CN108541953A - 一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物 - Google Patents
一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物 Download PDFInfo
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- CN108541953A CN108541953A CN201810364707.9A CN201810364707A CN108541953A CN 108541953 A CN108541953 A CN 108541953A CN 201810364707 A CN201810364707 A CN 201810364707A CN 108541953 A CN108541953 A CN 108541953A
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Abstract
本发明涉及一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，该组合物包括复合蛋白质粉、低聚糖益生元、功能性益生元和复合脂溶性维生素，所述的低聚糖益生元包括短链菊粉、低聚果糖和抗性糊精；所述的复合蛋白质粉包括浓缩乳清蛋白、大豆分离蛋白和胶原多肽；所述的功能性益生元由盐酸二甲双胍、茶多酚、花青素和原花青素中的一种或几种组成；所述复合脂溶性维生素包括维生素A、维生素E、维生素D和维生素K。本发明通过多种益生元的特殊配比，达到定向增殖盲肠和回肠中嗜黏蛋白阿卡曼氏菌，并对肠道内的拟杆菌门/厚壁菌门比例进行调节。
Description
技术领域
本发明涉及一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，属于调节肠道微生物技术领域。
背景技术
人体内寄宿着数万亿的微生物，其数量是人体细胞的10倍以上。这些细菌大部分寄宿在人体的肠道内，通过这些寄宿的各种微生物结构形成了一个相对稳定的肠道微生态环境。研究表明人体的肠道菌群是人体最大的免疫器官，在人体免疫调节中扮演着非常重要的角色，并且对人体的神经系统、内分泌系统有种重要的调节作用。各种疾病都伴随着肠道微生态结构的失衡，通过调整肠道微生态结构，能很好的预防和治疗多种疾病。并且大量研究表明肠道微生态结构的失衡是产生高血糖、高血脂、高血压等内分泌-代谢疾病以及人体肥胖的重要内在因素，肠道微生物介导了多种内分泌疾病的代谢途径。
厚壁菌-拟杆菌-放线菌门为主微生物组合构成了的成年人型菌群结构。人体的肠道微菌群结构直接影响了人体的内分泌系统，微生物结构的异常往往引起人体的代谢疾病，其中尤其与拟杆菌门和厚壁菌门二者间适合的比例有关，同时拟杆菌/厚壁菌门比例也对肠道的消化吸收有影响，通过改善拟杆菌/厚壁菌门比例能调节血糖、血脂与体重。
嗜黏蛋白阿卡曼氏菌Akkermansia muciniphila是人体肠道中一种可降解黏蛋白的细菌，研究表明它与肥胖、糖尿病、炎症和代谢紊乱呈负相关；它发挥益生作用的机制可能是可以调节肠道内黏液厚度和维持肠道屏障完整性，以及其他对内分泌的调节作用；尤其对高血糖、肥胖有很好的调节作用；高血糖、肥胖人群的肠道中Akkermansiamuciniphila的含量不到普通人群的1/100。
目前通过益生元调节肠道菌群结构是主要的改善肠道微生态结构的方法。然而由于多数的肠道益生菌对常见益生元的亲和性相近，因此一种益生元的使用会使大量菌群的数量改变，无法靶向增殖某一种或某一类的益生菌。而且如菊粉、水苏糖、中药提取物等常见益生元能大量增殖乳酸菌，而乳酸菌属于厚壁菌门，常见益生元的使用会使拟杆菌门/厚壁菌门降低，引起快速肥胖，长期使用有引起高血糖、高血脂、高血压等内分泌-代谢疾病的风险。对于嗜黏蛋白阿卡曼氏菌Akkermansia muciniphila，目前处于研究阶段，仅发现部分物质能增殖Akkermansia muciniphila且往往会同时增殖双歧杆菌与乳杆菌，靶向性差。目前多种益生元配合药物成分构成的组合物是定向调节肠道微生态结构是学界的研究热点。
发明内容
本发明的目的在于：针对现有技术的缺陷，提出了一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，通过多种益生元的特殊配比，达到定向增殖盲肠和回肠中嗜黏蛋白阿卡曼氏菌，并对肠道内的拟杆菌门/厚壁菌门比例进行调节。
