CN111714522A - 拟杆菌及其应用 - Google Patents
拟杆菌及其应用 Download PDFInfo
- Publication number
- CN111714522A CN111714522A CN201910160192.5A CN201910160192A CN111714522A CN 111714522 A CN111714522 A CN 111714522A CN 201910160192 A CN201910160192 A CN 201910160192A CN 111714522 A CN111714522 A CN 111714522A
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- Prior art keywords
- bacteroides
- cfu
- xylanisolvens
- fatty liver
- obesity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Abstract
本发明公开了拟杆菌在治疗和/或预防代谢相关疾病药品、保健品或食品中的应用。本发明提供的拟杆菌可以显著控制体重、改善血糖、血脂及非酒精性脂肪性肝病症状,可以用于制备治疗糖尿病、降血脂、肥胖及非酒精性脂肪性肝病的药品、保健品或食品。
Description
技术领域
本发明涉及微生物学技术领域。
背景技术
代谢疾病是由于体内代谢紊乱而发生的疾病的总称。代谢疾病通常是由碳水化合物、脂质、蛋白质、维生素、电解质、水等的失衡而引起的。代谢疾病的实例包括肥胖症、高血糖、高血脂症、动脉硬化症、高血压、非酒精性脂肪性肝病等。随着社会的发展,人们生活水平的不断提高和饮食结构的调整,饮食呈富余化趋势,导致代谢类疾病的发病率不断提高,其中以肥胖、高血糖以及高血脂最引人关注。肥胖是一系列疾病的诱导因子,如高血压、高血糖、冠心病、胆囊病、骨关节炎、睡眠中呼吸窒息。目前全世界糖尿病人数为2亿人左右,并以惊人的速度每年递增。中国糖尿病人数为4千万,占世界糖尿病人群总数的1/5。另外,因血脂升高导致的动脉粥样硬化、冠心病等心血管疾病发病率逐年升高,并有年轻化趋势。降血糖、降血脂药品已经成为药品研究的重点之一。
益生菌从发展到临床应用经历了多年的开发与探索,益生菌的类别、作用机制逐渐清晰,临床应用越发广泛,涉及内容包括脏器保护、免疫、抑菌、降血脂、降血糖、控制体重等。在我国,多种益生菌制剂在预防或治疗疾病方面显示了良好的前景,但是现阶段大多数研究规模小,所涉及益生菌一般局限在双歧杆菌 (Bifidobacterium spp.),乳酸杆菌(Lactobacillus spp.)等少数几个种属。
拟杆菌属肠道中的一类重要革兰氏阳性菌,并且部分研究表明其在肠道内的含量在糖尿病、肥胖、系统炎症患者、动物模型中降低,然而,没有研究发现其中常见种解木聚糖拟杆菌(Bacteroides xylanisolvens),多里氏拟杆菌(Bacteroides dorei),卵形拟杆菌(Bacteroides ovatus)对代谢性疾病的作用,对于其菌体是否可以缓解或治疗诸如肥胖,糖尿病,非酒精性脂肪肝等代谢疾病仍未见报道。
叶酸是由蝶啶、对氨基苯甲酸和L-谷氨酸组成的B族维生素,在生物体内一碳代谢过程中发挥着重要作用,一系列研究表明叶酸缺乏会引起肝脏脂肪累积,甘油三酯从头合成增加,系统炎症水平上调及机体氧化压力增加等,近期研究表明,低碳饮食可以通过调节人体菌群增加叶酸合成途径,继而改善非酒精性脂肪肝症状。我们发现拟杆菌在体内外均可以产生叶酸,进而影响肝脏脂代谢影响,缓解非酒精性脂肪性肝病症状。
发明内容
本发明的第一目的公开了拟杆菌在治疗和/或预防代谢相关疾病药品、保健品或食品中的应用。
进一步地,所述的代谢性疾病包括肥胖、高血糖、高血脂、非酒精性脂肪性肝病。
进一步地,所述的拟杆菌包括解木聚糖拟杆菌、多里氏拟杆菌、卵形拟杆菌及其发酵代谢物。
本发明的第二目的公开了一种拟杆菌菌剂在预防和/或治疗代谢性疾病的药品、保健品或食品中的应用,所述的菌剂包括益生菌和解木聚糖拟杆菌及其发酵代谢物;所述的益生菌包括氏乳杆菌、鼠李糖乳杆菌GM-020、丁酸梭菌、双歧杆菌中任何一种或多种。
本发明提供的拟杆菌及其菌剂可以显著控制体重、改善血脂,可以用于治疗肥胖、高血糖、高血脂、非酒精性脂肪性肝病的药品或食品中。
附图说明
