CN105106245A - Application of Akkermansia muciniphila BAA-835 strain - Google Patents
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- 241000702462 Akkermansia muciniphila Species 0.000 title abstract description 21
- 208000008589 Obesity Diseases 0.000 claims abstract description 38
- 235000020824 obesity Nutrition 0.000 claims abstract description 36
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
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- 239000006041 probiotic Substances 0.000 abstract description 4
- 235000018291 probiotics Nutrition 0.000 abstract description 4
- 241000702460 Akkermansia Species 0.000 abstract description 3
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Abstract
本发明属于益生菌的应用领域,特别涉及Akkermansia?muciniphila?BAA-835菌株在制备治疗或预防肥胖症方面的应用。本发明通过对C57/BL6雄性SPF级小鼠同窝随机分成对照组和灌菌组的对照试验,灌菌组给予Akkermansia?muciniphila?BAA-835菌株悬液灌胃试验,每天一次,试验5周。通过试验,灌菌组的体重和体脂都明显下降,而且Akkermansiamuciniphila?BAA-835菌株对腹股沟皮下脂肪含量和附睾旁脂肪含量的降低效果非常有效,所以,该菌株可用于肥胖症的治疗或预防的应用中。
The invention belongs to the application field of probiotics, in particular to Akkermansia? muciniphila? Application of the BAA-835 bacterial strain in preparing treatment or prevention of obesity. The present invention divides C57/BL6 male SPF mouse littermates into a control group and a bacterium-filled group at random, and the bacterium-filled group is given Akkermansia? muciniphila? BAA-835 strain suspension was administered orally, once a day, for 5 weeks. Through the experiment, the body weight and body fat of the bacteria injection group decreased significantly, and Akkermansiamuciniphila? The BAA-835 strain is very effective in reducing the inguinal subcutaneous fat content and the peri-epididymal fat content, so the bacterial strain can be used in the treatment or prevention of obesity.
Description
技术领域technical field
本发明属于益生菌的应用领域,特别涉及AkkermansiamuciniphilaBAA-835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 Akkermansiamuciniphila BAA-835 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——编码基因是人类自身基因组编码基因的150倍,这种丰富性决定了其可能在肥胖发生中扮演一定角色。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,存在拟杆菌门与厚壁菌门的比例失调;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BacteroidesuniformisCECT77712。该篇文章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, encodes genes 150 times more than the genes encoded by the human own genome. This abundance determines that it may play a role in the occurrence of obesity. Studies have shown that the intestinal flora structure of obese patients is disordered, the diversity of intestinal bacteria decreases, and there is an imbalance in the ratio of Bacteroides and Firmicutes; studies based on mice have found some bacterial types that can reduce body weight, such as Bacteroides uniformis CECT77712. This article adopts 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 are intragastrically administered every day for 4-8 weeks. The body weight growth curve is recorded. After the test, body fat, blood sugar, serum and adipose tissue were collected. The results showed that continuous intragastric administration of the 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类肥胖症疾病的药物。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-like diseases.
发明内容Contents of the invention
本发明的目的是提供AkkermansiamuciniphilaBAA-835菌株在制备治疗或预防肥胖症方面中的应用,涉及治疗或预防肥胖症的药物、药物组合物、食品及饲料等方面的应用。该菌株降低小鼠血糖,改善小鼠的糖代谢。拓宽了AkkermansiamuciniphilaBAA-835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应用领域。The purpose of the present invention is to provide the application of Akkermansiamuciniphila BAA-835 strain in the preparation of treatment or prevention of obesity, which relates to the application of medicines, pharmaceutical compositions, food and feed for treatment or prevention of obesity. The strain reduces blood sugar and improves glucose metabolism in mice. Widen the scope of use of AkkermansiamuciniphilaBAA-835 strains, and develop an effective, new, non-toxic and side effect-free application field for the treatment and prevention of obesity.
