CN112877233A - 一种瑞士乳杆菌菌株及其应用 - Google Patents
一种瑞士乳杆菌菌株及其应用 Download PDFInfo
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- CN112877233A CN112877233A CN202110094046.4A CN202110094046A CN112877233A CN 112877233 A CN112877233 A CN 112877233A CN 202110094046 A CN202110094046 A CN 202110094046A CN 112877233 A CN112877233 A CN 112877233A
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- lactobacillus helveticus
- strain
- lactobacillus
- helveticus
- flora
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Abstract
本公开提供一株环境来源的益生菌,经过对菌株形态学特征、生理生化特征、分子生物学特征的分析鉴定,所述菌株为瑞士乳杆菌(Lactobacillushelveticus),将其命名为瑞士乳杆菌‑S。瑞士乳杆菌‑S能够耐酸、耐胆盐,表明其可以通过口服定殖于消化道;瑞士乳杆菌‑S无溶血性、对常用抗生素敏感性高,表明其无肠道致病力且不扩散抗生素耐受性基因;动物模型试验表明瑞士乳杆菌‑S能够改善肠道菌群结构和功能、提高肠道菌群多样性、降低炎症相关菌群的丰度,具有治疗腹泻便溏,改善脾虚症候的作用。
Description
技术领域
本发明属于微生物技术领域,涉及一株分离的益生菌菌株及其用途,特别涉及一株由草原牧场分离的瑞士乳杆菌-S株及其在改善肠道菌群结构和功能、治疗脾虚中的用途。
背景技术
益生菌是人和动物肠道、呼吸道、生殖道及皮肤黏膜系统的正常菌群,许多研究成果发现益生菌和肠黏膜共同组成保护屏障,防止病毒、细菌等的入侵。Hentges等(1983)认为正常菌群的主要作用是阻止入侵微生物在肠道中建群。Gaskin等(1996)报道认为正常菌群可刺激动物机制的发育从而增强机体免疫。正常菌群分泌的各种抗菌物质如细菌素能抑制某些厌氧菌繁殖。此外,正常菌群与病原微生物在建群点,营养等生存条件上存在的竞争关系,也在抑制病原微生物的生长发育和繁殖。人类越来越清晰地认识到益生菌对人类和动物生命健康的强大作用,大量现代免疫学研究结果已经证实益生菌对动物细胞免疫、体液免疫及肠黏膜局部免疫的调节功能,以及对免疫系统发育和免疫稳态的必不可少的决定作用。
益生菌还可以调节黏膜的菌群分布,促使某些病原体发生凝聚,并阻止其粘附在黏膜上,以防止其进一步的侵入,并且益生菌吸附在黏膜表面(包括肠黏膜和呼吸道黏膜),能够降解粘性蛋白并利用这种内源性的营养可以基本保持数量稳定,这种粘附可以与黏膜免疫系统发生相互作用,可以有效地刺激黏膜免疫系统,起到免疫调节作用,从而使黏膜免疫系统处于合适的稳定的激活状态(免疫稳态),非常有利于抵御外来病毒或细菌的入侵。因此通过乳酸菌的合理存在和适当刺激,可以提高黏膜免疫系统的防御功能,从而有效的阻止病毒的吸附和侵入。
益生菌一直被认为对人体健康是有益而无害的,然而最近几年不断有报道指出,益生菌可能成为抗生素抗性基因的病原库。它们能够将抗药性基因转移到致病菌上。一系列相关研究的结果表明,益生菌的抗药性非常令人担忧。Temmerman研究了55种欧洲的益生菌产品,从这些产品中分离出187株益生菌,其中有79%的菌株对卡那霉素产生抗性、65%抗万古霉素、26%抗四环素、23%抗青霉素G、16%抗红霉素、11%抗氯霉素,分离的菌株中有68.4%对多种抗生素有抗性。徐进等人研究发现,在来源保健食品的益生菌中,检测的12株益生菌,除动物双歧杆菌FDBb-12耐受2种抗生素外,其余菌株分别耐受3-9种常见抗生素,属于多重耐药菌。在2000-2006年发酵乳制品行业常用的137株益生菌菌种的抗生素药敏实验表明,其中的22株乳杆菌对萘啶酮酸、万古霉素和磷霉素的耐药率较高。益生菌中抗药菌株的出现和抗药性的传播,附带了许多不安全性的风险,在使用益生菌菌株的筛选、鉴定和使用中必需严格控制抗药基因的扩散风险。