图1是拟杆菌对高脂饲料诱导大鼠非酒精性脂肪性肝病的影响图。
图2是肝脏纤维化情况图。
图3是叶酸含量变化图。
具体实施方式
发明人经过广泛而深入的研究和实验,发现拟杆菌(Bacteroides)具有预防和治疗代谢相关疾病(包括肥胖、高血糖、高血脂、非酒精性脂肪性肝病)的作用,将含有拟杆菌(Bacteroides)的活性菌剂饲喂实验对象,发现该菌剂能够抑制体重增加,降低血糖,降低血脂、改善非酒精性脂肪性肝病,有效减轻糖尿病及肥胖等病症。
本发明提供了拟杆菌(Bacteroides)在治疗和预防代谢相关疾病方面的用途。
受试者摄入高脂肪的食物,解木聚糖拟杆菌(Bacteroides xylanisolvens,简写:BX),多里氏拟杆菌(Bacteroides dorei,简写:BD),卵形拟杆菌(Bacteroides ovatus,简写:BO)均具有抑制该受试者体重增加的能力。
根据本发明的一个优选例,经菌株BX,BD,BO来治疗的被喂以可导致肥胖的高脂肪食物的C57BL/6J小鼠以及肥胖模型ob/ob小鼠,与未受治疗的对照组相比,可保持体重无任何增加,且有助于血糖、血脂下降,非酒精性脂肪性肝病症状的改善。因此,所述拟杆菌能够用以预防和治疗肥胖及由肥胖引起的疾病如糖尿病、非酒精性脂肪性肝病等。
本发明还提供了一种菌剂,其含有有效量的拟杆菌(Bacteroides),在一个优选例中,所述菌剂还包括选自下组的益生菌:加氏乳杆菌(Lactobacillus gasseri)、鼠李糖乳杆菌GM-020(PL60)、丁酸梭菌菌株(Clostridium butyricum)、双歧杆菌菌株(Bifidobacterium lactis BB12)及其组合。
本发明菌剂可以以药品片剂、针剂或胶囊的任一种形式给药,所述药品制剂包括赋形剂、药品允许的媒介和载体,这些物质可根据给药途径进行选择。本发明中的药品制剂还包含辅助的组分。
其中,乳糖、葡萄糖、蔗糖、山梨糖醇、甘露糖、淀粉、阿拉伯胶、磷酸钙、藻酸盐、明胶、硅酸钙、细结晶纤维素、聚乙烯吡咯烷酮(PVP)、纤维素、水、糖浆、甲基纤维素、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石、硬脂酸镁或矿物油等都可用作本发明中药品的载体、赋形剂或稀释剂等。
此外,本发明的药品菌剂进一步包括润滑剂、润湿剂、乳化剂、悬乳液稳定剂、防腐剂、甜味剂和香料等。本发明的药品菌剂可通过多种公知的方法以肠衣制剂生产,以便于药品组合物的活性成分即微生物能顺利通过胃而不被胃酸所破坏。
本发明的药品制剂可制成肠衣片供口服使用。
本发明中的“肠衣”包括所有常规药品允许使用的包衣,这些包衣不被胃酸降解,但在小肠中能充分分解并快速释放出本发明的微生物。本发明的肠衣能在合成胃酸如pH=1的HCl溶液中36-38℃维持2小时以上,并优选在合成肠液如 pH=7.0的缓冲液中在1.0小时内分解。本发明的肠衣以每片约16-30mg进行包衣,较佳地16-25mg,更佳地16-20mg进行包衣。本发明中肠衣厚度为5-100μm,理想的厚度为20-80μm,肠衣成分自己公开知晓的常规聚合物。
下述实施例中所使用的实验方法如无特殊说明,均为常规方法。
下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
实施例1
拟杆菌(Bacteroide)的分离纯化
采用无菌操作,用载玻片刮去健康志愿者新鲜粪便50mg,置于盛有9mL 无菌生理盐水的玻璃试管中,充分震荡摇匀,然后吸取0.5mL混合液于盛有 4.5mL无菌生理盐水的试管中,此稀释度为10-1,重复以上过程作10倍比稀释,至10-6稀释度,选择10-4,10-5,10-6三个稀释度,吸取0.1mL菌液滴于MRS培养基平板上,平板涂布后采用厌氧培养法(5%CO2)将涂好的培养皿置37℃培养箱培养48h。
采用四分区划线法,用接种环挑取形态不同的菌落在MRS琼脂培养基上进行划线分离培养,经48h培养后,在四分区中挑取分离效果好的菌落用接种环接种于MRS斜面培养基上作纯培养,重复传代培养3次,而后置于4℃冰箱保存备用。
对纯培养进行16S RNA测序确定菌种,得到解木聚糖拟杆菌(Bacteroidesxylanisolvens),多里氏拟杆菌(Bacteroides dorei),卵形拟杆菌(Bacteroides ovatus)三种菌株。
实施例2
拟杆菌(Bacteroides)对肥胖、糖尿病模型小鼠ob/ob血糖、血脂及体重影响
