CN114990004B - 一种分泌型免疫球蛋白a包裹态罗伊氏乳杆菌及防治妊娠糖尿病的应用 - Google Patents
一种分泌型免疫球蛋白a包裹态罗伊氏乳杆菌及防治妊娠糖尿病的应用 Download PDFInfo
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Abstract
本发明公开了一种分泌型免疫球蛋白A包裹态罗伊氏乳杆菌及防治妊娠糖尿病的应用,属于微生物技术和食品科学领域。本发明的罗伊氏乳杆菌QS01可预防和/或辅助治疗妊娠糖尿病,具体体现在:(1)显著抑制孕中、晚期妇女餐后血糖异常升高;(2)显著抑制孕中、晚期妇女餐后血糖曲线下面积异常升高;(3)显著预防妊娠期间发生胰岛素抵抗;(4)显著预防妊娠期间肠道黏膜屏障损伤和慢性炎症发生诱发的妊娠糖尿病。
Description
技术领域
本发明涉及一种分泌型免疫球蛋白A包裹态罗伊氏乳杆菌及防治妊娠糖尿病的应用,属于微生物技术和食品科学领域。
背景技术
妊娠期糖尿病(GDM)的发病率与产科人群中超重和肥胖的增加同步增加。GDM与不良的孕产妇和新生儿结局相关。患有GDM的女性发生先兆子痫和剖宫产分娩的风险增加。产妇GDM也会增加巨大儿、肩难产、新生儿低血糖和新生儿产后进入重症监护室的风险。此外,GDM与母亲和及子代远期发生2型糖尿病、肥胖、高血压、代谢综合征等疾病风险明显增加,并且在再次妊娠时,该母亲再发生GDM的风险也会明显增加。
孕前超重和肥胖的女性患GDM的风险更高,这部分人群患GDM的危险性是正常体重人群的1.3~4.8倍。目前,GDM治疗的重点是控制血糖,这可以防止或减少短期并发症的影响,但不能减少长期并发症的的影响。预防GDM是最佳选择。很多研究者已经探索了不同的GDM预防策略,包括使用二甲双胍、生活方式干预、补充益生菌、肌醇和维生素D。就理论而言,孕前减肥和生活方式干预是预防GDM的最佳策略,但大部分人难以坚持。
近年来有研究者指出,肠道菌群可能与GDM的发生、发展存在密切联系。多项研究显示,GDM孕妇的肠道菌群构成与正常孕妇存在显著差异,相较于正常孕妇,GDM孕妇肠道菌群中的机会致病菌明显增多,而双歧杆菌和乳杆菌等有益菌明显降低。妊娠糖尿病患者表现出肠道分泌型免疫球蛋白A包裹的罗伊氏乳杆菌耗竭的情况,且与她们肠道黏膜屏障功能损伤有关。GDM女性在妊娠早期存在肠道黏膜屏障损伤情况,表现为血液连蛋白(Zonulin)水平显著升高。GDM女性肠道革兰氏阴性菌增殖,其释放的脂多糖会造成肠道黏膜屏障损伤,使脂多糖等细菌成分进入血液循环,引起低度炎症,干扰胰岛素信号传导和血糖水平调节,最终导致葡萄糖耐受受损。益生菌作为有益于宿主健康的活的微生物,能够通过调节肠道菌群的结构及其代谢产物改善肠道微生态,进而调节宿主的代谢及免疫功能,减轻炎症反应。益生菌能够调节2型糖尿病患者的血糖代谢,进而有效改善血糖控制,在2型糖尿病的治疗和管理中发挥积极作用。有研究显示,在妊娠14至16周期间补充鼠李糖乳杆菌HN001可降低GDM患病率(dio:10.1017/S0007114517000289),尤其是在老年妇女和既往GDM患者中。但罗伊氏乳杆菌预防GDM的作用目前尚不清楚。
