml)中染色20分钟并在蒸馏水中脱色,用UV投射仪(UVP Inc.,San Gabriel,USA)在302nm显像并拍照。对于一直低到分子量1.2×106,这种进行凝胶电泳的方法产生良好分布和相对良好分离的带。
分析结果见附图。
粘附到HT-29细胞
在从人粘膜分离的总共32株植物乳杆菌菌株中,测试它们粘附到具有甘露糖特异性结合的人结肠癌细胞系HT-29的肠上皮细胞的能力(方法描述于Wold,A,et al.,Infection and Immunity,Oct.1988,p.2531-2537)。人结肠癌细胞系HT-29的细胞培养于补充10%胎牛血清、2mML-谷氨酰胺和50μg/ml庆大霉素的Eagle’s培养基(SigmaChemical Co.,Saint Louis,Mo,USA)。细胞达到汇合几天后用含EDTA的缓冲液(0.54mM)分离细胞,洗涤并以5×106/ml重悬于Hank’s平衡盐溶液(HBSS)。收获细菌,洗涤并以5×109/ml(2x在597nm的光密度1.5)重悬于HBSS中。细胞、细菌和HBSS以1∶1∶3混合并在4EC中端到端旋转保温30分钟。用冰冷PBS洗涤细胞一次并用中性缓冲的福尔马林(Histofix,Histolab,Gtebrog,Sweden)固定。与至少40个细胞中的每一个连接的细菌数目用干涉相衬显微镜(500×放大倍数,Nicon Optophot,带干涉相衬装置,BergstrmInstruments,Gtebrog,Sweden)确定并计算每个细胞的平均细菌数。
除了三株HEAL菌株以外所有菌株的值在0.3-14(在盐溶液中的粘附;在存在甲基甘露糖苷下对应值分别是0.5和2.4)之间。多数菌株的值低于10。结果在下表2中给出。
表2
生物 | 菌株 | 盐溶液中与HT-29细胞的粘附(细菌数/细胞) | 存在甲基甘露糖苷时的粘附 |
植物乳杆菌 | 299vDSM 9843 | 11.7 | 3.4 |
植物乳杆菌 | HEAL 9 | 20 | 2.1 |
植物乳杆菌 | HEAL 99 | 20 | 2.0 |
植物乳杆菌 | HEAL 19 | 23 | 5.0 |
植物乳杆菌 | ATCC 14917T | 5.2 | 2.2 |
植物乳杆菌 | 78B | 0.3 | 0.5 |
实验小鼠模型中的测试
方法
15只Balb/C小鼠分成5组(3只小鼠/组)并喂饲不同组合的正常食物、玫瑰果粉末(富含丹宁)和丹宁酶阳性菌株植物乳杆菌299v。所述成分与一些水混合得到糊状密度。第1和第2组给予正常小鼠食物,第3组给予添加玫瑰果粉末(1.6g/天)的正常食物,第4组给予添加植物乳杆菌299v(1010细菌/剂)的正常食物,第5组给予同时添加玫瑰果粉末和植物乳杆菌299v的正常食物。所述小鼠每天饲喂一次持续6-8天,然后诱导缺血/再灌注损伤。根据以下解剖方案制造损伤:皮下给予小鼠0.15ml氯胺酮/甲苯噻嗪溶液(分别7.85mg/ml和2.57mg/ml)进行麻醉。在腹部中线作切口并用无创导管环和止血钳封闭肠系膜上动脉。为液体复苏,将1.0ml PBS注射入腹膜腔。封闭动脉30分钟,然后去除导管环和止血钳并观察组织的立即再灌注。然后用vicryl 3-0缝合线关闭腹部。等待动物从麻醉中苏醒并从暖垫上取下放回笼中。4小时15分钟后,再次麻醉动物并按以下顺序获得组织和粪便样品放入预先称重的试管中:肝组织、回肠系膜组织和盲肠粪便用于细菌学取样,和盲肠和回肠组织用于脂质过氧化的比色测试,和盲肠和回肠组织用于组织学检查。称重用于细菌学评价的样品并放入冷冻介质中立即在-70℃冷冻。在PBS中漂洗用于比色测试的样品(LP0586)、称重、匀浆、等分然后立即在-70℃冷冻。
分析方法