材料:
被测菌株为:解木聚糖拟杆菌(Bacteroides xylanisolvens,简写:BX)、多里氏拟杆菌(Bacteroides dorei,简写:BD)、卵形拟杆菌(Bacteroides ovatus,简写:BO)。
灌胃菌量定为0.15mL/10g体重,菌浓为1×107cfu/mL,浓缩后浓度为1× 109cfu/mL,频率为每日一次。
菌液需提前培养,每周活化保证新鲜,并分别测定浓度。
Ob/ob小鼠购自中国医学科学院北京协和医学院动物研究所,温度20-24摄氏度,恒湿50-60%,光照12小时(8:00-20:00),隔音,自由摄食、饮水,适应环境一周后进行实验。
血糖试纸(罗氏公司)、血糖仪(罗氏公司)、血清总胆固醇TC试剂盒(批号20131112),低密度脂蛋白LDL-C试剂盒(批号20140114),高密度脂蛋白 HDL-C试剂盒(批号20140413),甘油三酯TG试剂盒(批号20131226)购自南京建成生物工程研究所。
方法:雄性C57小鼠6-8周,体重30-32,10只,作为正常对照组(1),雄性ob/ob小鼠6-8周,体重38-42,测定空腹血糖,依据血糖值和体重情况平均分组:(2)模型对照组,(3)BX1×109cfu/mL,(4)BD 1×109cfu/mL,(5)BO 1×109cfu/mL,每组8只,连续给药5周。
模型对照组给予等量的厌氧PBS。各组小鼠分别灌胃给与0.15mL/10g体重的菌液,连续5周,对照组和模型组给予等量的生理盐水。
末次给药后,取血,4摄氏度3000rpm离心,测定血清总胆固醇TC,低密度脂蛋白LDL-C,甘油三酯TG。
结果:与对照组和模型组比较,BX,BD,BO菌株都可以显著控制体重,从第 1周起即可降低自由饮食血糖及禁食(4小时)血糖,改善小鼠血脂情况,结果见表1-4。
表1拟杆菌菌株(BX,BD,BO)对高血糖小鼠ob/ob的体重影响
表2拟杆菌菌株(BX,BD,BO)对高血糖小鼠ob/ob的自由饮食血糖影响
表3拟杆菌菌株(BX,BD,BO)对高血糖小鼠ob/ob的禁食血糖影响
表4拟杆菌菌株(BX,BD,BO)对高血糖小鼠ob/ob的血脂影响
实施例3
解木聚糖拟杆菌(Bacteroides xylanisolvens)及其益生菌组合物对高血糖小鼠ob/ob血糖、体重、血脂及肝功能的影响
材料:
被测菌株为解木聚糖拟杆菌(Bacteroides xylanisolvens,简写:BX),加式乳杆菌(Lactobacillus gasseri),鼠李糖乳杆菌(lactobacillus rhamnosu GM-020),丁酸梭菌菌株(Clostridium butyricum),双歧杆菌菌株(Bifidobacterium lactis BB12)灌胃菌量定为0.15mL/10g体重,频率为每日一次。
菌液需提前培养,每周活化保证新鲜,并分别测定浓度。
Ob/ob小鼠购自中国医学科学院北京协和医学院动物研究所,温度20-24摄氏度,恒湿50-60%,光照12小时(8:00-20:00),隔音,自由摄食、饮水,适应环境一周后进行实验。血糖仪为德国罗氏公司产品。
方法:
(1)雄性C57小鼠6-8周,体重30-32,10只,作为正常对照组;雄性ob/ob 小鼠6-8周,体重38-42g,测定空腹血糖,依据血糖值和体重情况平均分组:
(2)模型对照组;
(3)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL;
(4)加式乳杆菌(Lactobacillus gasseri)1×109cfu/mL;
(5)鼠李糖乳杆菌GM-020 1×109cfu/mL;
(6)丁酸梭菌菌株(Clostridium butyricum)1×109cfu/mL;
(7)双歧杆菌菌株(Bifidobacterium lactis BB12)1×109cfu/mL;
(8)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+加式乳杆菌(Lactobacillus gasseri)1×109cfu/mL;
(9)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+加式乳杆菌(Lactobacillus gasseri)2×109cfu/mL;
