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DNA methylation is essential for the survival of bacteriophages (phages), yet, we know little about the methylation of their genomes. Here, we analyze the methylomes of 9,665 metagenome-assembled high-quality human gut phages using single-molecule real-time sequencing. We show that gut phages universally use DNA methylations to escape from host defense systems, and reveal factors that correlate with methylation densities, including coding potential, gene function, and phage lifestyle. Strikingly, more than a third of the phages encode their own DNA methyltransferases (MTases). These phages have increased genome methylation densities, and are more abundant and prevalent than those without MTases. Most MTases are closely homologous to gut bacterial ones, and have been likely exchanged during phage-bacterial host interactions. As gut phages can share ~15% of their genes with gut bacteria at 90% protein similarity, a fast evolving, complex phage-bacterium interaction network can be assumed that shapes both phage and host fitness.DNA甲基化对于噬菌体（bacteriophages，简称phages）的存活至关重要，但目前学界对其基因组的甲基化状况仍知之甚少。本研究利用单分子实时测序（single-molecule real-time sequencing）技术，对9665条高质量宏基因组组装的人类肠道噬菌体甲基化组进行了分析。研究结果表明，肠道噬菌体普遍通过DNA甲基化逃逸宿主防御系统，并揭示了与甲基化密度相关的多项影响因素，包括编码潜力、基因功能以及噬菌体生活方式。值得注意的是，超过三分之一的噬菌体编码自身的DNA甲基转移酶（DNA methyltransferases，简称MTases）。携带此类甲基转移酶的噬菌体，其基因组甲基化密度更高，且丰度和流行率均显著高于未编码该酶的噬菌体。绝大多数此类甲基转移酶与肠道细菌的同源性极高，极有可能在噬菌体与宿主细菌的互作过程中发生了交换。鉴于肠道噬菌体与肠道细菌可在蛋白质相似度达90%的情况下共享约15%的基因，因此可以推断存在一个快速演化且结构复杂的噬菌体-细菌互作网络，该网络同时塑造了噬菌体与宿主的适应性。