研究报告

滴丸制剂提升益生菌胃肠存活性的效果分析

  • 李晓晗 ,
  • 林单 ,
  • 刘峰 ,
  • 陈昊鹏 ,
  • 张赛轩 ,
  • 谢智勇 ,
  • 马俊
展开
  • 1(中山大学 药学院(深圳),广东 深圳,518107)
    2(深圳万和制药有限公司,广东 深圳,518107)
第一作者:硕士研究生(马俊工程师和谢智勇教授为共同通信作者,E-mail:majun@wanhe-phar.com;xiezhy@mail.sysu.edu.cn)

收稿日期: 2025-09-02

  修回日期: 2025-11-06

  网络出版日期: 2026-07-17

基金资助

国家自然科学基金项目(82574649);广东省肠道微生态制剂企业重点实验室项目(2022B1212020004);重202319253 肠道菌群移植制剂关键技术研发项目(KJZD20230923114203007)

Droplet formulation improves probiotic survival under simulated gastrointestinal conditions

  • LI Xiaohan ,
  • LIN Dan ,
  • LIU Feng ,
  • CHEN Haopeng ,
  • ZHANG Saixuan ,
  • XIE Zhiyong ,
  • MA Jun
Expand
  • 1(School of Pharmaceutical Sciences(Shenzhen), Sun Yat-sen University, Shenzhen 518107, China)
    2(Shenzhen Wanhe Pharmaceutical Co.Ltd., Shenzhen 518107, China)

Received date: 2025-09-02

  Revised date: 2025-11-06

  Online published: 2026-07-17

摘要

益生菌因具有维持肠道微生态平衡和促进机体健康的作用而备受关注,但其口服制剂易受胃酸和胆盐的破坏而严重制约了其应用。该研究通过模拟的胃肠消化体系,系统比较了不同制剂(滴丸、菌粉)及不同菌株组合对益生菌胃肠耐受性的影响,重点评估滴丸包埋技术的保护效应。选取2种不同菌株组合的滴丸制剂(产品A、C)及其对应菌粉制剂(产品B、D),在pH值为1.5~4.0的人工胃液、胆盐质量浓度为0.3~3 g/L的人工小肠液及胃液-小肠液序贯消化条件下,采用平板计数法监测活菌数与存活率。在pH 1.5条件下,滴丸制剂A与C的存活率分别为97.74%和95.67%,显著高于B(60.08%)和D(0%)(P<0.001);在3 g/L胆盐环境中,滴丸制剂A与C在6 h后存活率保持在85%以上,同样优于对应菌粉组(P<0.001)。序贯消化结果显示,产品A在8 h后仍维持88.52%的存活率(P<0.001),结果表明,滴丸剂型能够提高益生菌在胃酸和胆盐条件下的存活率,并呈现一定的缓释特性,多菌株滴丸制剂在消化胁迫下表现出较单菌株制剂更高的存活稳定性。综上,滴丸技术在双歧杆菌类益生菌中显著增强了抗酸抗胆盐能力,多菌株组合进一步提升了整体耐逆性与存活水平,为益生菌靶向递送与功能实现提供了新思路,推动了新型益生菌制剂的开发应用。

本文引用格式

李晓晗 , 林单 , 刘峰 , 陈昊鹏 , 张赛轩 , 谢智勇 , 马俊 . 滴丸制剂提升益生菌胃肠存活性的效果分析[J]. 食品与发酵工业, 2026 , 52(12) : 106 -115 . DOI: 10.13995/j.cnki.11-1802/ts.044381