(10)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+加式乳杆菌(Lactobacillus gasseri)0.5×109cfu/mL;
(11)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+鼠李糖乳杆菌GM-020 1×109cfu/mL;
(12)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+鼠李糖乳杆菌GM-020 2×109cfu/mL;
(13)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+鼠李糖乳杆菌GM-020 0.5×109cfu/mL;
(14)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+丁酸梭菌菌株(Clostridium butyricum)1×109cfu/mL;
(15)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+丁酸梭菌菌株(Clostridium butyricum)2×109cfu/mL;
(16)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+丁酸梭菌菌株(Clostridium butyricum)0.5×109cfu/mL;
(17)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+双歧杆菌菌株(Bifidobacterium lactis BB12)1×109cfu/mL;
(18)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+双歧杆菌菌株(Bifidobacterium lactis BB12)2×109cfu/mL;
(19)解木聚糖拟杆菌(Bacteroides xylanisolvens)1×109cfu/mL+双歧杆菌菌株(Bifidobacterium lactis BB12)0.5×109cfu/mL;
每组8只,连续给药5周。模型对照组给予等量的厌氧PBS。
解木聚糖拟杆菌(Bacteroides xylanisolvens)与益生菌的组合效果:
测定指标:1)对体重和血糖的影响:给菌第7天、14天、21天、28天、 35天称量体重并记录,给药后尾尖取血测血糖值(见表5)。
2)葡萄糖耐量实验(OGTT):给药第25天测葡萄糖耐量:动物禁食12小时取血(0时)给菌,给菌并口服葡萄糖(2.0g/kg),分别30,60,120分钟尾尖取血测血糖值(见表6)。
3)末次给菌后,麻醉处死,取血,4摄氏度3000rpm离心,测定血清总胆固醇TC,低密度脂蛋白LDL-C,甘油三酯TG。
实验结果表明解木聚糖拟杆菌(Bacteroides xylanisolvens)对高血糖小鼠的血糖有显著作用,同时可以控制体重上升,对于糖负荷小鼠也有显著降低作用(表 5和表6)。与加式乳杆菌(Lactobacillus gasseri),GM-020,Bifidobacterium lactis BB12,Clostridium butyricum不同剂量联用后,效果更为显著,可以用于制备治疗II型糖尿病、降血脂、肥胖的药品或与其它益生菌合用治疗II型糖尿病、肥胖、高血脂或在治疗过程中/后起辅助作用。
表5解木聚糖拟杆菌及其益生菌组合物对高血糖小鼠ob/ob血糖与体重的影响
表6木聚糖拟杆菌及其益生菌组合物对高血糖小鼠ob/ob葡萄糖糖耐量的影响
与对照组和模型组比较,菌株及组合物可以显著改善小鼠血脂情况,对小鼠血清ALT也有很好的逆转作用,提示可以保护高血脂造成的肝损伤结果见表 7。
表7木聚糖拟杆菌及其益生菌组合物对高血糖小鼠ob/ob的血脂和肝功能影响
实施例4
拟杆菌对非酒精性脂肪性肝病的影响
材料:被测菌株为解木聚糖拟杆菌(Bacteroides xylanisolvens,简写:BX), 多里氏拟杆菌(Bacteroides dorei,简写:BD),卵形拟杆菌(Bacteroides ovatus,简写:BO),灌胃菌量定为0.15mL/10g体重,菌浓为1×107cfu/mL,浓缩后浓度为1×109cfu/mL,频率为每日一次。菌液需提前培养,每周活化保证新鲜,并分别测定浓度。