发明内容
针对现有技术中益生菌改善肠道菌群、健脾止泻功能不强,存在抗药基因扩散隐患等技术问题,本发明提供一株天然牧场环境来源的益生菌,经过对菌株形态学特征、生理生化特征、分子生物学特征的分析鉴定,所述菌株为瑞士乳杆菌(Lactobacillushelveticus),将其命名为瑞士乳杆菌-S。瑞士乳杆菌-S能够耐酸、耐胆盐,表明其可以通过口服定殖于消化道;瑞士乳杆菌-S无溶血性、对常用抗生素敏感性高,表明其无肠道致病力且不扩散抗生素耐受性基因;动物模型试验表明瑞士乳杆菌-S能够改善肠道菌群结构和功能、提高肠道菌群多样性、降低炎症相关菌群的丰度,具有治疗腹泻便溏,改善脾虚症候的作用。
具体而言,一方面,本发明提供一种瑞士乳杆菌(Lactobacillus helveticus)菌株,其特征在于该菌株的16S rDNA序列为SEQ ID NO:1。
进一步,本发明所述瑞士乳杆菌(Lactobacillus helveticus)菌株,其特征在于该菌株能够以葡萄糖、果糖、半乳糖、甘露糖、乳糖、麦芽糖、海藻糖为碳源,不能以葡萄糖酸、甘露醇、山梨醇、棉子糖、鼠李糖、阿拉伯糖、木糖、蔗糖为碳源。
进一步,本发明所述瑞士乳杆菌(Lactobacillus helveticus)菌株,其特征在于该菌株耐酸、耐胆盐、不溶血,对氨苄西林、阿莫西林、头孢噻肟、卡那霉素、庆大霉素、诺氟沙星、四环素、氯霉素、万古霉素、克林霉素敏感。
进一步,本发明所述瑞士乳杆菌(Lactobacillus helveticus)菌株,其为2020年08月07日保藏于中国微生物菌种保藏管理委员会普通微生物中心,保藏编号为CGMCCNo.20504的瑞士乳杆菌-S株。
另一方面,本发明提供一种组合物,其特征在于包括本发明前述任一瑞士乳杆菌(Lactobacillus helveticus)菌株。
进一步,本发明所述的组合物,其特征在于所述组合物还包括选自下组的组分:一种或多种其他微生物、益生元、一种或多种营养物质。
进一步,本发明所述的组合物,其特征在于所述一种或多种其他微生物为益生菌,包括选自乳酸杆菌,双歧杆菌,芽孢杆菌,丙酸杆菌,链球菌,乳球菌,片球菌,肠球菌,葡萄球菌,酵母或其任何组合的菌株;所述一种或多种营养物质选自能对受试者的健康起到有益影响的组分,包括蛋白质,碳水化合物,脂类物质,矿物质,维生素,植物成分,氨基酸,免疫调节剂,乳汁替代物,或其任何组合。
另一方面,本发明提供一种药物组合物,其包含本发明前述任一瑞士乳杆菌(Lactobacillus helveticus)菌株或本发明前述任一所述的组合物,以及药学上接受的辅料;
优选地,所述药物组合物为丸剂、粉剂、胶囊剂、片剂、颗粒粉剂、盖膜剂、口溶性颗粒剂、糖衣丸剂或液体剂的形式。
另一方面,本发明提供前述任一瑞士乳杆菌(Lactobacillus helveticus)菌株、本发明前述任一所述的组合物、本发明前述药物组合物在制备治疗腹泻、便溏、或脾虚症候群药物中的用途。
另一方面,本发明提供前述任一瑞士乳杆菌(Lactobacillus helveticus)菌株、本发明前述任一所述的组合物、本发明前述药物组合物在制备改善肠道菌群结构和功能、提高肠道菌群多样性、降低炎症相关菌群丰度的药物或食品中的用途。
为更好理解本发明,首先定义一些术语。其他定义则贯穿具体实施方式部分而列出。
术语“益生菌”被定义为任何非致病的细菌,并且将其以活菌向宿主施用足够数量时,能够对宿主的健康起到有益影响。
在某些实施方案中,所述细菌选自乳酸杆菌属,双歧杆菌属,芽孢杆菌属,丙酸杆菌属,链球菌属,乳球菌属,片球菌属,肠球菌属,葡萄球菌属,或其任何组合。
