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CN105030842A - Application of Bacteroides intestinalis DSM17393 strain - Google Patents

Application of Bacteroides intestinalis DSM17393 strain Download PDF

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CN105030842A
CN105030842A CN201510523018.4A CN201510523018A CN105030842A CN 105030842 A CN105030842 A CN 105030842A CN 201510523018 A CN201510523018 A CN 201510523018A CN 105030842 A CN105030842 A CN 105030842A
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dsm17393
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宁光
洪洁
王卫庆
刘瑞欣
王计秋
赵少倩
刘�文
石娟
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Ruinjin Hospital Affiliated to Shanghai Jiaotong University School of Medicine Co Ltd
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Ruinjin Hospital Affiliated to Shanghai Jiaotong University School of Medicine Co Ltd
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Abstract

本发属于益生菌的应用领域,特别涉及Bacteroides?intestinalis?DSM?17393菌株在制备治疗或预防肥胖症方面的应用。本发明将C57/BL6雄性SPF级小鼠同窝随机分成对照组和灌菌组,给予Bacteroides?intestinalis?DSM?17393菌株悬液灌胃试验,每天一次。然后给予高脂饮食喂养,试验7周。通过实验,验证了该菌株对体重和体脂的控制非常有效,且腹股沟皮下脂肪含量降低了15%,附睾旁脂肪含量降低了20.9%。所述Bacteroides?intestinalis?DSM?17393菌株可以用于治疗或预防肥胖症的药物、药物组合物、食品及饲料中。

The present invention belongs to the field of application of probiotics, in particular to Bacteroides? intestinalis? DSM? Application of the 17393 strain in the preparation of treatment or prevention of obesity. In the present invention, the male littermates of C57/BL6 male SPF mice are randomly divided into a control group and a bacteria-filled group, and given Bacteroides? intestinalis? DSM? The 17393 strain suspension was administered orally, once a day. Then give high-fat diet feeding, test 7 weeks. Through experiments, it has been verified that the strain is very effective in controlling body weight and body fat, and the content of subcutaneous fat in the groin is reduced by 15%, and the content of paraepididymal fat is reduced by 20.9%. The Bacteroides? intestinalis? DSM? The 17393 strain can be used in medicine, pharmaceutical composition, food and feed for treating or preventing obesity.

Description

Bacteroides intestinalis DSM 17393菌株的应用Application of Bacteroides intestinalis DSM 17393 Strain

技术领域technical field

本发明属于益生菌的应用领域,特别涉及BacteroidesintestinalisDSM17393菌株在治疗或预防肥胖症方面的应用。The invention belongs to the application field of probiotics, in particular to the application of Bacteroides intestinalis DSM17393 bacterial strain in treating or preventing obesity.