由于伦理因素,GDM干预在人体难以开展。动物模型是评价益生菌预防GDM的主要手段。过往研究已经用低剂量的链脲佐菌素结合高蔗糖和高脂肪饮食以及其他因素诱导了GDM(doi:10.1155/2016/9704607)。也有研究者用高脂饲料饲喂的母鼠诱导GDM(doi:10.1016/j.metabol.2009.10.015),但这些模型诱导症状不是进行性葡萄糖耐受不良,不是典型的GDM症状。最近有研究者建立了一种饮食诱导的妊娠期葡萄糖不耐受进行性小鼠模型,可很好地模拟人类GDM症状(10.1113/JP278570.)。这种模型将怀孕的F0代小鼠用蛋白含量为8%的饲料饲养(正常含量为21%),其子代妊娠后会在妊娠期出现自发的GDM症状。这种模型对评价和开发预防GDM的益生菌具有重要应用价值。
发明内容
本发明要解决的技术问题是提供一种新的可预防或辅助治疗妊娠糖尿病的药物。
本发明提供了一种罗伊氏乳杆菌(Lactobacillus reuteri)QS01,已于2020年10月22日保藏于广东省微生物菌种保藏中心,保藏编号为GDMCC No.61217,保藏地址为广州市先烈中路100号大院59号楼5楼。
所述罗伊氏乳杆菌(Lactobacillus reuteri)QS01是通过先针对分泌型免疫球蛋白A(sIgA)结合共生菌的生理特征,利用免疫磁珠法从江苏无锡的孕早期健康孕妇的粪便富集sIgA结合菌群,再根据罗伊氏乳杆菌对万古霉素的抗性和高温可培养特性定向分离得到的。
所述罗伊氏乳杆菌(Lactobacillus reuteri)QS01在MRS琼脂培养基上的菌落为圆形、光滑、白色,直径约1mm。
所述罗伊氏乳杆菌(Lactobacillus reuteri)QS01具有以下特性:
(1)在pH为3.5的环境中停留2h后的存活率高于85%;
(2)在浓度分别为3g/kg和4g/kg胆汁溶液中停留4h后的存活率分别高于80%和65%;
(3)可耐受45℃高温。
(4)粘附素粘液的本发明还提供了含有所述罗伊氏乳杆菌QS01的组合物。
在一种实施方式中,所述组合物中罗伊氏乳杆菌的含量≥1×108CFU/g或1×108CFU/mL。
在一种实施方式中,所述罗伊氏乳杆菌QS01的形态是活细菌、失活的细菌,和/或含有发酵产物和/或代谢物的形式,或上述任一状态的混合物。
本发明还提供了所示罗伊氏乳杆菌(Lactobacillus reuteri)QS01在制备预防和/或辅助治疗妊娠糖尿病的产品中的应用。
在一种实施方式中,所述产品的适用对象为妊娠糖尿病人群,或具有妊娠糖尿病潜在危险因素的人群;所述潜在危险因素包括但不限于:产前体质指数大于24kg/m2,且孕周小于12~24周的孕妇,有妊娠糖尿病史、有糖尿病家族史、妊娠高血压、有死产史、多囊卵巢综合征、多胎产、孕妇年龄≥25岁、有早产史。
在一种实施方式中,所述产品包括但不限于药物。
在一种实施方式中,所述产品为益生菌制剂。
在一种实施方式中,所述产品中还含有sIgA。
在一种实施方式中,所述应用是从妊娠第12~14周开始服用罗伊氏乳杆菌(Lactobacillus reuteri)QS01。
在一种实施方式中,所述应用是针对产前体质指数大于24kg/m2,且孕周小于12~24周的孕妇,于妊娠任何阶段开始服用罗伊氏乳杆菌(Lactobacillus reuteri)QS01。
在一种实施方式中,所述产品以不低于1×104CFU罗伊氏乳杆菌QS01的日剂量提供给孕妇。