在某些实施方案中,所述双歧杆菌属的细菌选自:动物双歧杆菌(Bifidobacterium animalis),两歧双歧杆菌(Bifidobacterium bifidum),短双歧杆菌(Bifidobacterium breve),婴儿双歧杆菌(Bifidobacterium infantis),长双歧杆菌(Bifidobacterium longum),青春双歧杆菌(Bifidobacterium adolescentis),或其任何组合。
在某些实施方案中,所述乳杆菌属的细菌选自:副干酪乳杆菌(Lactobacillusparacasei),嗜酸乳杆菌(Lactobacillus acidophilus),短乳杆菌(Lactobacillusbrevis),詹氏乳杆菌(Lactobacillus jensenii),惰性乳杆菌(Lactobacillus iners),干酪乳杆菌(Lactobacillus casei),卷曲乳杆菌(Lactobacillus crispatus),弯曲乳杆菌(Lactobacillus curvatus),德氏乳杆菌(Lactobacillus delbrueckii),发酵乳杆菌(Lactobacillus fermentum),加氏乳杆菌(Lactobacillus gasseri),瑞士乳杆菌(Lactobacillus helveticus),约氏乳杆菌(Lactobacillus johnsonii),植物乳杆菌(Lactobacillus plantarum),罗伊氏乳杆菌(Lactobacillus reuteri),鼠李糖乳杆菌(Lactobacillus rhamnosus),清酒乳杆菌(Lactobacillus sakei),唾液乳杆菌(Lactobacillus salivarius),或其任何组合。
在某些实施方案中,所述芽孢杆菌属的细菌选自:枯草芽孢杆菌(Bacillussubtilis),凝结芽孢杆菌(Bacillus coagulans),或其任何组合。
在某些实施方案中,所述丙酸杆菌属的细菌选自:谢氏丙酸杆菌(Propionibacterium shermanii),费氏丙酸杆菌(Propionibacterium freudenreichii),产丙酸丙酸杆菌(Propionibacterium acidipropionici),或其任何组合。
在某些实施方案中,所述链球菌属的细菌选自:嗜热链球菌(Streptococcusthermophilus),唾液链球菌(Streptococcus salivarius),或其任何组合。
在某些实施方案中,所述乳球菌属的细菌为乳酸乳球菌(Lactococcus lactis)。
在某些实施方案中,所述肠球菌属的细菌选自:粪肠球菌(Enterococcusfaecalis),屎肠球菌(Enterococcus faecium),或其任何组合。
在某些实施方案中,所述酵母选自酿酒酵母(Saccharomyces cerevisiae),布拉氏酵母(Saccharomyces boulardii),马克斯克鲁维酵母(Kluyveromyces marxianus),或其任何组合。
术语“药学上可接受的载体”是指在药理学和/或生理学上与受试者和活性成分相容的载体,其是本领域公知的(参见例如Remington'sPharmaceutical Sciences.Editedby Gennaro AR,19th ed.Pennsylvania:MackPublishing Company,1995),并且包括但不限于:pH调节剂,表面活性剂,佐剂,离子强度增强剂。例如,pH调节剂包括但不限于磷酸盐缓冲液;表面活性剂包括但不限于阳离子,阴离子或者非离子型表面活性剂,例如Tween-80;离子强度增强剂包括但不限于氯化钠。