本发明所采用的技术方案是：一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，该组合物包括复合蛋白质粉、低聚糖益生元、功能性益生元和复合脂溶性维生素；所述的低聚糖益生元包括短链菊粉、低聚果糖和抗性糊精，其中所述短链菊粉、低聚果糖、抗性糊精三者质量比例为1：1：1.43。菊粉包括长链菊粉与短链菊粉两种，其中长链菊粉主要作用在增殖乳酸菌等益生菌，但对Akkermansia muciniphila没有明显的增殖作用，短链菊粉对益生菌没有明显的增殖功能，但能促进肠道粘液的生成，增加肠道粘液的量。
低聚果糖是由1～3个果糖基通过β(2—1)糖苷键与蔗糖中的果糖基结合生成的蔗果三糖、蔗果四糖和蔗果五糖的混合物；是一种人体无法消化吸收，但能被肠道内微生物利用的低聚糖，并且具有降低血脂的功能；低聚果糖能促进双歧杆菌生长繁殖，与其他益生元配比能增加Akkermansia muciniphila的丰度。
抗性糊精由淀粉加工而成，是将焙烤糊精的难消化成分用工业技术提取处理并精炼而成的一种低热量葡聚糖，属于低分子水溶性膳食纤维。抗性糊精能为被肠道内微生物分解利用，提供微生物生长所需的物质。抗性糊精黏度较低，能缓和短链菊粉与抗性糊精较高的粘性，避免益生元粘性过大而产生便秘。短链菊粉和抗性糊精通过特殊配比能诱导人体大肠杆菌K12增殖，从而产生ClpB等特殊蛋白，促进肠道细胞分泌多肽YY和GLP-1，降低人体食欲，而且对人体乳杆菌没有较强的促进作用。
在本发明中，所述复合蛋白质粉包括浓缩乳清蛋白、大豆分离蛋白、胶原多肽，且三者的质量比例为5：12：1。
通过控制蛋白质的含量和比例能确保部分蛋白质不在小肠内吸收，而进入肠道被肠道微生物分解吸收，而成为微生物发酵底物而产生醋酸盐。而剩余两种蛋白质能吸收膨胀，而短链菊粉和低聚果糖黏度大能延缓蛋白质的分解。胶原多肽是胶原蛋白水解后的短肽复合物，小肠能快速吸收短肽，使胶原多肽快速吸收。乳清蛋白吸收速率最快,30-40min内即可吸收完毕，大豆蛋白吸收速度适中,在1小时候才能被吸收，通过一个较长的吸收过程，使一定数量的蛋白质能进入肠道被肠道菌群分解，产生益生元的功效。
在本发明中，所述的功能性益生元由盐酸二甲双胍、茶多酚、花青素、原花青素中一种或几种组成。
盐酸二甲双胍是一种白色粉末，是目前常用的口服降血糖药物。降糖作用主要是增加周围组织糖的无氧酵解，增加糖的利用，这一作用的主要部位在小肠，动物试验证实本品可增加小肠的无氧酵解，使空肠对糖的利用增加20％。盐酸二甲双胍对部分肠道微生物有促进作用，并且其与低聚果糖等益生元配合能增殖Akkermansia muciniphila。
植物类黄酮是一种从植物中提取的黄酮类物质，为三元环化合物。包含各种植物色素，具有一定的抗氧化作用，和保护心血管的作用。类黄酮具有调节肠道菌群结构的作用，并且对Akkermansia muciniphila有一定的促进作用。
在本发明中，所述复合脂溶性维生素包括维生素A、维生素E、维生素D、维生素K 。
脂溶性维生素是人体的必须从外界摄取的营养物质，对人体有多种生理功能，缺乏维生素会导致人体产生相应的缺素症，对人体产生较大的危害。由于本组合物含有较多的益生元类物质，尤其是低聚糖类，能显著降低血脂，从而导致血液中的脂溶性维生素浓度降低，吸收量减少，容易产生缺素症。额外添加维生素A、维生素E、维生素D、维生素K的量，能有助维持血液中脂溶性维生素的浓度，避免缺素症的产生。
采用上述技术方案后，本发明的有益效果为：本发明通过多种益生元的特殊配比，达到定向增殖盲肠和回肠中嗜黏蛋白阿卡曼氏菌（Akkermansia muciniphila），并对肠道内的拟杆菌门/厚壁菌门比例进行调节。
附图说明
图1是本发明中实施例1和2的实验结果对比示意图；
图2是本发明中实施例1和2的另一实验结果对比示意图。
具体实施方式
下面将结合实施例对本发明作进一步的说明。
实施例1
一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，该组合物包括乳清蛋白1g、大豆分离蛋白2.5g、胶原多肽0.2g、盐酸二甲双胍0.07g、短链菊粉1.1g、低聚果糖1.1g、抗性糊精1.57g、复合脂溶性维生素（含维生素A、维生素E、维生素D、维生素K）0.01g。
实施例2
一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，该组合物包括乳清蛋白1g、大豆分离蛋白2.5g、胶原多肽0.2g、原花青素0.1g、花青素0.08g、短链菊粉1.2g、低聚果糖1.2g、抗性糊精1.72g、复合脂溶性维生素（含维生素A、维生素E、维生素D、维生素K）0.01g。
