CN111773252B - 一种高效降低2型糖尿病患者血糖、血脂和体重的益生元组合 - Google Patents
一种高效降低2型糖尿病患者血糖、血脂和体重的益生元组合 Download PDFInfo
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Abstract
本发明涉及功能性食品技术领域，特别涉及一种高效降低2型糖尿病患者血糖、血脂和体重的益生元组合。由乳果糖、阿拉伯糖和植物乳杆菌组成的益生元组合，能够高效地改善2型糖尿病患者的血糖、血脂和体重水平。本发明不仅为阐明肠道微生态调控影响糖尿病治疗效果的作用机制提供了重要的理论依据，同时将益生元组合引入了2型糖尿病的饮食治疗方案，为临床改善2型糖尿病的疗效提供了新途径。
Description
技术领域
本发明涉及功能性食品技术领域，特别涉及一种高效降低2型糖尿病患者血糖、血脂和体重的益生元组合。
背景技术
研究表明，糖尿病发病率的增加不仅仅由于遗传、饮食不当或体力活动减少，肠道菌群可能在其中发挥更为重要的作用。肠道微生物菌群与人类共生，却具有150倍于人体基因，其蕴含的海量遗传信息可能成为糖尿病防治的新靶点。文献报道了肠道菌群与2型糖尿病(T2DM)之间的密切关联：T2DM患者肠道内拟杆菌门与硬壁菌门的比值以及普氏拟杆菌与肠球菌的比值与血糖水平呈正相关，而与体重指数无关。与正常人相比，糖尿病患者粪便中的β-变形菌丰度明显增加。利用肠道基因组测序方法(MGWAS)研究了中国T2DM患者的粪便发现，糖尿病患者的肠道菌群发生了中度紊乱，某些产丁酸盐细菌丰度降低、条件致病菌增加，而具有硫酸盐还原能力及抗氧化功能的细菌增多。根据上述研究结果可以发现，相比于正常人，在T2DM患者体内肠道菌群无论是种类还是丰度均发生了异常变化。究竟是肠道菌群异常引发了糖尿病，还是在糖尿病的发生、发展过程中宿主代谢的紊乱导致肠道菌群的异常，还有待进一步研究来证明。
关于肠道微生态如何参与调节T2DM发生的作用机制，目前的研究主要集中在以下几个方面：(1)肠道菌群调节营养和能量的吸收利用。(2)肠道菌群参与脂肪合成及存储。(3)肠道菌群紊乱引发慢性低度炎性反应。随着肠道菌群和肥胖、T2DM关系的研究不断开展，有研究者提出干预肠道微生态可能是今后糖尿病防治领域的重要手段之一。目前研究较多的为生活方式干预或补充有益菌群来影响肠道微生态，从而改善代谢综合征及T2DM患者的胰岛素抵抗和高血糖水平。
目前2型糖尿病的临床治疗方案主要包括：药物控制血糖水平或胰岛素类药物治疗等；而通过调节肠道微生态平衡达到促进患者治疗效果的研究尚不多见。机体的糖脂代谢与肠道消化吸收功能密切相关，肠道微生物的代谢活动在这个过程中发挥着不可替代的关键作用。发明人的前期研究表明，2型糖尿病患者的血糖、血脂、体重和包含自身免疫在内的身体机能与肠道微生态的平衡具有直接的关联——相比于血糖控制不够理想的患者，那些临床疗效更佳的患者，其肠道内部分有益菌的种类和丰度均有不同程度的富集。由此可见，肠道微生态平衡的改变可以影响2型糖尿病患者的临床疗效。市面上的糖尿病口服液(糖浆、溶液、饮料等)，其主要成分为单一的膳食纤维或膳食纤维衍生物，如阿拉伯糖、乳果糖等。糖尿病患者餐前服用可适当稳定餐后血糖、控制肥胖、治疗便秘。但是，实践表明此类膳食纤维因难于消化吸收，剂量稍有不慎即可导致腹部不适、胃肠胀气、厌食、恶心、呕吐及腹泻等不良反应，严重者甚至影响患者正常的生理机能。因此，如何在稳定血糖水平和血脂水平的同时克服上述膳食纤维在使用中可能导致的负面影响显得极为重要。
发明内容
本发明的目的是在众多的糖尿病辅助治疗口服产品中进行创新改进，克服上面提到的不良副作用而形成的一种新型的益生元组合，不仅具有稳定血糖、血脂和控制体重等现有疗效，还进一步改善了患者使用后可能产生的胀气等一系列副作用。
为实现上述目的，本发明的技术方案为：
一种高效降低2型糖尿病患者血糖、血脂和体重的益生元组合，所述益生元组合由糖类益生元和植物乳杆菌(Lactobacillus plantarum)组成。
优选的，所述糖类益生元由乳果糖和阿拉伯糖组成，二者之间的重量比2:1-1:2。
优选的，所述植物乳杆菌(Lactobacillus plantarum)的保藏编号为CGMCC 8198。
优选的，所述植物乳杆菌(Lactobacillus plantarum)的活菌数为108-1010CFU/g。