术语“药物”涵盖了人类医学和兽医学中供人类和动物两者使用的药物,同时涵盖了用于掺入动物饲料(例如牲畜饲料和/或宠物食物)中的药物。此外,本文中所使用的术语“药物”意指提供治疗、预防和/或有益效果的任何物质。本文中所使用的术语“药物”不一定限于需要上市许可证(Marketing Approval)的物质,而是包括可以用于化妆品、保健品、食物(包括例如饲料和饮料)、益生菌培养物和膳食补充剂的物质。
术语“定殖”包括细菌或其它微观生物体的非暂时性居留。
术语“患者”、“受试者”和“个体”可以互换使用,并且指人或非人动物。这些术语包括哺乳动物,例如人,非人灵长类动物,家畜(例如牛、猪、绵羊、山羊、家禽),伴侣动物(例如犬、猫、马、兔)和啮齿动物(例如小鼠和大鼠)。在某些实施方式中,该术语是指人患者。在示例性实施方式中,该术语是指患有例如2型糖尿病、高血糖症、高胰岛素血症、肥胖症,胃肠道炎性病症(例如IBD)或其任何组合的人患者。
如本文所用,术语“肠”是指整个胃肠道或消化道(也称为消化道),并且是指多细胞动物内的器官系统,该多细胞动物摄取食物,消化它以提取能量和营养,并排出剩余的废物。如本文所用,术语“胃肠道”是指从口腔到直肠的整个消化道。术语“胃肠道”包括但不限于嘴,并延续到食道、胃、小肠、大肠、直肠以及最后是肛门。
术语“治疗(treatment)”(也称为“治疗(treat)”或“治疗(treating)”)是指根据治疗性方案的治疗性试剂的任何施用,所述治疗性方案达到所需效果,即部分或完全减轻、改善、缓解、抑制、延迟发作、降低严重程度和/或降低特定疾病、障碍和/或病症的一种或多种症状或特征(例如改善肠道菌群结构和功能、提高肠道菌群多样性、降低炎症相关菌群丰度、治疗腹泻、便溏、或脾虚症候群)的发生率;在一些实施方式中,根据治疗性方案的治疗性试剂的施用与所需效果的实现相关。这种治疗可以针对没有表现出相关疾病、障碍和/或病症的受试者和/或针对仅表现出疾病、障碍和/或病症的早期迹象的受试者。替代地或另外地,这种治疗可以针对表现出相关疾病、障碍和/或病症的一种或多种所确定迹象的受试者。在一些实施方式中,治疗可以针对已被诊断患有相关疾病、障碍和/或病症的受试者。在一些实施方式中,治疗可以针对已知具有一种或多种易感因素的受试者,所述易感因素在统计学上与相关疾病、障碍和/或病症发展的风险增加相关。
术语“益生元”,prebiotics是由格伦·吉布索(G.R.Gibsion)等(1995)提出,是指“不易消化的食物成分,它可以通过选择性地刺激结肠中的一种或少数几种细菌的生长或活性而对宿主产生有益影响,从而增进宿主健康”。益生元应是在通过上消化道时,大部分不被消化而能被肠道菌群所发酵的。最重要的是它只是刺激有益菌群的生长,而不是有潜在致病性或腐败活性的有害细菌。最基本的益生元为碳水化合物,但定义并不排除被用作益生元的非碳水化合物物质:理论上来讲,任何可以减少有害菌种,而有益于促进健康的菌种或活动的物质都可以叫作益生元。包括有功能性低聚糖类(如低聚果糖、低聚木糖、低聚半乳糖、低聚异麦芽糖等)、多糖类(现阶段所发现的微藻如螺旋藻、节旋藻等)、一些天然植物(如蔬菜、中草药、野生植物等)的提取物、蛋白质水解物、多元醇等。功能性低聚糖是最常见的益生元。
本发明的上述技术方案,相比现有技术具有以下优点:
(1)本发明所述的瑞士乳杆菌-S安全性高。瑞士乳杆菌-S分离自内蒙古呼伦贝尔牙克石天然草场采集的土壤,天然草场环境中人工施用的抗生素少,获得的瑞士乳杆菌-S对常用抗生素的耐药性少,无多重耐药性,长期使用不会导致耐药基因的扩散。另外,瑞士乳杆菌-S不产生溶血素,体外培养不产生溶血环,应用于人体或动物体不产生致病性。
(2)本发明所述的瑞士乳杆菌-S耐酸、耐胆盐,能够通过口服到达并定殖于肠道。益生菌要发挥益生作用就必须通过胃部,进入肠道,能够耐受酸性环境是益生菌存活的重要条件。胆盐能破坏细胞膜,减少益生菌的存活率,益生菌到达肠道后能否生存在很大程度上取决于其对胆盐的耐受能力。瑞士乳杆菌-S在人工胃液和人工肠液中的存活率分别达89.7%、87.5%,具有作为益生菌应用的前景。
