Ryu Ji-Hwan, Kim Sung-Hee, Lee Hyo-Young, Bai Jin Young, Nam Young-Do, Bae Jin-Woo, Lee Dong Gun, Shin Seung Chul, Ha Eun-Mi, Lee Won-Jae
Division of Molecular Life Science, Ewha Woman's University and National Creative Research Initiative Center for Symbiosystem, Seoul 120-750, South Korea.
Science. 2008 Feb 8;319(5864):777-82. doi: 10.1126/science.1149357. Epub 2008 Jan 24.
Although commensalism with gut microbiota exists in all metazoans, the host factors that maintain this homeostatic relationship remain largely unknown. We show that the intestinal homeobox gene Caudal regulates the commensal-gut mutualism by repressing nuclear factor kappa B-dependent antimicrobial peptide genes. Inhibition of Caudal expression in flies via RNA interference led to overexpression of antimicrobial peptides, which in turn altered the commensal population within the intestine. In particular, the dominance of one gut microbe, Gluconobacter sp. strain EW707, eventually led to gut cell apoptosis and host mortality. However, restoration of a healthy microbiota community and normal host survival in the Caudal-RNAi flies was achieved by reintroduction of the Caudal gene. These results reveal that a specific genetic deficiency within a host can profoundly influence the gut commensal microbial community and host physiology.
尽管后生动物都存在与肠道微生物群的共生关系，但维持这种稳态关系的宿主因素在很大程度上仍不清楚。我们发现肠道同源盒基因Caudal通过抑制核因子κB依赖性抗菌肽基因来调节共生菌与肠道的共生关系。通过RNA干扰抑制果蝇中Caudal的表达会导致抗菌肽的过度表达，进而改变肠道内的共生菌群。特别是一种肠道微生物——葡萄糖杆菌属EW707菌株的优势地位最终导致肠道细胞凋亡和宿主死亡。然而，通过重新引入Caudal基因，在Caudal-RNAi果蝇中恢复了健康的微生物群落和正常的宿主存活率。这些结果表明，宿主体内特定的基因缺陷会深刻影响肠道共生微生物群落和宿主生理机能。