优选的，所述降低2型糖尿病患者的体重是针对肥胖患者。
优选的，按益生元组合的总重量计，所述糖类益生元的重量百分比为50-70％，所述植物乳杆菌的重量百分比为30-50％。
优选的，按益生元组合的总重量计，所述糖类益生元的重量百分比为60％，所述植物乳杆菌的重量百分比为40％。
进一步的，本发明还提供了益生元组合在制备适于2型糖尿病患者服用的功能性食品中的用途。
优选的，所述功能性食品能够有效降低2型糖尿病患者的血糖、血脂水平，同时避免体重超标。
进一步的，本发明还提供了一种功能性食品，含有前述的益生元组合；所述功能性食品为粉末、颗粒、片剂或胶囊的形式。
乳果糖，别名4-O-β-D-吡喃半乳糖基-D-果糖，是由半乳糖与果糖组成的二糖，在自然界中并不存在，一般以糖浆状产品出现。乳果糖具有重要的生理及药理功能，广泛用于临床医药，保健品和食品添加剂等多个领域。乳果糖在结肠中被消化道菌丛转化成低分子量有机酸，导致肠道内pH值下降，并通过保留水分，增加粪便体积。上述作用刺激结肠蠕动，保持大便通畅，缓解便秘，同时恢复结肠的生理节律。在肝性脑病(PSE)、肝昏迷和昏迷前期，上述作用促进肠道嗜酸菌(如乳酸杆菌)的生长，抑制蛋白分解菌，使氨转变为离子状态；通过降低接触pH值，发挥渗透效应，并改善细菌氨代谢，从而发挥导泻作用。
L-阿拉伯糖对蔗糖的代谢转化具有阻断作用，使其应用在减肥、控制糖尿病等方面。L-阿拉伯糖在食品和药品方面的使用功能主要有两项，一是能抑制水解双糖的酶，因此抑制因摄入蔗糖(在小肠蔗糖酶的作用下分解成葡萄糖和果糖而被吸收)而导致的血糖升高；简称抑制双糖水解的降糖作用。二是因L-阿拉伯糖对双糖水解酶的抑制作用，使在小肠里没被分解的蔗糖在大肠里被微生物分解产生出大量的有机酸，这种有机酸对肝脏合成脂肪有抑制作用，再加上L-阿拉伯糖在小肠里对吸收蔗糖的抑制作用，从而减少体内新脂肪的产生。
植物乳杆菌具有很多的保健作用，如有一定的免疫调节作用；对致病菌有抑制作用；降低血清胆固醇含量和预防心血管疾病；维持肠道内菌群平衡；促进营养物质吸收；缓解乳糖不耐症和抑制肿瘤细胞的形成等。
与现有技术相比，本发明的有益效果为：
由乳果糖、阿拉伯糖和植物乳杆菌组成的益生元组合，能够高效地改善2型糖尿病患者的血糖、血脂和体重水平。乳果糖是双歧杆菌增殖强力促进因子，在临床上能够降低血氨和血浆内毒素，具有“排毒”功能；同时，乳果糖到达结肠被细菌分解为乳酸，刺激肠道蠕动，起到缓泻作用。阿拉伯糖不仅具有特异性抑制蔗糖酶的作用，从而降低蔗糖水解产物葡萄糖和果糖在肠道的吸收达到降糖的目的；它还是一种高效的益生元，能够调节肠道微生态的稳定与平衡。植物乳杆菌能够降低血清胆固醇含量，具有降血脂的功能；不仅如此，它还能调节机体的免疫功能，抑制致病菌的生长，维持肠道内的菌群平衡。最关键的一点，植物乳杆菌优于其它种类具有降血脂功能的乳酸菌的特性在于，它是一种耐酸、耐碱的厌氧菌，且能够大量定植在肠道内环境中，为其稳定长效地发挥功能提供了保障。
综合三种益生元排毒、降糖和降脂的功能，这种益生元组合能够高效地维持2型糖尿病患者的血糖和血脂稳定在正常范围，并有效地避免患者的体重超标，同时也能消除其它单一种类益生元使用中对机体产生的毒副作用。本发明不仅为阐明肠道微生态调控影响糖尿病治疗效果的作用机制提供了重要的理论依据，同时将益生元组合引入了2型糖尿病的饮食治疗方案，为临床改善2型糖尿病的疗效提供了新途径。
具体实施方式
下面对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。所使用的材料、试剂等，如无特殊说明，为可从商业途径得到的试剂和材料。
实施例1
一种高效降低2型糖尿病患者血糖、血脂和体重的益生元组合，按重量百分比计，所述益生元组合由30％乳果糖、30％阿拉伯糖和40％植物乳杆菌CGMCC 8198组成。
实施例2
一种高效降低2型糖尿病患者血糖、血脂和体重的益生元组合，按重量百分比计，所述益生元组合由20％乳果糖、40％阿拉伯糖和40％植物乳杆菌CGMCC 8198组成。
实施例3
一种高效降低2型糖尿病患者血糖、血脂和体重的益生元组合，按重量百分比计，所述益生元组合由40％乳果糖、20％阿拉伯糖和40％植物乳杆菌CGMCC 8198组成。
实施例4
一种高效降低2型糖尿病患者血糖、血脂和体重的益生元组合，按重量百分比计，所述益生元组合由30％乳果糖、20％阿拉伯糖和50％植物乳杆菌CGMCC 8198组成。