(3)本发明所述的瑞士乳杆菌-S能够改善肠道菌群结构和功能、提高肠道菌群多样性、降低炎症相关菌群丰度,在小鼠模型中对于腹泻、便溏等脾虚症候群具有显著改善和治疗效果。瑞士乳杆菌-S种属分类属于常用的益生菌种类,既能用于制备食品(包括保健食品或功能食品),也可用于制备药物。
附图说明
通过阅读下文优选实施方式的详细描述,各种其他的优点和益处对于本领域普通技术人员将变得清楚明了。附图仅用于示出优选实施方式的目的,而并不认为是对本发明的限制。而且在整个附图中,用相同的参考符号表示相同的部件。在附图中:
图1:瑞士乳杆菌-S革兰氏染色光学镜检形态。
图2:不同组小鼠肠道菌群物种相对丰度柱形累加图。
具体实施方式
下面将参照附图更详细地描述本公开的示例性实施方式。虽然附图中显示了本公开的示例性实施方式,然而应当理解,可以以各种形式实现本公开而不应被这里阐述的实施方式所限制。相反,提供这些实施方式是为了能够更透彻地理解本公开,并且能够将本公开的范围完整的传达给本领域的技术人员。
实施例1:瑞士乳杆菌-S的分离、培养与鉴定
在内蒙古呼伦贝尔牙克石天然草场采集的土壤中筛选益生菌。培养条件:MRS培养基,37℃厌氧培养。
MRS培养基为固体或液体培养基,MRS液体培养基配方为:酪蛋白胨10.0g/L,牛肉膏10.0g/L,酵母粉5.0g/L,葡萄糖5.0g/L,乙酸钠5.0g/L,柠檬酸二铵2.0g/L,Tween 801.0g/L,K2HPO4 2.0g/L,MgSO4·7H2O 0.2g/L,MnSO4·H2O 0.05g/L,CaCO3 20.0g/L,pH6.8。MRS固体培养基配制方法为MRS液体培养基中添加琼脂15.0g/L。
分离筛选方法如下:
1、取样:用取样铲,将表层5cm左右的浮土除去,取5~25cm处的土样10~25g,装入事先准备好的塑料袋。
2、倒平板:配置的MRS固体培养基在高压灭菌锅内灭菌,灭菌后融化的MRS固体培养基在超净工作台中倒平板。
3、制备土壤稀释液:称取1g土壤,倒入装有99ml无菌水的锥形瓶中,震荡摇晃均匀。从制成的土壤悬液中吸取0.5ml,注入装有4.5ml无菌水的无菌试管中,吹打均匀。
4、涂布:在超净工作台中,每个浓度的溶液吸取100μl溶液,使用无菌涂布棒在MRS固体培养基平板上均匀涂布,并做好标记。每个浓度涂布3个平板。
5、将平板倒置放入37℃培养箱中厌氧培养48小时。
6、划线分离:使用接种环从培养的平板上挑取单菌落在新的MRS固体培养基平板上进行划线分离。
7、重复操作5-6步3次。
8、菌种鉴定:分离的单菌落在MRS液体培养基中培养,并进行16S测序鉴定。
9、配制斜面培养基:向灭菌后的试管中倒入适量融化的MRS固体培养基,再次灭菌后,制成斜面培养基。
10、接种斜面培养基:使用接种环从培养的平板上挑取单菌落在斜面培养基上进行划线分离。
11、将试管放入37℃培养箱中厌氧培养48小时。
经过上述分离筛选、鉴定方法获得一株益生菌,对其培养形态和镜检特征、代谢和生化特征、遗传和分子生物学特征进行鉴定。
所述益生菌的培养形态和镜检特征如下:MRS固体培养基中生长形态为白色圆形菌落,直径约2毫米,表面润湿光滑,边缘整齐。革兰氏染色呈阳性,显微镜下观察呈长杆状,长约3-6微米,宽约0.6微米,单个和成链,无鞭毛,不运动(图1)。
采用生理生化试验分析其糖代谢特征,生化鉴定结果如表1所示:
表1生理生化特征结果
对益生菌的分子生物学特征进行鉴定,所述益生菌的16s rDNA序列测序结果如SEQ ID NO:1所示。