背景技术Background technique

肥胖作为2型糖尿病、心血管疾病和肿瘤等的发病危险因素,已成为危害全球的社会公共问题,过去十年间,全基因组关联分析发现了100多个人类肥胖易感位点,然而这些位点仅能解释有限的肥胖发病原因。并且,目前肥胖的有效治疗手段还十分有限,之前美国FDA批准的减肥药物大都因副作用大或效果差而退市,急须开发新的减肥手段。而人类的另一个基因组即肠道菌群基因组在肥胖发生中扮演着越来越重要的角色。研究表明肥胖病人肠道菌群结构失调,肠道细菌多样性下降,存在拟杆菌门与后壁菌门的比例失调;基于小鼠体内的研究发现了一些可以降低体重的细菌类型,如Akkermansiamuciniphila1,BacteroidesuniformisCECT77712。该两篇文章均采用小鼠灌胃的给药方式,普通C57BL6小鼠高脂饮食喂养基础上,分别给予无菌生理盐水或细菌悬液,每天灌胃,持续4-8周,记录体重增长曲线,试验结束后检测体脂、血糖、留取血清和脂肪组织。结果表明该两种细菌持续灌胃可抵抗高脂饮食导致的肥胖及体脂增加,降低血糖,改善全身及脂肪组织炎症。这些研究的发现为开发益生菌干预肥胖提供了重要试验依据和技术手段。Obesity, as a risk factor for type 2 diabetes, cardiovascular disease and tumors, has become a global social public problem. In the past decade, genome-wide association analysis has discovered more than 100 human obesity susceptibility loci. However, these loci Can only explain a limited number of causes of obesity. Moreover, the current effective treatment methods for obesity are still very limited. Most of the weight-loss drugs approved by the US FDA have been withdrawn from the market due to large side effects or poor effects. It is urgent to develop new weight-loss methods. Another human genome, the gut microbiota genome, is playing an increasingly important role in the development of obesity. Studies have shown that the intestinal flora structure of obese patients is out of balance, the diversity of intestinal bacteria is decreased, and there is an imbalance in the ratio of Bacteroidetes to Deuterics; based on studies in mice, some bacterial types that can reduce body weight have been found, such as Akkermansiamuciniphila1, Bacteroides uniformis CECT77712. These two articles both adopt the method of intragastric administration in mice. On the basis of ordinary C57BL6 mice fed with a high-fat diet, they are given sterile normal saline or bacterial suspension, and intragastric administration every day for 4-8 weeks, and the weight gain is recorded. After the test, body fat, blood sugar, serum and adipose tissue were collected. The results showed that continuous intragastric administration of the two bacteria can resist obesity and body fat increase caused by high-fat diet, reduce blood sugar, and improve systemic and adipose tissue inflammation. The findings of these studies provide an important experimental basis and technical means for the development of probiotics to intervene in obesity.

因此本领域迫切需要开发一种有效的、新的、无毒副作用的用于治疗和预防肥胖症疾病的药物。Therefore, there is an urgent need in this field to develop an effective, new and non-toxic drug for the treatment and prevention of obesity.

发明内容Contents of the invention

本发明的目的是提供BacteroidesintestinalisDSM17393菌株在制备治疗或预防肥胖症方面的应用,涉及治疗或预防肥胖症的药物、药物组合物、食品及饲料等方面应用,通过实验,该菌株可显著抑制高脂饮食导致的小鼠体重增加,降低体脂含量及皮下脂肪组织重量。拓宽了BacteroidesintestinalisDSM17393菌株的使用范围,开发了一种有效的、新的、无毒副作用的治疗和预防肥胖症的药物、药物组合物、食品及饲料。The purpose of the present invention is to provide the application of the Bacteroides intestinalis DSM17393 strain in the preparation of treatment or prevention of obesity, which relates to the application of drugs, pharmaceutical compositions, food and feed for the treatment or prevention of obesity. Through experiments, the bacterial strain can significantly inhibit the development of high-fat diet The resulting mice gained weight, decreased body fat content and subcutaneous adipose tissue weight. The scope of use of the Bacteroides intestinalis DSM17393 bacterial strain is broadened, and an effective, new, non-toxic and side effect-free medicine, pharmaceutical composition, food and feed for treating and preventing obesity is developed.

本发明涉及BacteroidesintestinalisDSM17393菌株在制备治疗或预防肥胖症药物中的应用。经过实验证明,BacteroidesintestinalisDSM17393菌株可显著抑制具有降低体脂含量及皮下脂肪组织重量的有益效果,所以,该菌株是肥胖干预的益生菌,可以应用在制备治疗或预防肥胖症的药物中。The invention relates to the application of Bacteroides intestinalis DSM17393 strain in the preparation of medicines for treating or preventing obesity. Experiments have proved that the Bacteroides intestinalis DSM17393 strain can significantly inhibit the beneficial effect of reducing body fat content and subcutaneous adipose tissue weight. Therefore, this strain is a probiotic for obesity intervention and can be used in the preparation of drugs for treating or preventing obesity.