通过在Rogosa琼脂(Merck,Darmstadt,Germany)上37℃培养3天、VRBD琼脂(Merck,Darmstadt,Germany)上37℃培养24小时和脑心灌注琼脂(BHI,Oxoid,Basingstoke,Hampshire,England)上37℃培养3天进行厌氧培养(BBL Gas Pak Plus,BectonDickinson and Company,Sparks,MD,USA),用活菌计数进行细菌学评价。BHI上的活菌计数也在有氧条件下进行。
在分光光度计和分析试剂盒BioxytechLP0-586TM(Oxis ResearchTM,Oxis Health Products,Inc.,Portland)的帮助下进行脂质过氧化的比色测试。根据制造商的说明进行分析。
脂质过氧化是非常明确的细胞损伤机制并用作细胞和组织中氧化应激的指标。脂质过氧化物不稳定并分解形成一系列复杂化合物包括活性羰基化合物。多不饱和脂肪酸过氧化物经过分解产生malondialdehyde(MDA)和4-hydroxyalkenals(HAE)。测量MDA可用作脂质过氧化的指标。LPO-586TM是设计用于定量MDA的比色测试并基于发色试剂N-甲基-2-苯基吲哚与MDA在45℃的反应。一分子MDA与两分子N-甲基-2-苯基吲哚反应产生最大吸光度在586nm的稳定发色物质。
结果
测量不同处理小鼠中的作为malondialdehyde(MDA)/g结肠组织测量的脂质过氧化,结果表示于表3。缺血/再灌注增加MDA。与阳性对照(第2组)比较,用食物中的玫瑰果粉末(第3组)或植物乳杆菌299v(第4组)预处理小鼠降低MDA。然而,玫瑰果粉末和植物乳杆菌299v组合预处理的作用更加显著降低MDA(第5组)。
表3.小鼠中缺血/再灌注后的脂质过氧化
小鼠组 | malondialdehyde(MDA)/g结肠组织(中值) |
第1组.对照A;未损伤(无缺血/再灌注);正常食物 | 4.3 |
第2组.对照B;正常食物 | 6.3 |
第3组.正常食物+玫瑰果粉末(RHP) | 5.1 |
第4组.正常食物+植物乳杆菌299v | 5.8 |
第5组.正常食物+RHP+植物乳杆菌299v | 3.6 |
活菌计数的结果表示于表4。缺血/再灌注损伤使BHI和Rogosa琼脂上的活菌计数增加因数10(比较第1组和第2组)。与其它饲养替代物比较,单独玫瑰果粉末(第3组)导致更低的活菌计数。除了肠杆菌科更低以外,同时给予植物乳杆菌299v和玫瑰果粉末的组(第5组)显示与不给予玫瑰果粉末的缺血/再灌注组(第2和4组)相同的活菌计数。然而,在允许乳杆菌生长的基质(第5组)上的活菌计数主要是植物乳杆菌299v。
表4.小鼠中缺血/再灌注后盲肠中的细菌群落
小鼠 | 活菌计数中值(CFU/g盲肠含量) | |||
总厌氧菌 | 总需氧菌 | 乳杆菌 | 肠杆菌科 | |
第1组.对照A;未损伤(无缺血/再灌注);正常食物 | 2×108 | 1×108 | 5×108 | 3×103 |
第2组.对照B;正常食物 | 3×109 | 1×109 | 1×109 | 4×103 |
第3组.正常食物+玫瑰果粉末(RHP) | 1×108 | 4×108 | 1×108 | <102 |
第4组.正常食物+植物乳杆菌299v | 3×109 | 4×109 | 2×109 | 3×103 |
第5组.正常食物+RHP+植物乳杆菌299v | 4×109 | 2×109 | 3×109 | <102 |
结论
玫瑰果中的丹宁降低损伤小鼠的肠中的细菌总负载,但当给予玫瑰果的同时给予小鼠植物乳杆菌299v则可减轻这种降低并且丹宁诱导的减少被植物乳杆菌299v补充。因此,丹宁支持肠菌群平衡而有利于益生菌株。给予玫瑰果粉末减轻脂质过氧化但这种作用被与玫瑰果粉末一起存在的植物乳杆菌299v增强。
与植物乳杆菌299v相比,菌株植物乳杆菌HEAL 9、HEAL 19和HEAL 99具有更高丹宁酶活性并且另外粘附到人结肠粘膜细胞上的能力比植物乳杆菌299v更高。