ctggctcaggacgaacgctggcggcgtgcctaatacatgcaagtcgagcgagcagaaccagcagatttacttcggtaatgacgctggggacgcgagcggcggatgggtgagtaacacgtggggaacctgccccatagtctgggataccacttggaaacaggtgctaataccggataagaaagcagatcgcatgatcagcttataaaaggcggcgtaagctgtcgctatgggatggccccgcggtgcattagctagttggtaaggtaacggcttaccaaggcaatgatgcatagccgagttgagagactgatcggccacattgggactgagacacggcccaaactcctacgggaggcagcagtagggaatcttccacaatggacgcaagtctgatggagcaacgccgcgtgagtgaagaaggttttcggatcgtaaagctctgttgttggtgaagaaggatagaggtagtaactggcctttatttgacggtaatcaaccagaaagtcacggctaactacgtgccagcagccgcggtaatacgtaggtggcaagcgttgtccggatttattgggcgtaaagcgagcgcaggcggaagaataagtctgatgtgaaagccctcggcttaaccgaggaactgcatcggaaactgtttttcttgagtgcagaagaggagagtggaattccatgtgtagcggtggaatgcgtagatatatggaagaacaccagtggcgaaggcgactctctggtctgcaactgacgctgaggctcgaaagcatgggtagcgaacaggattagataccctggtagtccatgccgtaaacgatgagtgctaagtgttgggaggtttccgcctctcagtgctgcagctaacgcattaagcactccgcctggggagtacgaccgcaaggttgaaactcaaaggaattgacgggggcccgcacaagcggtggagcatgtggtttaattcgaagcaacgcgaagaaccttaccaggtcttgacatctagtgccatcctaagagattaggagttcccttcggggacgctaagacaggtggtgcatggctgtcgtcagctcgtgtcgtgagatgttgggttaagtcccgcaacgagcgcaacccttgttattagttgccagcattaagttgggcactctaatgagactgccggtgataaaccggaggaaggtggggatgacgtcaagtcatcatgccccttatgacctgggctacacacgtgctacaatggacagtacaacgagaagcgagcctgcgaaggcaagcgaatctctgaaagctgttctcagttcggactgcagtctgcaactcgactgcacgaagctggaatcgctagtaatcgcggatcagaacgccgcggtgaatacgttcccgggccttgtacacaccgcccgtcacaccatggaagtctgcaatgcccaaagccggtggcctaaccttcgggaaggagccgtctaaggcagggcagatgactggggtgaagtcgtaacaaggtagccgtag
根据培养形态和镜检特征、生化鉴定结果、16s rDNA序列比对分析结果,确定所述益生菌为一株瑞士乳杆菌(Lactobacillus helveticus),将其命名为瑞士乳杆菌-S,于2020年08月07日保藏于北京市朝阳区北辰西路1号院3号中国科学院微生物研究所(邮编100101,电话010-64807355)中国微生物菌种保藏管理委员会普通微生物中心,保藏编号为CGMCC No.20504。
实施例2:瑞士乳杆菌-S的胃酸、胆盐耐受性
瑞士乳杆菌-S菌株在MRS液体培养基中活化后,以5%接种量转接MRS液体培养基,37℃厌氧培养24小时后,6000rpm离心5分钟收集菌体,用PBS(pH7.2)洗菌体2次并最终用PBS(pH7.2)重悬菌体并调整菌浓度至1×108CFU/mL。取上述菌悬液50毫升且平均分为5份,6000rpm离心5分钟收集菌体,分别用10毫升PBS(pH7.2)、PBS(pH2.5)、胆盐溶液、人工胃液、人工肠液重悬菌体,37℃条件下厌氧培养2小时,培养前后分别进行平板计数,计算菌体存活率。结果如表2所示。
