Biointerfacial self-assembly generates lipid membrane coated bacteria for enhanced oral delivery and treatment

Zhenping Cao,Xinyue Wang,Yan Pang,Shanshan Cheng,Jinyao Liu

doi:10.1038/s41467-019-13727-9

Abstract

The gut microbiota represents a huge community of microorganisms that play essential roles in immune modulation and homeostasis maintenance. Microbiota transplantation is an important approach to prevent and treat disease as it can inhibit pathogen colonization and positively modulate bacterial composition. However, the development of oral bacterial therapeutics has been restricted by low bioavailability and limited retention in the gastrointestinal tract. Here, we report a simple yet highly efficient method to coat gut microbes via biointerfacial supramolecular self-assembly. Coating can be performed within 15 min by simply vortexing with biocompatible lipids. Bacteria coated with an extra self-assembled lipid membrane exhibit significantly improved survival against environmental assaults and almost unchanged viability and bioactivity. We demonstrate their enhanced efficacies in oral delivery and treatment using two murine models of colitis. We suggest that biointerfacial supramolecular self-assembly may provide a unique platform to generate advanced bacterial therapeutics for the treatment of various diseases.

Highlights

The gut microbiota represents a huge community of microorganisms that play essential roles in immune modulation and homeostasis maintenance
The resultant lipid membrane coated bacteria (LCB) exhibit: significantly improved survival against various extreme conditions including strong acids and alkalis, simulated gastric and intestinal fluids, antibiotics, and ethanol, which is attributed to the presence of the self-assembled lipid membrane; almost unchanged viability and bioactivity as the coating lipid membrane can disassemble after targeting disease sites, which leads to unaffected mucosal adhesion, colonization, and proliferation; simple yet highly efficient preparation and the use of Food and Drug Administration (FDA) approved materials that can facilitate their manufacturing scaleup and subsequent translation
We demonstrate that LCB achieve significantly increased efficacies both in prevention and treatment in Salmonella typhimurium (STm) and dextran sulfate sodium (DSS) induced colitis mouse models

Summary

Introduction

The gut microbiota represents a huge community of microorganisms that play essential roles in immune modulation and homeostasis maintenance. The labeled LCB were measured by flow cytometry, exhibiting a dramatic increase in fluorescent intensity over uncoated bacteria, demonstrating the presence of coating membranes (Fig. 1e).

Results

Conclusion