菌群调控与免疫治疗

刘尽尧 研究员

上海交通大学分子医学研究院，癌基因及相关基因国家重点实验室

时间：2020年1月14日（星期二）15:50

地点：同安二106教室

厦门大学谱学分析与仪器教育部重点实验室

厦门大学化学化工学院

2020年1月10日

报告摘要：

The gut microbiota represents a huge community of microorganisms including archaea, bacteria, fungi, viruses and microeukaryotes that occupy the gastrointestinal tract. Intensive research on the gut microbial community has provided growing evidence that some of the microorganisms play essential roles in immune modulation, the maintenance of homeostasis, and host health. Disorders of the intestinal microbiota are relevant to a variety of diseases, such as diabetes, obesity, hypertensive heart disease, inflammatory bowel disease, and some cancers. Microbiota transplantation, in particular the delivery of probiotic bacteria to the microbiome, is a promising way to prevent and treat disease. The introduced organisms can accumulate at intestinal site, inhibiting pathogen colonization and positively modulating the balance of bacterial composition, thus exerting beneficial effects. Various forms of liquids, pills, enteric coatings, polymer gels, and dry powder have been developed for oral delivery of probiotic bacteria. While these formulations have been successful in improving delivery efficiency, the use of gut microbes as oral therapeutics has been largely restricted by low oral bioavailability and limited intestinal colonization. New strategies are needed to address these limitations for the development of oral bacterial therapeutics. Here, we report a simple yet highly efficient method to generate super gut microbes, a novel set of membrane coated bacteria which can address all these limitations, by wrapping bacteria with an extra protective membrane. We demonstrate that the coated bacteria exhibit: 1) significantly improved survival against various extreme conditions including strong gastric acid and bile salts; 2) almost unaffected viability and bioactivity as the coating can be removed after targeting disease sites, which leads to unaffected mucosal adhesion, colonization, and proliferation; 3) simple yet highly efficient preparation and the use of Food and Drug Administration approved materials that can facilitate their manufacturing scale-up and subsequent translation. We further show that the coated bacteria have almost 3-times higher survival in the mouse stomach and more than 4-times higher bioavailability in the gut compared with uncoated bacteria. The enhanced reservation in the gut maintains for up to 4 days post-administration. We also demonstrate that the significantly increased efficacies both in prevention and treatment in Salmonella typhimurium and dextran sulphate sodium induced colitis mouse models. We propose that super gut microbes coated with an extra protective membrane could provide a unique platform for advanced delivery of bacteria for a myriad of biomedical applications.

报告人简介：

刘尽尧，上海交通大学分子医学研究院/癌基因及相关基因国家重点实验室，研究员，博士生导师。2013年获上海交通大学材料科学与工程博士学位（导师：中国科学院院士颜德岳教授），2013至2018年分别在美国杜克大学生物医学与工程系（导师：美国发明院院士Ashutosh Chilkoti教授）以及麻省理工学院Koch肿瘤研究所（导师：美国科学院、工程院、医学院三院院士Robert Langer教授）从事博士后研究。研究兴趣主要包括肠道菌群与疾病治疗、生物界面与免疫调控、纳米药物与药物递送、肿瘤早期诊断与成像等。目前主持国家自然科学自然面上基金、上海市高峰高原计划等。至今，在Nat. Commun.、Angew. Chem. Int. Ed.、Adv. Mater.、Chem. Soc. Rev.等期刊发表论文30余篇，相关工作被MIT News、Boston Herald、Nature Communications Editors' Highlights等媒体报道。曾获中国新锐科技人物奖、教育部博士学术新人奖、上海市优秀博士论文等。受邀在美国戈登会议（GRC）等做大会报告。