一种治疗或预防肥胖症药物组合物,其特征在于,包括:BacteroidesintestinalisDSM17393菌株以及药学上可接受的辅料。优选的,该治疗或预防肥胖症的药物组合物为固态时,所述药物组合物中包含107-1012cfu/g的BacteroidesintestinalisDSM17393菌株;A pharmaceutical composition for treating or preventing obesity, characterized by comprising: Bacteroides intestinalis DSM17393 strain and pharmaceutically acceptable auxiliary materials. Preferably, when the pharmaceutical composition for treating or preventing obesity is solid, the pharmaceutical composition contains 10 7 -10 12 cfu/g of Bacteroides intestinalis DSM17393 strain;

该治疗或预防肥胖症药物组合物为液态时,所述药物组合物中包含107-1012cfu/mL的BacteroidesintestinalisDSM17393菌株。When the pharmaceutical composition for treating or preventing obesity is in a liquid state, the pharmaceutical composition contains 10 7 -10 12 cfu/mL of Bacteroides intestinalis DSM17393 strain.

所述药学上可接受的辅料为选自载体、赋形剂、稀释剂、润滑剂、润湿剂、乳化剂、悬浮液稳定剂、防腐剂、甜味剂以及香料中的至少一种。经过动物实验,该药物组合物可以治疗或预防肥胖症。The pharmaceutically acceptable adjuvant is at least one selected from the group consisting of carriers, excipients, diluents, lubricants, wetting agents, emulsifiers, suspension stabilizers, preservatives, sweeteners and spices. Through animal experiments, the pharmaceutical composition can treat or prevent obesity.

上述药物组合物可以制备成治疗或预防肥胖症的药物。优选的,所述药物为颗粒剂、胶囊、片剂、粉末剂、口服液、混悬液和乳剂中的至少一种制剂形式。The above pharmaceutical composition can be prepared as a medicine for treating or preventing obesity. Preferably, the medicine is in at least one formulation form of granules, capsules, tablets, powders, oral liquids, suspensions and emulsions.

一种治疗或预防肥胖症的食品,其特征在于,包括BacteroidesintestinalisDSM17393菌株以及食品学上可接受的辅料。优选的,所述食品为固态时,所述食品中包含107-1012cfu/g的BacteroidesintestinalisDSM17393菌株;A food for treating or preventing obesity is characterized in that it includes Bacteroides intestinalis DSM17393 strain and food acceptable auxiliary materials. Preferably, when the food is solid, the food contains 10 7 -10 12 cfu/g of the Bacteroides intestinalis DSM17393 strain;

该治疗或预防肥胖症的食品为液态时,所述食品中包含107-1011cfu/mL的BacteroidesintestinalisDSM17393菌株。When the food for treating or preventing obesity is in a liquid state, the food contains 10 7 -10 11 cfu/mL of Bacteroides intestinalis DSM17393 strain.

所述食品学上可接受的辅料为选自载体、赋形剂、稀释剂、润滑剂、润湿剂、乳化剂、悬浮液稳定剂、防腐剂、甜味剂以及香料中的至少一种。The food acceptable auxiliary material is at least one selected from the group consisting of carriers, excipients, diluents, lubricants, wetting agents, emulsifiers, suspension stabilizers, preservatives, sweeteners and spices.

一种治疗或预防肥胖症的饲料,其特征在于,包括BacteroidesintestinalisDSM17393菌株以及饲料学中可接受的辅料。A feed for treating or preventing obesity is characterized in that it includes Bacteroides intestinalis DSM17393 bacterial strain and acceptable auxiliary materials in feed science.

本发明的有益效果为:本发明提供了BacteroidesintestinalisDSM17393菌株在制备治疗或预防肥胖症领域中的新用途,通过实验,验证了BacteroidesintestinalisDSM17393菌株对体重和体脂的控制非常有效,而且腹股沟皮下脂肪含量降低了15%,附睾旁脂肪含量降低了20.9%。所以,BacteroidesintestinalisDSM17393菌株可以用于治疗或预防肥胖症的药物、药物组合物、食品及饲料中。The beneficial effect of the present invention is: the present invention provides the new use of BacteroidesintestinalisDSM17393 bacterial strain in the field of preparation treatment or prevention of obesity, through experiments, it is verified that BacteroidesintestinalisDSM17393 bacterial strain is very effective in controlling body weight and body fat, and the content of subcutaneous fat in the groin is reduced 15%, and the fat content of the epididymis was reduced by 20.9%. Therefore, the Bacteroides intestinalis DSM17393 strain can be used in medicine, pharmaceutical composition, food and feed for treating or preventing obesity.

