Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
Computational Bio Big Data Open Innovation Lab., National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
Nat Commun. 2022 Sep 6;13(1):5252. doi: 10.1038/s41467-022-32832-w.
Indigenous bacteriophage communities (virome) in the human gut have a huge impact on the structure and function of gut bacterial communities (bacteriome), but virome variation at a population scale is not fully investigated yet. Here, we analyse the gut dsDNA virome in the Japanese 4D cohort of 4198 deeply phenotyped individuals. By assembling metagenomic reads, we discover thousands of high-quality phage genomes including previously uncharacterised phage clades with different bacterial hosts than known major ones. The distribution of host bacteria is a strong determinant for the distribution of phages in the gut, and virome diversity is highly correlated with anti-viral defence mechanisms of the bacteriome, such as CRISPR-Cas and restriction-modification systems. We identify 97 various intrinsic/extrinsic factors that significantly affect the virome structure, including age, sex, lifestyle, and diet, most of which showed consistent associations with both phages and their predicted bacterial hosts. Among the metadata categories, disease and medication have the strongest effects on the virome structure. Overall, these results present a basis to understand the symbiotic communities of bacteria and their viruses in the human gut, which will facilitate the medical and industrial applications of indigenous viruses.
人类肠道中的本土噬菌体群落（病毒组）对肠道细菌群落（细菌组）的结构和功能有巨大影响，但种群规模上的病毒组变异尚未得到充分研究。在这里，我们分析了日本 4D 队列中 4198 名深度表型个体的肠道 dsDNA 病毒组。通过组装宏基因组读取，我们发现了数千种高质量的噬菌体基因组，包括以前未表征的噬菌体类群，它们的宿主细菌与已知的主要噬菌体类群不同。宿主细菌的分布是噬菌体在肠道中分布的一个强有力的决定因素，病毒组多样性与细菌组的抗病毒防御机制高度相关，如 CRISPR-Cas 和限制修饰系统。我们确定了 97 种不同的内在/外在因素，这些因素显著影响病毒组的结构，包括年龄、性别、生活方式和饮食，其中大多数因素与噬菌体及其预测的细菌宿主都有一致的关联。在元数据类别中，疾病和药物对病毒组结构的影响最大。总的来说，这些结果为理解人类肠道中细菌及其病毒的共生群落提供了基础，这将有助于本土病毒在医学和工业上的应用。