实施例5
一种高效降低2型糖尿病患者血糖、血脂和体重的益生元组合，按重量百分比计，所述益生元组合由30％乳果糖、40％阿拉伯糖和30％植物乳杆菌CGMCC 8198组成。
对比例1
一种益生元组合，按重量百分比计，所述益生元组合由60％乳果糖和40％植物乳杆菌CGMCC 8198组成。
对比例2
一种益生元组合，按重量百分比计，所述益生元组合由60％阿拉伯糖和40％植物乳杆菌CGMCC 8198组成。
对比例3
一种益生元组合，按重量百分比计，所述益生元组合由30％乳果糖、30％阿拉伯糖和40％植物乳杆菌CGMCC 1258组成。
益生元组合对糖尿病小鼠空腹血糖、血脂、体重的影响
准备SPF级雄性昆明种小鼠，适应性饲养7天。随机挑选10只作为空白对照组，其余小鼠采用高脂饲料(配方：10％蛋黄、10％猪油、1％胆同醇、0.2％胆盐、78.8％基料)喂养1个月，禁食过夜后，以低剂量四氧嘧啶(90mg/kg，腹腔注射)继续造模，2天后尾静脉取血测定禁食8h后的血糖值，将血糖值≥11mmol/L的小鼠确定为2型糖尿病造模成功的实验动物。选取造模成功小鼠50只，随机分为模型对照组、实施例1给药组、对比例1-3给药组，每组10只。整个实验过程期间，除空白组饲喂普通饲料外，其余各组皆饲喂高脂饲料。实验时取益生元组合粉末，按剂量相当于10g/kg配制成益生元组合水溶液，每日上午定时按剂量0.2ml/10g灌胃给药。模型对照组与空白对照组同步灌胃给药相同体积的生理盐水。实验过程持续3个月。于给药前、给药4周、给药8周、给药12周分别测定小鼠的空腹血糖(Glu)、总胆固醇(TC)、甘油三酯(TG)和体重(Wt)。实验结果如表1-4所示。
表1.益生元组合对糖尿病小鼠空腹血糖的影响(n＝10，x±s)
表2.益生元组合对糖尿病小鼠总胆固醇的影响(n＝10，x±s)
表3.益生元组合对糖尿病小鼠甘油三酯的影响(n＝10，x±s)
表4.益生元组合对糖尿病小鼠体重的影响(n＝10，x±s)
由表1-4的实验数据可以看出，与模型对照组相比，本发明的益生元组合能够明显改善2型糖尿病小鼠的糖脂代谢，显著降低血糖和血脂水平，同时有效降低小鼠体重。由对比例1-3的实验结果可知，糖类益生元中的乳果糖、阿拉伯糖二者缺一不可，缺少任意一种糖类均会导致疗效减弱，同时植物乳杆菌的具体种类也对疗效具有直接影响。益生元组合—乳果糖、阿拉伯糖和植物乳杆菌通过调节肠道微生态的平衡，促进肠道内益生菌的富集和生长，抑制有害细菌的滞留和积累。益生菌的代谢产物有效调节2型糖尿病小鼠的血糖、血脂和其它代谢指标，保证机体维持正常的代谢和免疫机能，改善临床治疗效果。本发明不仅提供了一种新的益生元组合，通过饮食干预改善2型糖尿病的临床疗效，也为进一步深入认识肠道微生态与机体的代谢功能相互作用的分子机制提供了理论依据。
本领域技术人员不脱离本发明的实质和精神，可以有多种变形方案实现本发明，以上所述仅为本发明较佳可行的实施例而已，并非因此局限本发明的权利范围，凡运用本发明说明书内容所作的等效结构变化，均包含于本发明的权利范围之内。
Claims (5)
1.一种高效降低2型糖尿病患者血糖、血脂和体重的益生元组合，其特征在于，所述益生元组合由糖类益生元和植物乳杆菌(Lactobacillus plantarum)组成；
所述糖类益生元由乳果糖和阿拉伯糖组成，二者之间的重量比2:1-1:2；
所述植物乳杆菌(Lactobacillus plantarum)的保藏编号为CGMCC 8198；
所述糖类益生元的重量百分比为50-70％，所述植物乳杆菌的重量百分比为30-50％。
2.根据权利要求1所述的益生元组合，其特征在于，所述植物乳杆菌(Lactobacillusplantarum)的活菌数为108-1010CFU/g。
3.根据权利要求1所述的益生元组合，其特征在于，所述降低2型糖尿病患者的体重是针对肥胖患者。
4.根据权利要求1所述的益生元组合，其特征在于，按益生元组合的总重量计，所述糖类益生元的重量百分比为60％，所述植物乳杆菌的重量百分比为40％。
5.一种功能性食品，其特征在于，含有如权利要求1-4任一项所述的益生元组合；所述功能性食品为粉末、颗粒、片剂或胶囊的形式。
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