附图说明Description of drawings

图1是正常饮食小鼠灌菌7周后,体重增长百分比对比图。Figure 1 is a comparison chart of the percentage of body weight growth of mice fed with normal diet for 7 weeks.

图2是高脂饮食小鼠灌菌7周后,体重增长百分比对比图。Figure 2 is a comparison chart of the percentage of body weight gain after 7 weeks of feeding mice with high-fat diet.

图3是高脂饮食小鼠灌菌7周后,脂肪组织重量占体重百分比对比图。Figure 3 is a comparison chart of the percentage of adipose tissue weight in body weight after 7 weeks of feeding mice with high-fat diet.

具体实施方式Detailed ways

下面结合实施例,对本发明作进一步说明:Below in conjunction with embodiment, the present invention will be further described:

本实施例中用到的大鼠模型为:选取10周龄C57/BL6雄性SPF级小鼠,均从上海斯莱克实验动物有限公司购买。小鼠2-3只一笼饲养于隔离包中,自由进水进食,维持昼夜节律。The rat model used in this example is: select 10-week-old C57/BL6 male SPF mice, all purchased from Shanghai Slack Experimental Animal Co., Ltd. 2-3 mice were housed in an isolation bag in a cage, and they had free access to water and food to maintain a circadian rhythm.

菌株信息:BacteroidesintestinalisDSM17393菌株购买自德国DMS公司。Strain information: Bacteroides intestinalis DSM17393 strain was purchased from German DMS company.

实施例1Example 1

将C57/BL6雄性SPF级小鼠同窝随机分成对照组和灌菌组,每组7-10只,对照组给予无菌PBS灌胃,每天一次;灌菌组给予BacteroidesintestinalisDSM17393菌株悬液按照2*108-109cfu/只小鼠,进行灌胃试验,每天一次。然后给予高脂饮食喂养,试验7周。期间记录小鼠体重增长率,试验结束后检测脂肪含量等。The C57/BL6 male SPF level mice were randomly divided into control group and bacteria-instilled group, with 7-10 mice in each group. The control group was given aseptic PBS, once a day; 10 8 -10 9 cfu/mouse, for intragastric administration test, once a day. Then give high-fat diet feeding, test 7 weeks. During the period, the body weight growth rate of the mice was recorded, and the fat content was detected after the experiment.

体重和脂肪组织称重情况如下表1的所示:The body weight and adipose tissue weighing conditions are shown in Table 1 below:

表1Table 1

从表中可知,对小鼠进行BacteroidesintestinalisDSM17393菌株悬液灌胃后,体重及小鼠腹股沟皮下脂肪含量和附睾旁脂肪含量明显比对照组的小鼠增加缓慢,说明BacteroidesintestinalisDSM17393菌株对体重的控制,对降低小鼠腹股沟皮下脂肪含量和附睾旁脂肪含量的效果非常明显。As can be seen from the table, after carrying out intragastric administration of BacteroidesintestinalisDSM17393 bacterial strain suspension to mice, body weight and mouse groin subcutaneous fat content and epididymis fat content are significantly increased slowly than mice in the control group, indicating that Bacteroides intestinalisDSM17393 bacterial strain controls body weight and reduces The effect of subcutaneous fat content in the inguinal region of mice and the content of para-epididymal fat was very pronounced.

以上所述为本发明的较佳实施例而已,但本发明不应该局限于该实施例所公开的内容。所以凡是不脱离本发明所公开的精神下完成的等效或修改,都落入本发明保护的范围。The above description is only a preferred embodiment of the present invention, but the present invention should not be limited to the content disclosed in this embodiment. Therefore, all equivalents or modifications that do not deviate from the spirit disclosed in the present invention fall within the protection scope of the present invention.