Abstract

Probiotics are widely recognized for their role in maintaining gut microbial balance and promoting host health.However, their oral efficacy is often limited by susceptibility to gastric acid and bile salts.This study employed a simulated gastrointestinal digestion system to systematically evaluate the tolerance of probiotics in different formulations (droplet formulations versus lyophilized powders) and strain combinations, with a particular focus on the protective effect of droplet encapsulation.Two droplet formulations (Products A and C) containing distinct strain combinations and their corresponding lyophilized powders (Products B and D) were tested under artificial gastric fluid (pH 1.5-4.0), artificial intestinal fluid with bile salts (0.3-3 g/L), and sequential gastric-intestinal digestion.Viable cell counts and survival rates were determined using the plate counting method.Under pH 1.5, droplet formulations A and C exhibited survival rates of 97.74% and 95.67%, significantly higher than Products B (60.08%) and D (0%) (P<0.001).In 3 g/L bile salt conditions, Products A and C maintained survival rates above 85% after 6 h, outperforming the corresponding powder formulations (P<0.001).Sequential digestion analysis showed that Product A retained 88.52% viability after 8 h (P<0.001).These results demonstrated that droplet formulations substantially enhanced probiotic survival under acidic and bile salt stress and provided a sustained-release effect.Multi-strain droplet formulations exhibited greater stability under digestive stress compared with single-strain counterparts.In conclusion, droplet encapsulation significantly improved the acid and bile tolerance of bifidobacterial probiotics, while multi-strain combinations further enhanced overall resilience and viability, offering a promising strategy for targeted delivery and functional optimization of next-generation probiotic formulations.