本发明涉及AkkermansiamuciniphilaBAA-835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,AkkermansiamuciniphilaBAA-835菌株具有降低小鼠血糖,改善小鼠糖耐量的有益效果,所以,该菌株是肥胖症干预的益生菌,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 Akkermansia muciniphila BAA-835 strain in the preparation of medicines for treating or preventing obesity. Experiments have proved that the Akkermansiamuciniphila BAA-835 strain has the beneficial effects of reducing blood sugar and improving glucose tolerance in mice. 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的药物组合物,其特征在于,包括:AkkermansiamuciniphilaBAA-835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AkkermansiamuciniphilaBAA-8352菌株;A pharmaceutical composition for treating or preventing obesity, characterized by comprising: Akkermansiamuciniphila BAA-835 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 Akkermansia muciniphila BAA-8352 strain;
该治疗或预防肥胖症的药物组合物为液态时,所述药物组合物中包含107-1011cfu/mL的AkkermansiamuciniphilaBAA-835菌株。When the pharmaceutical composition for treating or preventing obesity is in a liquid state, the pharmaceutical composition contains 10 7 -10 11 cfu/mL of Akkermansia muciniphila BAA-835 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AkkermansiamuciniphilaBAA-835菌株以及食品学上可接受的辅料。优选的,所述治疗或预防肥胖症的食品为固态时,所述食品中包含107-1012cfu/g的AkkermansiamuciniphilaBAA-835菌株;A food for treating or preventing obesity is characterized in that it includes Akkermansiamuciniphila BAA-835 strain and food acceptable auxiliary materials. Preferably, when the food for treating or preventing obesity is solid, the food contains 10 7 -10 12 cfu/g of Akkermansia muciniphila BAA-835 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AkkermansiamuciniphilaBAA-835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 Akkermansia muciniphila BAA-835 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AkkermansiamuciniphilaBAA-835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 Akkermansia muciniphila BAA-835 bacterial strain and acceptable auxiliary materials in feed science.
本发明的有益效果为:本发明提供了AkkermansiamuciniphilaBAA-835菌株在制备治疗或预防肥胖症药物中的新用途,通过实验,验证了AkkermansiamuciniphilaBAA-835菌株对体重和体脂控制非常有效,而且灌菌组小组的腹股沟皮下脂肪含量降低了38.4%,灌菌组小组的附睾旁脂肪含量降低了31.7%,说明Akkermansiamuciniphila菌株对腹股沟皮下脂肪含量和附睾旁脂肪含量的降低效果非常有效。所以,AkkermansiamuciniphilaBAA-835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,拓宽了AkkermansiamuciniphilaBAA-835菌株的应用领域。The beneficial effects of the present invention are: the present invention provides a new application of the AkkermansiamuciniphilaBAA-835 strain in the preparation of medicines for the treatment or prevention of obesity. Through experiments, it has been verified that the AkkermansiamuciniphilaBAA-835 strain is very effective in controlling body weight and body fat. The inguinal subcutaneous fat content of the group was reduced by 38.4%, and the para-epididymal fat content of the bacteria-infused group group was reduced by 31.7%, indicating that the Akkermansiamuciniphila strain is very effective in reducing the inguinal subcutaneous fat content and the para-epididymal fat content. Therefore, the Akkermansiamuciniphila BAA-835 strain can be used in medicines, pharmaceutical compositions, food and feed for treating or preventing obesity, which broadens the application field of the Akkermansiamuciniphila BAA-835 strain.
附图说明Description of drawings
图1是小鼠灌菌5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 in mice after 5 weeks of inoculation with bacteria.
图2是小鼠灌菌5周后,体脂占体重百分比对比图。Figure 2 is a comparison chart of the percentage of body fat in the body weight of mice after 5 weeks of bacteria injection.
图3是小鼠灌菌5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 weight of adipose tissue in the percentage of body weight after 5 weeks of bacteria injection in mice.
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:
本实施例中用到的小鼠模型为:选取10周龄C57/BL6雄性SPF级小鼠,均从上海斯莱克动物实验有限公司购买。小鼠5只一笼饲养于隔离包中,自由进水进食,维持昼夜节律。The mouse model used in this example is: select 10-week-old C57/BL6 male SPF mice, all purchased from Shanghai Slack Animal Experiment Co., Ltd. Five mice were housed in a cage in an isolation bag, with free access to water and food, and to maintain a circadian rhythm.
菌株信息:AkkermansiamuciniphilaBAA-835菌株购买自美国ATCC公司,产品名称:AkkermansiaBAA-835。Strain information: Akkermansia muciniphila BAA-835 strain was purchased from ATCC, USA, product name: Akkermansia BAA-835.
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8-10只,对照组给予无菌PBS灌胃,每天一次;灌菌组给予AkkermansiamuciniphilaBAA-835菌株悬液按照2*109cfu/只小鼠,进行灌胃试验,每天一次。试验5周。期间记录小鼠体重增长率,试验结束后检测脂肪含量等脂代谢相关水平。The C57/BL6 male SPF level mice were randomly divided into control group and bacteria-filled group, with 8-10 mice in each group. The control group was given aseptic PBS, once a day; the bacteria-filled group was given AkkermansiamuciniphilaBAA-835 strain suspension according to 2*10 9 cfu/mouse, intragastric administration test, once a day. Test for 5 weeks. During the period, the weight growth rate of the mice was recorded, and the lipid metabolism-related levels such as fat content were detected after the experiment.
