Ixodes persulcatus is a predominant hard tick species that transmits a wide range of human and animal pathogens. Since bacterial flora of the tick dwelling in the wild always vary according to their hosts and the environment, it is highly desirable that species-associated microbiomes are fully determined by using next-generation sequencing and based on comparative metagenomics. Here, we examine such metagenomic changes of I. persulcatus starting with samples collected from the wild ticks and followed by the reared animals under pathogen-free laboratory conditions over multiple generations. Based on high-coverage genomic sequences from three experimental groups-wild, reared for a single generation or R1, and reared for eight generations or R8 -we identify the core bacterial flora of I. persulcatus, which contains 70 species that belong to 69 genera of 8 phyla; such a core is from the R8 group, which is reduced from 4625 species belonging to 1153 genera of 29 phyla in the wild group. Our study provides a novel example of tick core bacterial flora acquired based on wild-to-reared comparison, which paves a way for future research on tick metagenomics and tick-borne disease pandemics.