雄性SPF级Wister大鼠60只,体重180-220g,购自维通利华实验动物中心。温度20-24摄氏度,恒湿50-60%,光照12小时(8:00-20:00),隔音,自由摄食、饮水,适应环境一周后进行实验。血清总胆固醇TC试剂盒(批号20131112),低密度脂蛋白LDL-C试剂盒(批号20140114),高密度脂蛋白HDL-C试剂盒(批号20140413),甘油三酯TG试剂盒(批号20131226),谷草转氨酶ALT试剂盒 (批号20131006)购自南京建成生物工程研究所。
方法:雄性SPF级Wister大鼠随机分组:(1)正常组;(2)模型对照组; (3)解木聚糖拟杆菌(Bacteroides xylanisolvens),1×109cfu/mL;(4)多里氏拟杆菌(Bacteroidesdorei),1×109cfu/mL;(5)卵形拟杆菌(Bacteroides ovatus), 1×109cfu/Ml。每组10只。正常组大鼠标准饲料喂养,其余组大鼠每天喂食胆碱缺乏饲料(高脂饲料),检测大鼠摄食量及体重。胆碱缺乏饲料喂养会诱发肝脏细胞变性、肝炎及肝损伤,同时血脂水平升高并诱发胰岛素抵抗,是常用的啮齿类动物脂肪肝的造模方法。
高脂饮食喂养8周后,给药组开始给菌,连续给菌4周。正常组和模型对照组给予等量的厌氧PBS。给药四周后,麻醉处死大鼠,取肝组织和血。
测定指标:1)肝脏指数。
2)测定血清总胆固醇、高密度脂蛋白、低密度脂蛋白及甘油三酯含量。
3)测定谷丙转氨酶含量。
4)肝脏组织切片:末次给药后,麻醉处死,冰上取肝脏,并迅速放入福尔马林中固定,准备组织切片。
实验结果,与正常对照组比较,模型组肝指数显著升高,给予解木聚糖拟杆菌(Bacteroides xylanisolvens),后能显著降低非酒精性脂肪性肝病大鼠的肝指数。同时模型组的TC、LDL-C、TG均显著升高,HDL-C显著降低,提示本模型造成明显的血脂紊乱,与模型组相比,给予解木聚糖拟杆菌(Bacteroides xylanisolvens),多里氏拟杆菌(Bacteroidesdorei),卵形拟杆菌(Bacteroides ovatus)后均可降低非酒精性脂肪性肝病大鼠的血脂,同时还能改善肝功能,降低血浆ALT的含量。
表8解木聚糖拟杆菌非酒精性脂肪性肝病的影响
结合解剖时对肝脏大体的肉眼观察和组织病理切片的HE染色发现(图1),模型组大鼠肝细胞内均有大量大小不等的脂肪空泡,形成脂肪肝,同时,天狼猩红染色发现模型组大鼠肝脏纤维化情况明显,红色胶原纤维形成网状结构(图 2)。而解木聚糖拟杆菌(Bacteroides xylanisolvens),多里氏拟杆菌(Bacteroides dorei),卵形拟杆菌(Bacteroides ovatus)中大鼠肝细胞内的脂肪空泡及肝脏纤维化情况基本消失。结果表明解木聚糖拟杆菌(Bacteroides xylanisolvens)、多里氏拟杆菌(Bacteroides dorei),卵形拟杆菌(Bacteroides ovatus)均可以有效防治由于肥胖引起的非酒精性脂肪性肝病。
实施例5
拟杆菌(Bacteroide)通过产生叶酸(维生素B9)改善脂代谢紊乱
材料与方法:
被测菌株为解木聚糖拟杆菌(Bacteroides xylanisolvens,简写:BX),多里氏拟杆菌(Bacteroides dorei,简写:BD),卵形拟杆菌(Bacteroides ovatus,简写:BO),在YCFA培养基中厌氧培养,一组加入30mg/ml底物pABA,另一组不加pABA,菌株体外培养24小时后,取菌液1ml,超声破碎5min,室温离心5000g 5min,取上清液利用叶酸检测Elisa试剂盒(F14536-8,北京华博德亿生物技术有限公司)。同时,取实施例2中ob/ob小鼠血浆,肝脏匀浆液(100mg 肝脏溶于600ul PBS,匀浆),利用叶酸检测Elisa试剂盒(F14536-8,北京华博德亿生物技术有限公司)检测叶酸含量。
结果:加入pABA底物后,BX,BD,BO菌组叶酸含量均显著提高(图3);同时,与模型组相比,BX,BD,BO组血浆,肝脏中叶酸含量均有显著提高,表明BX,BD,BO可以提高循环叶酸含量,进而改善脂肪代谢(表9)。
表9.BX,BD,BO对ob/ob小鼠叶酸含量的影响
应理解,在本发明范围内,本发明的上述各技术特征和在下文(如实施例) 中具体描述的各技术特征之间都可以相互组合,从而构成新的或优选的技术方案。限于篇幅,在此不再一一赘述。