在一种实施方式中,所述产品中罗伊氏乳杆菌QS01的含量不低于1×104个细胞/mL。
在一种实施方式中,所述罗伊氏乳杆菌QS01的形态是活细菌、失活的细菌,和/或含有发酵产物和/或代谢物的形式,或上述任一状态的混合物。
在一种实施方式中,所述产品为药品,其剂型包括但不限于:片剂、颗粒剂、胶囊剂、粉剂、油剂、液体或液体。
在一种实施方式中,所述药品还包括药学上可接受的赋型剂;所述药学上可接受的赋型剂是指任何可用于药学领域的稀释剂、辅助剂和/或载体。
有益效果:
1、本发明筛选出了一种罗伊氏乳杆菌(Lactobacillus reuteri)Q S01,此罗伊氏乳杆菌(Lactobacillus reuteri)QS01可预防和/或辅助治疗妊娠糖尿病,具体体现在:
(1)抑制餐后血糖异常升高和抑制胰岛素抵抗指数升高;
(2)抑制肠道黏膜屏障损伤和慢性炎症。
2、分泌型免疫球蛋白A(sIgA)有益菌被sIgA结合包裹后可屏蔽细菌表面抗原,阻止其诱导过强炎性反应,本发明筛选得到的罗伊氏乳杆菌(Lactobacillus reuteri)QS01可与分泌型免疫球蛋白A(sIgA)相结合,因此,表现出抗炎特性。
3、本发明筛选得到的罗伊氏乳杆菌(Lactobacillus reuteri)QS01在pH为3.5的环境中停留2h后的存活率高于85%,在浓度分别为3g/kg、和4g/kg胆汁溶液中停留4h后的存活率分别高于80%和65%,可耐受45℃高温,具有良好的生理特性。
生物材料保藏
一株罗伊氏乳杆菌(Lactobacillus reuteri)QS01,分类学命名为Lactobacillusreuteri,已于2020年9月28日保藏于广东省微生物菌种保藏中心,保藏编号为GDMCC No:61217,保藏地址为广州市先烈中路100号大院59号楼5楼。
附图说明
图1:孕早期健康孕妇(50例)、孕晚期健康孕妇(50例)和妊娠糖尿病患者(21例)的分泌型免疫球蛋白A包裹菌群构成的线性判别分析(A)和其中罗伊氏乳杆菌的组间差异(B)。
图2:低蛋白饲料诱导小鼠妊娠糖尿病流程图。
图3:二甲双胍、罗伊氏乳杆菌QS01预防妊娠糖尿病的作用;其中:A,口服血糖耐量测试期间血糖变化曲线;B,血糖曲线下面积;C,胰岛素抵抗指数(n=8)。柱上不同字母表示差异显著,p<0.05,与GDM组比较;采用单因素方差分析进行比较,随后进行Tukey多重比较;CON,对照组;HFD,妊娠糖尿病对照组;GDM-HN001,鼠李糖乳杆菌HN001处理的妊娠糖尿病组;HFD-MET,二甲双胍处理的妊娠糖尿病组;HFD-QS01,罗伊氏乳杆菌QS01处理的妊娠糖尿病组。
图4:二甲双胍、罗伊氏乳杆菌QS01预防妊娠糖尿病小鼠肠道黏膜屏障损伤的作用;其中:A,血浆连蛋白;B,血浆脂多糖;C,血浆脂多糖结合蛋白(LBP)(n=8)。柱上不同字母表示差异显著,p<0.05,与GDM组比较;采用单因素方差分析进行比较,随后进行Tukey多重比较。CON,对照组;HFD,妊娠糖尿病对照组;GDM-HN001,鼠李糖乳杆菌HN001处理的妊娠糖尿病组;HFD-MET,二甲双胍处理的妊娠糖尿病组;HFD-QS01,罗伊氏乳杆菌QS01处理的妊娠糖尿病组。