实验一：对拟杆菌门/厚壁菌门的影响
实验动物：4周龄体重 18～22g的雄性小鼠。
实验方法：将小鼠放于温度 23～25℃，湿度40%的环境中饲养，每天光照12小时，自由进食及饮水（实验中小鼠饮水为开水），垫料3天更换一次。每只小鼠每天给药量为20mg，将组合物A（植物性多酚益生元组合物）及组合物B（盐酸二甲双胍益生元组合物）添加于饮水中喂养小鼠。每两周收集一次小鼠粪便，保存于灭菌2 ml EP管中，-20℃储存。荧光定量检测粪便中拟杆菌门、厚壁菌门、双歧杆菌及乳酸杆菌的含量。
实验结果：
如图1所示，益生元组合物喂食二周后粪便菌群：
如图2所示，益生元组合物喂食四周后粪便菌群。
实验二：对肠道 Akkermansia muciniphila 的影响
实验方法：取8周龄小鼠，小鼠自由饮水与采食，以适应环境7d后，进行灌胃试验，在灌胃结束后的第1d处死小鼠，每次每组处死3只，快速收集小鼠的空肠、回肠、盲肠、结肠，放在2mL的冻存管，置于液氮中保存对小鼠各肠道内容物进行提取基因组试验，后实时荧光定量PCR检查样品中Akkermansia muciniphila的分布情况。
实验结果：
表1：小鼠肠道中Akkermansia muciniphila的分布情况
| 分组 | 盲肠 | 结肠 | 空肠 | 回肠 |
| control | - | - | - | - |
| MIX A | 30.253±0.545 | 32.461±0.749 | - | - |
| MIX B | 29.264±0.527 | 32.331±0.422 | - | - |
对于本领域的技术人员而言，任何对本技术方案的同等修改和替代都是在本发明的范围之中。因此，在不脱离本发明的精神和范围下所作的均等变换和修改，都应涵盖在本发明的范围。
Claims (7)
1.一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，其特征在于：该组合物包括复合蛋白质粉、低聚糖益生元、功能性益生元和复合脂溶性维生素。
2.根据权利要求1所述的一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，其特征在于：所述的低聚糖益生元包括短链菊粉、低聚果糖和抗性糊精，其中所述短链菊粉、低聚果糖、抗性糊精三者质量比例为1：1：1.43。
3.根据权利要求2所述的一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，其特征在于：所述的低聚果糖是由1～3个果糖基通过β(2—1)糖苷键与蔗糖中的果糖基结合生成的蔗果三糖、蔗果四糖和蔗果五糖的混合物。
4.根据权利要求2所述的一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，其特征在于：所述的抗性糊精由淀粉加工而成，是将焙烤糊精的难消化成分用工业技术提取处理并精炼而成的一种低热量葡聚糖，属于低分子水溶性膳食纤维。
5.根据权利要求1所述的一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，其特征在于：所述的复合蛋白质粉包括浓缩乳清蛋白、大豆分离蛋白和胶原多肽，且三者质量比例为5：12：1。
6.根据权利要求1所述的一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，其特征在于：所述的功能性益生元由盐酸二甲双胍、茶多酚、花青素和原花青素中的一种或几种组成。
7.根据权利要求1所述的一种具有调节肠道微生物结构并增殖嗜黏蛋白阿卡曼氏菌的组合物，其特征在于：所述复合脂溶性维生素包括维生素A、维生素E、维生素D和维生素K。
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| US11503851B1 (en) | 2021-06-28 | 2022-11-22 | DailyColors Health, Inc. | Compositions and methods to counteract processes associated with inflammation and senescence and to support cellular energy and/or metabolism |
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