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新型果胶-羧甲基纤维素双层黏蛋白/壳聚糖微复合材料通过模拟胃肠道转运成功保护了下一代益生菌阿克曼氏菌黏液亚种,并改变了结肠体外生物反应器中的微生物群落。

Novel pectin-carboxymethylcellulose-based double-layered mucin/chitosan microcomposites successfully protect the next-generation probiotic Akkermansia muciniphila through simulated gastrointestinal transit and alter microbial communities within colonic ex vivo bioreactors.

机构信息

Department of Biomedical Sciences, School of Infection, Inflammation, and Immunology, College of Medicine and Health, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Department of Biomedical Sciences, School of Infection, Inflammation, and Immunology, College of Medicine and Health, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

出版信息

Int J Pharm. 2024 Nov 15;665:124670. doi: 10.1016/j.ijpharm.2024.124670. Epub 2024 Sep 5.

Abstract

The rapid acceleration of microbiome research has identified many potential Next Generation Probiotics (NGPs). Conventional formulation processing methods are non-compatible, leading to reduced viability and unconfirmed incorporation into intestinal microbial communities; consequently, demand for more bespoke formulation strategies of such NGPs is apparent. In this study, Akkermansia muciniphila (A.muciniphila) as a candidate NGP was investigated for its growth and metabolism properties, based on which a novel microcomposite-based oral formulation was formed. Initially, a chitosan-based microcomposite was coated with mucin to establish a surface culture of A.muciniphila. This was followed by 'double encapsulation' with pectin (PEC) using a novel Entrapment Deposition by Prilling method to create core-shell double-encapsulated microcapsules. The formulation of A.muciniphila was verified to require no oxygen-restriction properties, and additionally, biopolymers were selected, including carboxymethylcellulose (CMC), that support and enhance its growth; consequently, a high viability (6 log CFU/g) of A.muciniphila microencapsulated in PEC-CMC double-encapsulates was obtained. Subsequently, the high stability of the PEC-CMC double-encapsulates was verified in simulated gastric fluid, successfully protecting and then releasing the A.muciniphila under intestinal conditions. Finally, employing a model of gastrointestinal transit and faecal-inoculated colonic bioreactors, significant alterations in microbial communities following administration and successful establishment of A.muciniphila were demonstrated.

摘要

微生物组研究的快速发展已经确定了许多有潜力的下一代益生菌(NGP)。传统的配方加工方法不兼容,导致活菌数减少,无法确认其是否能融入肠道微生物群落;因此,显然需要针对这些 NGP 开发更具针对性的配方策略。在这项研究中,我们研究了黏蛋白阿克曼氏菌(A.muciniphila)作为候选 NGP,基于其生长和代谢特性,开发了一种新型基于微复合材料的口服制剂。首先,用壳聚糖基微复合材料包裹黏蛋白,在其表面培养 A.muciniphila。然后,采用一种新型的“包埋沉积造粒”方法,用果胶(PEC)进行“双重包封”,形成核壳双层包封微胶囊。研究结果表明,A.muciniphila 的配方不需要限制氧气,并且选择了生物聚合物,包括羧甲基纤维素(CMC),以支持和促进其生长;因此,我们获得了具有高活菌数(6 log CFU/g)的 PEC-CMC 双层包封 A.muciniphila 微胶囊。随后,在模拟胃液中验证了 PEC-CMC 双层包封的高稳定性,成功地在肠道条件下保护并释放 A.muciniphila。最后,通过胃肠道转运模型和粪便接种结肠生物反应器,证明了在给予 A.muciniphila 后微生物群落发生了显著变化,并成功建立了 A.muciniphila。

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