表2瑞士乳杆菌-S在不同条件下的存活率
由表2的结果可知,与PBS(pH7.2)组相比,瑞士乳杆菌-S菌株耐酸耐胆碱性能良好,在人工胃液和人工肠液中存活率较高,具备应用潜力。
PBS(pH7.2)配方为:K2HPO4 0.21g/L,Na2HPO4·7H2O 0.73g/L,NaCl 9.00g/L,pH7.2。
PBS(pH2.5)配方为:K2HPO4 0.70g/L,NaCl 9.00g/L,稀磷酸调pH至2.5。
胆盐溶液配制方法为:向PBS(pH7.2)中加入0.5%牛胆盐(w/v)。
人工胃液配制方法为:取1M稀盐酸16.4mL,加水约800mL及胃蛋白酶10g,搅匀后加水定容至1000mL即可。
人工肠液配制方法为:取磷酸二氢钾6.8g加水500mL,用0.4%的氢氧化钠溶液调节pH至6.8;另取胰酶10g加水适量使溶解,将两液混合后,加水定容至1000mL即可。
实施例3:瑞士乳杆菌-S的溶血性和耐药性
1.溶血性测试:瑞士乳杆菌-S划线接种于绵羊血平板,37℃培养箱中培养24小时后观察菌落周围是否出现溶血环。测试血平板上无溶血环出现,表明瑞士乳杆菌-S菌株无溶血性。
2.抗生素敏感性测试:瑞士乳杆菌-S菌株悬液浓度调整至1×109CFU/mL,取1mL菌悬液加入到无菌培养皿中,培养皿中再加入融化后降温至45℃左右的MRS固体培养基,混匀后水平放置。待凝固后,将药敏纸片放置在平板表面,置于37℃培养箱中培养24小时,用游标卡尺测定抑菌圈直径,试验结果参照美国临床和实验室标准协会(CLSI)制定的《抗菌药物敏感性实验执行标准》(2010年版)判定菌株的药物敏感性。用大肠杆菌(Escherichiacoli)ATCC25922和金黄色葡萄球菌(Staphylococcus aureus)ATCC25923作为质控菌株。测试结果如表3所示。
表3瑞士乳杆菌-S菌株的抗生素敏感性测试结果
注:S,敏感;I,中等;R,耐药
实施例4:瑞士乳杆菌-S的健脾止泻功能
1.动物分组与造模
60只健康雄性SD小鼠,8周龄,体重20±2g,随机分为3组(正常组、模型组、试验组),每组20只。动物饲养于通风橱屏障环境,室温20~26℃,各组均采用生长繁殖鼠饲料喂养。适应性饲养1周后,开始造模。正常组每天灌胃0.4mL蒸馏水,模型组和试验组均每天灌胃0.4mL大黄煎液,连续灌胃7天建立脾虚模型。与正常组相比,模型组和试验组小鼠大便变稀,体重增加缓慢,毛色干枯无光泽,活动减少,表明建模成功。
2.菌株干预
脾虚模型建立后,3组小鼠每天灌胃2次,第一次按照造模时的方案进行,第一次灌胃后8h进行第二次灌胃,方案为正常组和模型组0.2mL蒸馏水,试验组0.2mL瑞士乳杆菌-S菌悬液(浓度为1×109CFU/mL)。连续灌胃7天后,小鼠称重,取粪便置于无菌离心管中,液氮保存。之后小鼠禁食24小时(正常饮水),灌胃0.5mL半固体营养糊。30分钟后颈椎脱臼处死,取脾脏和小肠。脾脏称重并计算脾指数,脾指数=脾脏重量/小鼠体重。小肠用于测量小肠推进率,小肠幽门至回盲肠为全长,幽门至炭末最远处为推进长度,小肠推进率(%)=推进长度/全长×100%。试验结果表明瑞士乳杆菌-S能显著改善小鼠脾虚症状,使小鼠恢复正常(表4)。
表4瑞士乳杆菌-S菌株健脾功能动物试验
实施例4:瑞士乳杆菌-S改善肠道菌群结构和功能
将上述实施例4中液氮保存的小鼠粪便用干冰保存送北京诺禾致源科技股份有限公司进行菌群测定,采用Illumina NovaSeq测序平台进行双末端测序,测序区域为16SrDNAV4区。根据物种注释结果,选取每个样品和分组在属水平上最大丰度排名前30的物种,生成物种相对丰度柱形累加图(如图2所示)。与正常组相比,模型组小鼠肠道菌群多样性降低,另枝菌属(Alistipes)和乳杆菌属(Lactobacillus)丰度显著降低,与炎症相关的拟杆菌属(Bacteroides)、丹毒丝菌属(Erysipelatoclostridium)和埃希氏菌属(Escherichia)丰度显著提高。与模型组相比,试验组小鼠肠道菌群多样性显著提高,肠道菌群结构得到恢复,另枝菌属和乳杆菌属丰度显著提高,且与炎症相关的拟杆菌属、丹毒丝菌属、埃希氏菌属丰度显著降低。由结果可知,保藏号为CGMCC No.20504的瑞士乳杆菌-S能显著改善脾虚小鼠肠道菌群结构。