Claims (14)
1.含有与丹宁组合的一种或多种产生丹宁酶的植物乳杆菌或紧密相关乳杆菌种的菌株的组合物,其中所述菌株具有粘附到人肠粘膜上的能力。
2.根据权利要求1的组合物,其中另外含有载体。
3.根据权利要求1或2的组合物,其特征在于是食物组合物。
4.根据权利要求1或2的组合物,其特征在于是药物组合物。
5.根据权利要求1-4任意一项的组合物,其中包含产生丹宁酶的植物乳杆菌菌株。
6.产生丹宁酶的植物乳杆菌或紧密相关乳杆菌种的菌株,所述菌株具有粘附到人肠粘膜上的能力,其特征在于具有用Osawa和Walsh描述的方法确定的丹宁酶活性,其中排除菌株:植物乳杆菌299,DSM6595和植物乳杆菌299v,DSM 9843。
7.根据权利要求6的产生丹宁酶的菌株,所述菌株是植物乳杆菌HEAL 9,DSM 15312或其具有基本相同的REA模式的变体。
8.根据权利要求6的产生丹宁酶的菌株,所述菌株是植物乳杆菌HEAL 19,DSM 15313或其具有基本相同的REA模式的变体。
9.根据权利要求6的产生丹宁酶的菌株,所述菌株是植物乳杆菌HEAL 99,DSM 15316或其具有基本相同的REA模式的变体。
10.与丹宁组合的产生丹宁酶的植物乳杆菌或紧密相关乳杆菌种的菌株在制备药物中的用途,其中所述菌株具有粘附到人肠粘膜上的能力,所述药物用于预防或治疗性处理心血管疾病、糖尿病、炎症性肠病(IBD)、肠激惹综合征(IBS)、胃肠道感染、癌症、阿尔茨海默病或具有自身免疫起源的疾病。
11.根据权利要求10的产生丹宁酶的菌株的用途,所述菌株选自植物乳杆菌HEAL 9,DSM 15312,植物乳杆菌HEAL 19,DSM 15313,植物乳杆菌HEAL 99,DSM 15316,及其具有基本相同REA模式的变体。
12.与丹宁组合的产生丹宁酶的植物乳杆菌或紧密相关乳杆菌种的菌株在食品保存中的用途,其中所述菌株具有粘附到人肠粘膜上的能力。
13.根据权利要求12的产生丹宁酶的菌株的用途,所述菌株选自植物乳杆菌HEAL 9,DSM 15312,植物乳杆菌HEAL 19,DSM 15313,植物乳杆菌HEAL 99,DSM 15316,植物乳杆菌299v,DSM 9843,及其具有基本相同REA模式的变体。
14.与丹宁组合的产生丹宁酶的植物乳杆菌或紧密相关乳杆菌种的菌株在生产新食物中的用途,其中所述菌株具有粘附到人肠粘膜上的能力。
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE0300994-1 | 2003-04-04 | ||
SE0300994A SE527555C2 (sv) | 2003-04-04 | 2003-04-04 | Anti-inflammatorisk komposition innehållande tannasproducerande Lactobacillusstammar |
SE03009941 | 2003-04-04 | ||
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PCT/SE2004/000509 WO2004087893A1 (en) | 2003-04-04 | 2004-04-02 | Compositions comprising lactobacillus plantarum strains in combination with tannin and new lactobacillus plantarum strains |
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JP (1) | JP4731469B2 (zh) |
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