Claims (5)
1.一种拟杆菌在预防和/或治疗代谢性疾病的药品、保健品或食品中的应用。
2.根据权利要求1所述的应用,其特征在于,所述的代谢性疾病包括肥胖、高血糖、高血脂、非酒精性脂肪性肝病。
3.根据权利要求1所述的应用,其特征在于,所述的拟杆菌包括解木聚糖拟杆菌、多里氏拟杆菌、卵形拟杆菌的菌体及其发酵代谢物。
4.一种菌剂在预防和/或治疗代谢性疾病的药品、保健品或食品中的应用,其特征在于,所述的菌剂包括益生菌和解木聚糖拟杆菌及其发酵代谢物;
所述的益生菌包括氏乳杆菌、鼠李糖乳杆菌GM-020、丁酸梭菌、双歧杆菌中任何一种或多种。
5.根据权利要求4所述的应用,其特征在于,所述的代谢性疾病包括肥胖、糖尿病、高血脂、非酒精性脂肪性肝病。
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CN115400153A (zh) * | 2022-09-29 | 2022-11-29 | 北京大学 | 拟杆菌在制备用于预防或治疗尼古丁相关代谢性疾病的产品中的用途、相关产品及培养方法 |
Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101125151A (zh) * | 2006-08-16 | 2008-02-20 | 大连森佰澳科技有限公司 | 类杆菌信号分子微生态制剂及其制备方法 |
CN101827600A (zh) * | 2007-08-17 | 2010-09-08 | 雀巢产品技术援助有限公司 | 通过调节肠道菌的量来预防和/或治疗代谢性疾病 |
CN101903032A (zh) * | 2007-10-26 | 2010-12-01 | 布伦达·E.·穆尔 | 益生菌组合物及用来引起和维持体重减轻的方法 |
CN103865844A (zh) * | 2014-02-18 | 2014-06-18 | 浙江省农业科学院 | 单形拟杆菌l8及在降解琼胶或琼胶寡糖中的应用 |
CN105030842A (zh) * | 2015-08-24 | 2015-11-11 | 上海交通大学医学院附属瑞金医院 | Bacteroides intestinalis DSM 17393菌株的应用 |
CN105106243A (zh) * | 2015-08-03 | 2015-12-02 | 上海交通大学医学院附属瑞金医院 | Bacteroides thetaiotaomicron VPI-5482在制备治疗或预防肥胖症药物中的应用 |
CN106389478A (zh) * | 2015-07-31 | 2017-02-15 | 广州知易生物科技有限公司 | 脆弱拟杆菌在治疗和/或预防肥胖症或糖尿病中的应用 |
CN106852938A (zh) * | 2015-12-09 | 2017-06-16 | 深圳华大基因研究院 | 拟杆菌(Bacteroides)在治疗和预防肥胖相关疾病中的应用 |
CN107002022A (zh) * | 2014-09-30 | 2017-08-01 | 上海交通大学医学院附属瑞金医院 | 拟杆菌在治疗或预防肥胖相关疾病中的用途 |
CN107002023A (zh) * | 2014-09-30 | 2017-08-01 | 上海交通大学医学院附属瑞金医院 | 拟杆菌在治疗或预防肥胖相关疾病中的用途 |
CN107073046A (zh) * | 2014-09-30 | 2017-08-18 | 深圳华大基因科技有限公司 | 拟杆菌属在预防和治疗冠状动脉疾病中的用途 |
CN107206030A (zh) * | 2014-12-08 | 2017-09-26 | 财团法人峨山社会福祉财团 | 包含生酸拟杆菌作为有效成分的用于预防或治疗代谢性疾病的药学组合物 |
CN107208037A (zh) * | 2014-09-30 | 2017-09-26 | 深圳华大基因科技有限公司 | 拟杆菌属在预防和治疗冠状动脉疾病中的用途 |
TWI609959B (zh) * | 2016-12-27 | 2018-01-01 | 財團法人國家實驗研究院 | 減少體重獲得、體脂肪堆積或肝臟中三酸甘油酯累積之屎副擬桿菌及包含其之組成物及其用途 |