以上所述,仅为本发明较佳的具体实施方式,但本发明的保护范围并不局限于此,任何熟悉本技术领域的技术人员在本发明揭露的技术范围内,可轻易想到的变化或替换,都应涵盖在本发明的保护范围之内。因此,本发明的保护范围应以所述权利要求的保护范围为准。
Claims (10)
1.瑞士乳杆菌(Lactobacillus helveticus)菌株,其特征在于该菌株的16S rDNA序列为SEQ ID NO:1。
2.如权利要求1所述瑞士乳杆菌(Lactobacillus helveticus)菌株,其特征在于该菌株能够以葡萄糖、果糖、半乳糖、甘露糖、乳糖、麦芽糖、海藻糖为碳源,不能以葡萄糖酸、甘露醇、山梨醇、棉子糖、鼠李糖、阿拉伯糖、木糖、蔗糖为碳源。
3.如权利要求1所述瑞士乳杆菌(Lactobacillus helveticus)菌株,其特征在于该菌株耐酸、耐胆盐、不溶血,对氨苄西林、阿莫西林、头孢噻肟、卡那霉素、庆大霉素、诺氟沙星、四环素、氯霉素、万古霉素、克林霉素敏感。
4.如权利要求1所述瑞士乳杆菌(Lactobacillus helveticus)菌株,其为2020年08月07日保藏于中国微生物菌种保藏管理委员会普通微生物中心,保藏编号为CGMCC No.20504的瑞士乳杆菌-S株。
5.一种组合物,其特征在于包括权利要求1-4中任一所述瑞士乳杆菌(Lactobacillushelveticus)菌株。
6.如权利要求5所述的组合物,其特征在于所述组合物还包括选自下组的组分:一种或多种其他微生物、益生元、一种或多种营养物质。
7.如权利要求6所述的组合物,其特征在于所述一种或多种其他微生物为益生菌,包括选自乳酸杆菌,双歧杆菌,芽孢杆菌,丙酸杆菌,链球菌,乳球菌,片球菌,肠球菌,葡萄球菌,酵母或其任何组合的菌株;所述一种或多种营养物质选自能对受试者的健康起到有益影响的组分,包括蛋白质,碳水化合物,脂类物质,矿物质,维生素,植物成分,氨基酸,免疫调节剂,乳汁替代物,或其任何组合。
8.一种药物组合物,其包含权利要求1-4任一所述的瑞士乳杆菌(Lactobacillushelveticus)菌株或权利要求5-7任一所述的组合物,以及药学上接受的辅料;优选地,所述药物组合物为丸剂、粉剂、胶囊剂、片剂、颗粒粉剂、盖膜剂、口溶性颗粒剂、糖衣丸剂或液体剂的形式。
9.权利要求1-4任一所述的瑞士乳杆菌(Lactobacillus helveticus)菌株、权利要求5-7任一所述的组合物、或权利要求8所述药物组合物在制备治疗腹泻、便溏、或脾虚症候群药物中的用途。
10.权利要求1-4任一所述的瑞士乳杆菌(Lactobacillus helveticus)菌株、权利要求5-7任一所述的组合物、或权利要求8所述药物组合物在制备改善肠道菌群结构和功能、提高肠道菌群多样性、降低炎症相关菌群丰度的药物或食品中的用途。
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CN116790448A (zh) * | 2023-08-21 | 2023-09-22 | 新益(天津)生物科技有限责任公司 | 一株能够缓解便秘和腹泻的瑞士乳杆菌opb102和应用 |
CN116790448B (zh) * | 2023-08-21 | 2024-01-12 | 新益(天津)生物科技有限责任公司 | 一株能够缓解便秘和腹泻的瑞士乳杆菌opb102和应用 |
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