Claims (10)

1.BacteroidesintestinalisDSM17393菌株在制备治疗或预防肥胖症药物中的应用。1. Application of the Bacteroides intestinalis DSM17393 strain in the preparation of a medicament for treating or preventing obesity. 2.一种治疗或预防肥胖症的药物组合物,其特征在于,包括:BacteroidesintestinalisDSM17393菌株以及药学上可接受的辅料。2. A pharmaceutical composition for treating or preventing obesity, characterized by comprising: Bacteroides intestinalis DSM17393 bacterial strain and pharmaceutically acceptable auxiliary materials. 3.根据权利要求2所述的治疗或预防肥胖症的药物组合物,其特征在于:该药物组合物为固态时,所述药物组合物中包含107-1012cfu/g的BacteroidesintestinalisDSM17393菌株;该药物组合物为液态时,所述药物组合物中包含107-1011cfu/mL的BacteroidesintestinalisDSM17393菌株。3. The pharmaceutical composition for treating or preventing obesity according to claim 2, characterized in that: when the pharmaceutical composition is solid, the pharmaceutical composition contains 10 7 -10 12 cfu/g of the Bacteroides intestinalis DSM17393 strain; When the pharmaceutical composition is in a liquid state, the pharmaceutical composition contains 10 7 -10 11 cfu/mL of Bacteroides intestinalis DSM17393 strain. 4.根据权利要求3所述的治疗或预防肥胖症的药物组合物,其特征在于,所述药学上可接受的辅料为选自载体、赋形剂、稀释剂、润滑剂、润湿剂、乳化剂、悬浮液稳定剂、防腐剂、甜味剂以及香料中的至少一种。4. The pharmaceutical composition for the treatment or prevention of obesity according to claim 3, wherein the pharmaceutically acceptable adjuvant is selected from carriers, excipients, diluents, lubricants, wetting agents, At least one of an emulsifier, a suspension stabilizer, a preservative, a sweetener, and a fragrance. 5.一种治疗或预防肥胖症的药物,其特征在于,包括权利要求2-4中任一项的药物组合物。5. A medicament for treating or preventing obesity, characterized in that it comprises the pharmaceutical composition according to any one of claims 2-4. 6.根据权利要求5所述的治疗或预防肥胖症的药物,其特征在于,所述药物为颗粒剂、胶囊、片剂、粉末剂、口服液、混悬液和乳剂中的至少一种制剂形式。6. The medicine for treating or preventing obesity according to claim 5, characterized in that, the medicine is at least one preparation in granules, capsules, tablets, powders, oral liquids, suspensions and emulsions form. 7.一种治疗或预防肥胖症的食品,其特征在于,包括BacteroidesintestinalisDSM17393菌株以及食品学上可接受的辅料。7. A food for treating or preventing obesity, characterized in that it includes Bacteroides intestinalis DSM17393 strain and food acceptable auxiliary materials. 8.根据权利要求7所述的治疗或预防肥胖症的食品,其特征在于,所述食品为固态时,所述食品中包含107-1012cfu/g的BacteroidesintestinalisDSM17393菌株;该食品为液态时,所述食品中包含107-1011cfu/mL的BacteroidesintestinalisDSM17393菌株。8. The food for treating or preventing obesity according to claim 7, characterized in that, when the food is solid, the food contains 10 7 -10 12 cfu/g of the Bacteroides intestinalis DSM17393 strain; when the food is liquid , the food contains 10 7 -10 11 cfu/mL of Bacteroides intestinalis DSM17393 strain. 9.根据权利要求7所述的治疗或预防肥胖症的食品,其特征在于,所述食品学上可接受的辅料为选自载体、赋形剂、稀释剂、润滑剂、润湿剂、乳化剂、悬浮液稳定剂、防腐剂、甜味剂以及香料中的至少一种。9. The food for treating or preventing obesity according to claim 7, characterized in that, the food acceptable adjuvant is selected from carrier, excipient, diluent, lubricant, wetting agent, emulsifying At least one of additives, suspension stabilizers, preservatives, sweeteners and spices. 10.一种治疗或预防肥胖症的饲料,其特征在于,包括BacteroidesintestinalisDSM17393菌株以及饲料学中可接受的辅料。10. A feed for treating or preventing obesity, characterized in that it comprises Bacteroides intestinalis DSM17393 strain and feed acceptable auxiliary materials.
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CN111714522A (en) * 2019-03-04 2020-09-29 中国科学院微生物研究所 Bacteroides and application thereof

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