CN107550942A (zh) * | 2017-09-08 | 2018-01-09 | 中国科学院微生物研究所 | 副拟杆菌在治疗和预防代谢性疾病中的应用 |
-
2019
- 2019-03-04 CN CN201910160192.5A patent/CN111714522B/zh active Active
Patent Citations (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101125151A (zh) * | 2006-08-16 | 2008-02-20 | 大连森佰澳科技有限公司 | 类杆菌信号分子微生态制剂及其制备方法 |
CN101827600A (zh) * | 2007-08-17 | 2010-09-08 | 雀巢产品技术援助有限公司 | 通过调节肠道菌的量来预防和/或治疗代谢性疾病 |
CN101903032A (zh) * | 2007-10-26 | 2010-12-01 | 布伦达·E.·穆尔 | 益生菌组合物及用来引起和维持体重减轻的方法 |
CN103865844A (zh) * | 2014-02-18 | 2014-06-18 | 浙江省农业科学院 | 单形拟杆菌l8及在降解琼胶或琼胶寡糖中的应用 |
CN107208037A (zh) * | 2014-09-30 | 2017-09-26 | 深圳华大基因科技有限公司 | 拟杆菌属在预防和治疗冠状动脉疾病中的用途 |
CN107002022A (zh) * | 2014-09-30 | 2017-08-01 | 上海交通大学医学院附属瑞金医院 | 拟杆菌在治疗或预防肥胖相关疾病中的用途 |
CN107002023A (zh) * | 2014-09-30 | 2017-08-01 | 上海交通大学医学院附属瑞金医院 | 拟杆菌在治疗或预防肥胖相关疾病中的用途 |
CN107073046A (zh) * | 2014-09-30 | 2017-08-18 | 深圳华大基因科技有限公司 | 拟杆菌属在预防和治疗冠状动脉疾病中的用途 |
CN107002023B (zh) * | 2014-09-30 | 2021-04-20 | 上海交通大学医学院附属瑞金医院 | 拟杆菌在治疗或预防肥胖相关疾病中的用途 |
CN107206030A (zh) * | 2014-12-08 | 2017-09-26 | 财团法人峨山社会福祉财团 | 包含生酸拟杆菌作为有效成分的用于预防或治疗代谢性疾病的药学组合物 |
CN106389478A (zh) * | 2015-07-31 | 2017-02-15 | 广州知易生物科技有限公司 | 脆弱拟杆菌在治疗和/或预防肥胖症或糖尿病中的应用 |
CN105106243A (zh) * | 2015-08-03 | 2015-12-02 | 上海交通大学医学院附属瑞金医院 | Bacteroides thetaiotaomicron VPI-5482在制备治疗或预防肥胖症药物中的应用 |
CN105030842A (zh) * | 2015-08-24 | 2015-11-11 | 上海交通大学医学院附属瑞金医院 | Bacteroides intestinalis DSM 17393菌株的应用 |
CN106852938A (zh) * | 2015-12-09 | 2017-06-16 | 深圳华大基因研究院 | 拟杆菌(Bacteroides)在治疗和预防肥胖相关疾病中的应用 |
TWI609959B (zh) * | 2016-12-27 | 2018-01-01 | 財團法人國家實驗研究院 | 減少體重獲得、體脂肪堆積或肝臟中三酸甘油酯累積之屎副擬桿菌及包含其之組成物及其用途 |
CN107550942A (zh) * | 2017-09-08 | 2018-01-09 | 中国科学院微生物研究所 | 副拟杆菌在治疗和预防代谢性疾病中的应用 |
Non-Patent Citations (12)
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115400153A (zh) * | 2022-09-29 | 2022-11-29 | 北京大学 | 拟杆菌在制备用于预防或治疗尼古丁相关代谢性疾病的产品中的用途、相关产品及培养方法 |
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