Haihua Ji, Yiqun Wan, Shengjie Li, Dexi Zhou, Fengying Gu, Jiajiu Sun, Xiaochen Yan, Yu Le, Tingtao Chen, Shaoping Nie, Hao Wan
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引用次数: 0
Abstract
Effective, user-friendly, lifestyle-compatible, and economic treatment for type 2 diabetes (T2D) is urgently needed due to its high incidence and health threats. Here, we remolded Lactococcus lactis through genetic engineering to persistently secrete glucagon-like peptide-1 (L. lactis-GLP-1) and subsequent bioorthogonal arming with dopamine (DA)-based "gripper" and β-glucan (GN)-based "shield" (L. lactis-GLP-1-DA@GN) for treatment of T2D mice via oral administration. With protection by GN-based "shield", L. lactis-GLP-1-DA@GN achieved an impressive enhancement of survival by 20666 times compared with bare L. lactis-GLP-1 after experiencing gastrointestinal conditions and DA-based "gripper" was shielded from interaction with the upper digestive tract. Once prebiotic GN was metabolized by gut microbiota into short-chain fatty acids (SCFAs), underlying DA-based "gripper" was exposed to assist intestinal colonization of L. lactis-GLP-1, achieving synergistic treatment effects through secreted GLP-1 and SCFAs. With all advances, oral administration of L. lactis-GLP-1-DA@GN realized effective T2D treatment through improving glucose/lipid homeostasis, repairing major organs' damages, and positively modulating gut microbiota. Moreover, multi-omics analysis revealed that L. lactis-GLP-1-DA@GN also mainly intervened in liver's signaling pathways regarding lipid metabolism and oxidative regulation to advance anti-T2D process. Our strategy marks reconstruction of probiotics by combining chemical and biological tools, broadening the avenue of manipulating probiotics for disease treatments.
期刊介绍：
Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.
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