model to study genetic effects on the microbiota. ZEBRAFISH AND CRISPR/CAS: A MODEL TO ELUCIDATE HOST GENETIC EFFECTS ON THE MICROBIOTA

The interest in understanding and elucidating host-microbiota interactions is ever increasing. The focus of studying such interactions has long been on the well-established effects the microbiota has on its host. In contrast, little focus has been allocated toput on the participation ofpart the host plays in these intricate interactions. Understanding the role of the host in these interactions may well be an essential key to understand the complexity of the relationship between the host and its microbiota. In this study, we utilize a model in which the effects of host genes on the microbiota can be elucidated and how such effects potentially shape the host-associated microbiota. We apply a hologenomic approach by implementing the CRISPR/Cas system in the zebrafish model to combine effects of host genotype with 16S metabarcoding and metabolomics data. We show that a knockout of the gene coding for the rate-limiting enzyme in melanogenesis, Tyrosinase (tyr), results in changes in the intestinal microbiota of zebrafish and differences in the abundance of specific metabolites, providing evidence of the impact of a single host gene on the composition and function of the intestinal microbiota.

学界对解析宿主-菌群互作（host-microbiota interactions）关系的研究兴趣与日俱增。长期以来，此类互作的研究焦点多集中于菌群对宿主的既定调控效应。与之相对，学界对宿主在这类复杂互作中所发挥的参与作用的关注却寥寥无几。解析宿主在这类互作中的角色，或为阐明宿主与其菌群间关系的复杂性提供关键突破口。本研究采用了一套可解析宿主基因对菌群影响、并探究此类效应如何塑造宿主关联菌群的实验模型。我们以斑马鱼（zebrafish）为模型，借助CRISPR/Cas系统应用全宿主组学（hologenomics）策略，将宿主基因型效应与16S宏条形码测序（16S metabarcoding）及代谢组学（metabolomics）数据相结合。研究结果显示，敲除黑素生成过程中的限速酶编码基因——酪氨酸酶（Tyrosinase，tyr）后，斑马鱼肠道菌群结构发生改变，特定代谢物的丰度亦出现差异，这为单个宿主基因对肠道菌群的组成与功能具有调控作用提供了实验证据。