体重和体脂情况如下表1的所示。Body weight and body fat are shown in Table 1 below.
表1Table 1
从表中可以看出,对小鼠进行AkkermansiamuciniphilaBAA-835菌株悬液灌胃后,体重及体脂明显比对照组的小鼠增加缓慢,说明AkkermansiamuciniphilaBAA-835菌株对体重和体脂的控制非常有效。具体如图1和图2所示。As can be seen from the table, after intragastric administration of the Akkermansiamuciniphila BAA-835 bacterial strain suspension to the mice, body weight and body fat were significantly slower than those in the control group, indicating that the Akkermansiamuciniphila BAA-835 bacterial strain is very effective in controlling body weight and body fat. Specifically shown in Figure 1 and Figure 2.
对小鼠的腹股沟皮下脂肪含量及附睾旁脂肪含量进行了测试,具备表2所示:The subcutaneous fat content of the groin and the fat content of the epididymis of the mice were tested, and the results are shown in Table 2:
表2Table 2
从表2中可看出,给予小鼠Akkermansiamuciniphila菌株悬液灌胃后,灌菌组小组的腹股沟皮下脂肪含量降低了38.4%,灌菌组小组的附睾旁脂肪含量降低了31.7%,说明Akkermansiamuciniphila菌株对腹股沟皮下脂肪含量和附睾旁脂肪含量的降低效果非常有效。具体如图3所示。As can be seen from Table 2, after intragastric administration of the Akkermansiamuciniphila bacterial strain suspension in mice, the subcutaneous fat content in the groin of the bacteria-infused group group decreased by 38.4%, and the para-epididymal fat content of the bacteria-infused group group decreased by 31.7%, indicating that the Akkermansiamuciniphila strain It is very effective in reducing the subcutaneous fat content of the groin and the fat content of the epididymis. Specifically shown in Figure 3.
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)
- The application of 1.AkkermansiamuciniphilaBAA-835 bacterial strain in preparation treatment or prevention of obesity disease drug.
- 2. the pharmaceutical composition for the treatment of or preventing obesity, is characterized in that, comprising: AkkermansiamuciniphilaBAA-835 bacterial strain and pharmaceutically acceptable adjuvant.
- 3. treatment according to claim 2 or the pharmaceutical composition that prevents obesity, is characterized in that: when this pharmaceutical composition is solid-state, comprise 10 in described pharmaceutical composition 7-10 12the AkkermansiamuciniphilaBAA-835 bacterial strain of cfu/g; When this pharmaceutical composition is liquid, in described pharmaceutical composition, comprise 10 7-10 11the AkkermansiamuciniphilaBAA-835 bacterial strain of cfu/mL.
- 4. treatment according to claim 3 or the pharmaceutical composition that prevents obesity, it is characterized in that, described pharmaceutically acceptable adjuvant is be selected from least one in carrier, excipient, diluent, lubricant, wetting agent, emulsifying agent, suspension stabiliser, antiseptic, sweeting agent and spice.
- 5. the medicine for the treatment of or preventing obesity, is characterized in that, comprise the pharmaceutical composition any one of claim 2-4.
- 6. treatment according to claim 5 or the medicine that prevents obesity, it is characterized in that, described medicine is at least one dosage form in granule, capsule, tablet, powder agent, oral liquid, suspension and Emulsion.
- 7. the food for the treatment of or preventing obesity, is characterized in that, comprise acceptable adjuvant in AkkermansiamuciniphilaBAA-835 bacterial strain and bromatology.
- 8. treatment according to claim 7 or the food that prevents obesity, is characterized in that, when described food is solid-state, comprise 10 in described food 7-10 12the AkkermansiamuciniphilaBAA-835 bacterial strain of cfu/g; When this food is liquid, in described food, comprise 10 7-10 11the AkkermansiamuciniphilaBAA-835 bacterial strain of cfu/mL.
- 9. treatment according to claim 7 or the food that prevents obesity, it is characterized in that, in described bromatology, acceptable adjuvant is be selected from least one in carrier, excipient, diluent, lubricant, wetting agent, emulsifying agent, suspension stabiliser, antiseptic, sweeting agent and spice.
- 10. the feedstuff for the treatment of or preventing obesity, is characterized in that, comprise acceptable adjuvant in AkkermansiamuciniphilaBAA-835 bacterial strain and feedstuff.
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