图5:二甲双胍、罗伊氏乳杆菌QS01预防妊娠糖尿病小鼠血浆白介素6(IL-6)和超敏C反应蛋白升高的作用;柱上不同字母表示差异显著,p<0.05,与GDM组比较;采用单因素方差分析进行比较,随后进行Tukey多重比较。CON,对照组;HFD,妊娠糖尿病对照组;GDM-HN001,鼠李糖乳杆菌HN001处理的妊娠糖尿病组;HFD-MET,二甲双胍处理的妊娠糖尿病组;HFD-QS01,罗伊氏乳杆菌QS01处理的妊娠糖尿病组。
图6:二甲双胍、罗伊氏乳杆菌QS01预防妊娠糖尿病小鼠胰腺β细胞数量降低的作用。柱上不同字母表示差异显著,p<0.05
具体实施方式
下面结合具体实施例对本发明进行进一步的阐述。
下述实施例中作为对照菌株的鼠李糖乳杆菌HN001获取自新西兰乳品研究所,罗伊氏乳杆菌DSM17938获取自瑞典拜奥(BioGaia)公司。
下述实施例中涉及的培养基如下:
MRS琼脂培养基:蛋白胨10g/L、酵母提取物5g/L、葡萄糖20g/L、无水乙酸钠2g/L、柠檬酸氢二胺2g/L、K2HPO4·3H2O 2.6g/L、MgSO4·7H2O 0.5g/L、MnSO4·7H2O 0.25g/L、吐温-80 1g/L、琼脂20g/L、蒸馏水1000g/L。
MRS液体培养基(g/L):蛋白胨10g/L、酵母提取物5g/L、葡萄糖20g/L、无水乙酸钠2g/L、柠檬酸氢二胺2g/L、K2HPO4·3H2O 2.6g/L、MgSO4·7H2O 0.5g/L、MnSO4·7H2O 0.25g/L、吐温-80 1g/L、蒸馏水1000g/L。
实施例1:健康孕早期孕妇、孕晚期孕妇和GDM孕妇肠道sIgA包裹菌群构成的菌种水平比较
招募50名孕晚期健康孕妇、21名患妊娠糖尿病孕妇(妊娠期为37.36±3.09周)以及50名健康妊娠早期孕妇(妊娠期为10.98±1.39周)。采集志愿者粪便样本,按10%悬浮于磷酸盐缓冲液PBS(pH7.3),在1000g离心5min,收集上清液,在15000×g离心15min,收集沉淀(菌体)。将菌体按10%悬浮于蛋白胨缓冲液,加入0.5%牛血清白蛋白,加入生物素标记的兔抗人免疫球蛋白A血清,孵育15~30min,再加入链霉亲和素修饰磁珠(0.5mg/mL),用磁铁吸附菌体,用蛋白胨缓冲液洗两次,获得sIgA结合菌群。
用提取sIgA结合菌群基因组DNA,通过特异性引物PCR扩增原核生物16S rDNA V3-V4高变区。引物为上游:515F(5′-GTGCCAGCMGCCGCGGTAAN-3′)和下游806R(5′-GGACTACHVGGGTWTCTAAT-3′)。经扩增后产物末端带有Index的接头,通过Illumina MiSeq进行Paired-end测序。将每个样本的一对测序序列用FLASH软件组装成一条序列,剔除引物和条码序列,然后利用软件USEARCH的UNOISE算法将所有序列去噪生成ASV。用BLCA软件进行菌种水平注释。
结果显示,根据采用线性判别分析估算每个组分(物种)丰度对人群间菌群构成差异效果影响的大小。图1A显示,孕早期健康孕妇肠道sIgA包裹的优势菌属更为丰富,主要以梭菌为主,其次为乳杆菌科细菌,在菌种水平,罗伊氏乳杆菌是典型的高丰度种。孕晚期健康孕妇肠道sIgA包裹菌以拟杆菌和肠杆菌科细菌为主,而妊娠糖尿病个体的双歧杆菌占优势。图1B显示,sIgA包裹的罗伊氏乳杆菌在孕早期的含量显著高于孕晚期,期检出率分别为15/50和6/50。在孕晚期,健康个体的含量显著高于妊娠糖尿病个体,该菌种在妊娠糖尿病个体基本被耗竭了(检出率仅为1/21)。