参考文献

[1] SICILIANO R A, REALE A, MAZZEO M F, et al.Paraprobiotics:A new perspective for functional foods and nutraceuticals[J].Nutrients, 2021, 13(4):1225.
[2] 张和平, 孙志宏.益生菌调节肠道菌群及其代谢发挥功效的研究进展[J].内蒙古农业大学学报(自然科学版), 2022, 43(5):103-108.
ZHANG H P, SUN Z H.A review on the effect of probiotics on regulating gut microbiota and its metabolites[J].Journal of Inner Mongolia Agricultural University (Natural Science Edition), 2022, 43(5):103-108.
[3] JAVANSHIR N, EBRAHIMI V, MAZHARY Z, et al.The antiviral effects and underlying mechanisms of probiotics on viral infections[J].Microbial Pathogenesis, 2025, 200:107377.
[4] TIAN P J, ZOU R Y, WANG L Y, et al.Multi-probiotics ameliorate major depressive disorder and accompanying gastrointestinal syndromes via serotonergic system regulation[J].Journal of Advanced Research, 2023, 45:117-125.
[5] 刘克锋, 赵杰, 何亮伟, 等.酪酸梭菌活菌对防治婴幼儿抗生素相关性腹泻安全性和有效性的Meta分析[J].中国微生态学杂志, 2022, 34(2):168-174.
LIU K F, ZHAO J, HE L W, et al.Safety and efficacy of viable Clostridium butyricum in the prevention and treatment of antibiotic-associated diarrhea in infants and young children:A meta-analysis[J].Chinese Journal of Microecology, 2022, 34(2):168-174.
[6] GOODOORY V C, FORD A C.Antibiotics and probiotics for irritable bowel syndrome[J].Drugs, 2023, 83(8):687-699.
[7] TANG C, KONG L Y, SHAN M Y, et al.Protective and ameliorating effects of probiotics against diet-induced obesity:A review[J].Food Research International, 2021, 147:110490.
[8] 陈卫, 谭惠子, 胡斌, 等.益生菌对消化道胃酸和胆盐胁迫的应激机理[J].中国食品学报, 2010, 10(6):1-6.
CHEN W, TAN H Z, HU B, et al.The mechanism of acid and bile tolerance of probiotics in GI-tract[J].Journal of Chinese Institute of Food Science and Technology, 2010, 10(6):1-6.
[9] GAO H X, MA L, SUN W X, et al.Impact of encapsulation of probiotics in oil-in-water high internal phase emulsions on their thermostability and gastrointestinal survival[J].Food Hydrocolloids, 2022, 126:107478.
[10] MULET-CABERO A I, EGGER L, PORTMANN R, et al.A standardised semi-dynamic in vitro digestion method suitable for food-an international consensus[J].Food & Function, 2020, 11(2):1702-1720.
[11] 王露霏, 王彩云, 李嘉文, 等.双歧杆菌四联活菌体外模拟消化液耐受性的考察[J].中国微生态学杂志, 2023, 35(11):1280-1285;1291.
WANG L F, WANG C Y, LI J W, et al.The tolerance of Bifidobacterium quadruple probiotics to the simulated digestive fluid in vitro[J].Chinese Journal of Microecology, 2023, 35(11):1280-1285.
[12] 李彧媛, 张岩, 刘赫, 等.不同类型益生菌制剂在胃肠道中耐受程度的对比[J].中国微生态学杂志, 2021, 33(12):1374-1378.
LI Y Y, ZHANG Y, LIU H, et al.Comparison of tolerances of several probiotic products in gastrointestinal tract[J].Chinese Journal of Microecology, 2021, 33(12):1374-1378.
[13] 朱荻, 陈莎男, 梅晓宏, 等.提高益生菌耐加工贮藏稳定性和体内存活率的递送系统研究进展[J].食品科学, 2023, 44(21):1-13.
ZHU D, CHEN S N, MEI X H, et al.Advances in the delivery systems for improving the processing stability, storage stability and in vivo survival rate of probiotics[J].Food Science, 2023, 44(21):1-13.
[14] LI W, ZHU Y, YE F, et al.Probiotics in cellulose houses:Enhanced viability and targeted delivery of Lactobacillus plantarum[J].Food Hydrocolloids, 2017, 62:66-72.
[15] 吕培佳, 傅玉颖, 李腾.优化嗜酸乳杆菌JYLA-191抗逆性方法研究[J].中国食品学报, 2024, 24(5):161-170.
LYU P J, FU Y Y, LI T.Study on the method of optimizing the resistance of Lactobacillus acidophilus JYLA-191[J].Journal of Chinese Institute of Food Science and Technology, 2024, 24(5):161-170.
[16] 赵芳, 李艳琴, 李彬春.模拟人体胃肠道环境筛选益生乳杆菌[J].微生物学通报, 2016, 43(6):1396-1403.
ZHAO F, LI Y Q, LI B C.Screening of probiotic Lactobacillus in simulated gastrointestinal environment[J].Microbiology China, 2016, 43(6):1396-1403.
[17] NGUYEN H T, VAN DUONG T, TAYLOR L S.Impact of gastric pH variations on the release of amorphous solid dispersion formulations containing a weakly basic drug and enteric polymers[J].Molecular Pharmaceutics, 2023, 20(3):1681-1695.
[18] CHAI L N, WU H, WANG X J, et al.The mechanism of antimicrobial activity of conjugated bile acids against lactic acid bacilli[J].Microorganisms, 2023, 11(7):1823.
[19] SHIMIZU K, ITO M, KATTO M, et al.Identification of genes essential for bile acid resistance in the probiotic Lacticaseibacillus paracasei strain Shirota[J].Letters in Applied Microbiology, 2023, 76(6):ovad062.
[20] PLAZA-DIAZ J, RUIZ-OJEDA F J, GIL-CAMPOS M, et al.Mechanisms of action of probiotics[J].Advances in Nutrition, 2019, 10:S49-S66.
[21] KIEPŚ J, DEMBCZYŃSKI R.Current trends in the production of probiotic formulations[J].Foods, 2022, 11(15):2330.
[22] HE Q W, HUANG J T, ZHENG T T, et al.Treatment with mixed probiotics induced, enhanced and diversified modulation of the gut microbiome of healthy rats[J].FEMS Microbiology Ecology, 2022, 97(12):fiab151.
[23] JONES B V, BEGLEY M, HILL C, et al.Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome[J].Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(36):13580-13585.
[24] BUSTOS A Y, TARANTO M P, GEREZ C L, et al.Recent advances in the understanding of stress resistance mechanisms in probiotics:Relevance for the design of functional food systems[J].Probiotics and Antimicrobial Proteins, 2025, 17(1):138-158.
[25] ZHOU H L, TAN Y B, MCCLEMENTS D J.Applications of the INFOGEST in vitro digestion model to foods:A review[J].Annual Review of Food Science and Technology, 2023, 14:135-156.
文章导航

/

〈 〉