The population dynamics of the human microbiome have been associated with inflammatory bowel disease, cancer, obesity, autoimmune diseases, and many other human disease states. An emerging paradigm in treatment is the administration of live engineered organisms, also called next-generation probiotics. However, the efficacy of these microbial therapies can be limited by the organism's overall performance in the harsh and nutrient-limited environment of the gut. In this review, we summarize the current state of the art use of bacterial and yeast strains as probiotics, highlight the recent development of genetic tools for engineering new therapeutic functions in these organisms, and report on the latest therapeutic applications of engineered probiotics, including recent clinical trials. We also discuss the supplementation of prebiotics as a method of manipulating the microbiome and improving the overall performance of engineered live biotherapeutics.

中文翻译：

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下一代益生菌：工程活生物治疗


人类微生物群的种群动态与炎症性肠病、癌症、肥胖、自身免疫性疾病和许多其他人类疾病状态有关。一种新兴的治疗模式是活体工程生物体的施用，也称为下一代益生菌。然而，这些微生物疗法的功效可能会受到微生物在恶劣和营养有限的肠道环境中的整体表现的限制。在这篇综述中，我们总结了细菌和酵母菌株作为益生菌的最新应用，重点介绍了用于在这些生物体中设计新治疗功能的遗传工具的最新发展，并报告了工程益生菌的最新治疗应用，包括最近的临床试验。我们还讨论了补充益生元作为操纵微生物组和提高工程活生物治疗药物整体性能的方法。