实施例2:健康妊娠早期孕妇粪便sIgA结合态罗伊氏乳杆菌的分离
1)分离
在实施例1中,样本T1BNC9的sIgA包裹态罗伊乳杆菌含量最高,将该样本的IgA结合菌群在无菌条件下用PBS缓冲溶液(pH 6.8)梯度稀释,吸取合适的稀释度溶液(每mL含有100个左右细菌)100μL涂布于含有万古霉素(50μg/mL)的MRS琼脂培养基平板,平板倒置放入厌氧培养箱,45℃培养72h;挑取MRS琼脂培养基平板上不同形态的菌落进行划线分离,经37℃培养48h后,再次挑取MRS琼脂培养基平板上不同形态的单菌落进行划线分离,直至得到形态一致的纯的单菌落;挑取MRS琼脂培养基平板上的纯菌落接种于5mL MRS液体培养基中,37℃培养18h;取1mL菌液于无菌离心管中,8000r/min离心3min后弃去上层培养基,菌泥重悬于30%甘油溶液中置于-80℃中保藏,得到菌株。
2)鉴定
提取分离菌株的基因组DNA,进行PCR扩增16S rDNA,进行测序,将测序得到的结果在ezbiocloud中进行核酸序列比对,其中,有一株菌的核苷酸序列与罗伊氏乳杆菌(Lactobacillus reuteri)JCM 1112的相似性达到99.72%,判定此菌株为罗伊氏乳杆菌,命名为罗伊氏乳杆菌(Lactobacillus reuteri)QS01。
3)培养
将罗伊氏乳杆菌(Lactobacillus reuteri)QS01接入MRS琼脂培养基平板上37℃培养36~72h后,观察其菌落,发现其菌落为圆形、光滑、白色,直径约1mm。
将罗伊氏乳杆菌(Lactobacillus reuteri)QS01置于pH为3.5的生理盐水中停留2h,发现其在pH为3.5的环境中停留2h后的存活率为85%,高于LGG和罗伊氏乳杆菌DSM17938。
将罗伊氏乳杆菌(Lactobacillus reuteri)QS01分别置于浓度为3g/kg、和4g/kg胆汁溶液中停留4h,发现其在浓度分别为3g/kg、和4g/kg胆汁溶液中停留4h后的存活率分别高于80%和65%,高于鼠李糖乳杆菌HN001。
将罗伊氏乳杆菌(Lactobacillus reuteri)QS01接入MRS液体培养基中,分别于35、40、45、50℃培养36~72h后,观察其生长曲线,发现其可耐受45℃高温,于35~45℃的温度范围内均能良好生长。
表1罗伊氏乳杆菌QS01和鼠李糖乳杆菌HN001耐酸性、耐胆盐性抗热性(存活率)
菌株 | pH3.5 | 3g/kg胆盐 | 4g/kg胆盐 | 45℃培养 |
鼠李糖乳杆菌HN001 | 80% | 78% | 60% | - |
罗伊氏乳杆菌QS01 | 85% | 80% | 65% | +++ |
罗伊氏乳杆菌DSM17938 | 81% | 78% | 64% | + |
注:耐酸性在pH为3.5的PBS孵育2h后前、后测定活菌,根据测定数值之比(孵育后/孵育前)计算存活率(%);在浓度分别为3g/kg、和4g/kg胆盐溶液中孵育4h前、后测定活菌数,根据测定数值之比(孵育后/孵育前)计算存活率。
实施例3:罗伊氏乳杆菌QS01预防妊娠糖尿病的应用
具体步骤如下:
1)菌悬液的制备:将罗伊氏乳杆菌QS01悬浮于无菌饮水,获得浓度为5×108cfu/mL菌悬液;鼠李糖乳杆菌HN001采用上述相同方法制备菌悬液。
2)动物实验分组
将6周龄C57BL/6小鼠饲养于控温SPF动物房,设置12h明暗循环,自由饮食。将雌、雄鼠按2:1同笼饲养,完成交配后次日将其分离。通过检查阴栓确定怀孕的第0天。在剩余妊娠期间,将雌鼠单独饲养。将其生产的雌性小鼠(F0代)分为两组,分别在整个妊娠和哺乳期用正常和低蛋白饲料饲养(表2)。在F1代雌性出生后第21天断奶,并用正常饲料饲养。在F1代雌性成熟期,与正常饲料饲喂的雄鼠按2:1合笼使其定时受孕(流程见图2)。
将受孕的F1代雌鼠分为四组(每组12只):
①健康对照组(CON):F0代和F1代雌鼠都用正常饲料饲喂;
②GDM对照组(GDM):F0代用低蛋白饲料饲喂,产生的F1代雌鼠用正常饲料饲喂;
③GDM+QS01处理(GDM+QS01):在GDM对照组的基础上,用QS01处理GDM组F0代雌鼠,具体为:从妊娠9天开始干预,饮水给予罗伊氏乳杆菌QS01菌悬液,
④GDM+鼠李糖乳杆菌HN001处理(阳性对照):在GDM对照组的基础上,用鼠李糖乳杆菌HN001处理GDM组F0代雌鼠,具体为:从妊娠9天开始干预,饮水给予鼠李糖乳杆菌HN001菌悬液,
⑤GDM+二甲双胍处理(药物对照):在GDM对照组的基础上,饮水给予5mg/mL的二甲双胍溶液。
表2动物饲料配方(g/100g)
2)测定指标
口服葡萄糖耐量试验:妊娠第17天,各组小鼠禁食过夜12h。在第19天进行口服葡萄糖耐量实验。测定小鼠的空腹血糖(0h),然后按2.0g葡萄糖/kg体重灌胃葡萄糖水溶液。在灌胃后0.5、1和2h,尾静脉取血,用血糖仪和血糖试纸测量血糖浓度。绘制血糖变化曲线,计算血糖曲线下面积,计算公式为:1/4×空腹血糖+1/2×0.5h血糖水平+4/3×1h血糖水平+2h血糖水平。
胰岛素抵抗指数:最后一次测定口服葡萄糖耐受实验的次日,二氧化碳窒息处死孕鼠,心脏穿刺采集血液。用超敏小鼠胰岛素ELISA试剂盒测定血清胰岛素和胰高血糖素。计算胰岛素抵抗指数:空腹血糖(nmol/L)×胰岛素(mU/L)/22.5。
黏膜屏障和慢性炎症:收集血样并在4℃、1,500×g、离心10min。参照ELISA试剂盒说明书检测血浆中连蛋白、脂多糖、脂多糖结合蛋白和IL-6的水平。
胰腺β细胞数量分析:采用免疫组织化学方法对胰岛素和Ki-67进行共定位。使用蔡司荧光显微镜观察载玻片,并使用ImageJ进行细胞计数分析。每个胰岛素表达细胞以20倍的速度成像,人工计数。在本研究中,一个“胰岛”包含大于5个β细胞,一个额外的胰岛“簇”包含1-5个β细胞。用免疫荧光免疫组织化学方法对胰岛素(β细胞),进行形态计量学分析。抗胰岛素抗体(1:200,抗小鼠,Abcam)将用于冰冻切片,在4℃孵育过夜。第二天,使用555和488荧光染料,将二抗敷于一抗,连同4,6-二脒基-2苯基吲哚复染细胞核。每个胰腺(n=4-6)至少两个切片(重复)计算β细胞质量。
所有数据以平均值±标准差(SD)表示,使用SPSS软件20.0版进行单因素方差分析(ANOVA)和Tukey多重比较检验,当数据齐性检验显著时使用自然对数转换后再进行比较。
3)实验结果
如图3所示,给小鼠灌胃葡萄糖后,约在15min血糖达到峰值。GDM组血糖峰值显著高于健康对照组小鼠,二甲双胍、罗伊乳杆菌QS01处理和鼠李糖乳杆菌HN001处理可显著抑制血糖升高(p<0.05)。GDM组的血糖曲线下面积显著高于健康对照组(P<0.01),二甲双胍处理组血糖曲线下面积回复健康状态,而QS01和HN001处理组,处理组血糖曲线下面积显著低于健康对照和GDM组,QS01的作用优于HN001(p<0.05)。GDM组小鼠的胰岛素抵抗指数显著高于健康对照组小鼠(P<0.001),二甲双胍、QS01和HN001处理组显著抑制了胰岛素抵抗指数升高(p<0.01),QS01的作用优于HN001(p<0.05)。
图4显示,发生妊娠糖尿病的小鼠存在明显的肠道黏膜屏障损伤情况,主要表现为血浆连蛋白、脂多糖和脂多糖结合蛋白(LBP)显著升高(p<0.05),罗伊氏乳杆菌QS01处理后,这三个指标都显著降低(p<0.05),QS01的作用优于HN001(p<0.05),说明QS01抑制了黏膜屏障损伤。
妊娠糖尿病小鼠血浆慢性炎症指标IL-6和超敏c反应蛋白显著升高(p<0.01),QS01和HN001处理显著抑制了IL-6升高(p<0.05),QS01抑制超敏c反应蛋白的作用优于HN001(p<0.05)(图5)。
利用免疫荧光技术定位胰腺中表达胰岛素的β细胞。结果显示,CON、MET及QS01组β细胞质量显著高于GDM组(P<0.05)。经计算,胰岛素的免疫荧光平均相对强度的趋势与β细胞质量相似,CON(P<0.001)和MET(P<0.05)组胰岛素平均荧光强度显著高于GDM组,益生菌处理显著提高了胰腺β细胞数量,QS01优于HN001(P<0.05)(图6)。
虽然本发明已以较佳实施例公开如上,但其并非用以限定本发明,任何熟悉此技术的人,在不脱离本发明的精神和范围内,都可做各种的改动与修饰,因此本发明的保护范围应该以权利要求书所界定的为准。
Claims (10)
1. 罗伊氏乳杆菌(Lactobacillus reuteri)QS01,已于2020年9月28日保藏于广东微生物菌种保藏中心,保藏编号为GDMCC No:61217,保藏地址为广东省广州市先烈中路100号大院59号楼5楼 。
2.含有权利要求1所述罗伊氏乳杆菌QS01的组合物。
3.根据权利要求2所述的组合物,其特征在于,所述组合物中罗伊氏乳杆菌的含量≥1×106CFU/g或1×106CFU/mL。
4.根据权利要求2或3所述的组合物,其特征在于,所述罗伊氏乳杆菌QS01的形态是活细菌、失活的细菌,或发酵产物、代谢物中的至少一种与活细菌的混合物,或发酵产物、代谢物中的至少一种与失活细菌的混合物。
5.权利要求1所述的罗伊氏乳杆菌QS01在制备预防和/或辅助治疗妊娠糖尿病的产品中的应用。
6.根据权利要求5所述的应用,其特征在于,所述产品的适用对象为患有妊娠糖尿病或具有妊娠糖尿病潜在危险因素的群体。
7. 根据权利要求6所述的应用,其特征在于,所述产品以不低于1×104 CFU罗伊氏乳杆菌QS01的日剂量提供给适用对象。
8.根据权利要求7所述的应用,其特征在于,所述应用是从妊娠第12~14周开始摄入罗伊氏乳杆菌QS01。
9.根据权利要求5~8任一所述的应用,其特征在于,产品包括药物。
10.权利要求1所述的罗伊氏乳杆菌QS01在制备发酵食品中的应用。
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