Ishizaka Aya, Tamura Azumi, Koga Michiko, Mizutani Taketoshi, Yamayoshi Seiya, Iwatsuki-Horimoto Kiyoko, Yasuhara Atsuhiro, Yamamoto Shinya, Nagai Hiroyuki, Adachi Eisuke, Suzuki Yutaka, Kawaoka Yoshihiro, Yotsuyanagi Hiroshi
Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
Center for Emergency Preparedness and Response, National Institute of Infectious Diseases, Tokyo, Japan.
Microbiol Spectr. 2025 Jan 7;13(1):e0099824. doi: 10.1128/spectrum.00998-24. Epub 2024 Dec 10.
This study compared intestinal DNA phage dynamics and gut microbiota changes observed at the onset of coronavirus disease 2019 (COVID-19). The study participants included 19 healthy individuals and 19 patients with severe acute respiratory syndrome coronavirus 2 infection. Significant differences were observed in the diversity of the intestinal DNA virome after the onset of COVID-19 compared with that in healthy individuals. Classification by their tail morphology resulted in the order Caudovirales, a double-stranded DNA phage, accounting for >95% of all participants. In classifying phages based on host bacteria, a decreased number of phages infecting mainly the Clostridia class was observed immediately after the onset of COVID-19 and recovered over time. After the onset of COVID-19, two distinct movement patterns of intestinal phages and their host bacteria were observed: phage- and bacteria-predominant. The abundance of obligate anaerobes, such as , , and , and the phages hosting these bacteria decreased immediately after the onset of COVID-19, and faster phage recovery was observed compared with bacterial recovery. In contrast, the genus , a facultative anaerobic bacterium, increased immediately after the onset of COVID-19, whereas the phages infecting decreased. Furthermore, immediately after the onset of COVID-19, the percentage of lytic phages increased, whereas that of temperate phages decreased. These observations suggest that the gut microbiota dysbiosis observed immediately after the onset of COVID-19 may be linked to phage dynamics that control gut microbiota and may also affect the recovery from dysbiosis.IMPORTANCEBacteriophages infect and replicate with bacteria and archaea and are closely associated with intestinal bacteria. The symbiotic relationship between gut microbiota and bacteriophages is of interest, but it is challenging to study their dynamics in the human body over time. SARS-CoV-2 infection has been reported to alter the gut microbiota, which is involved in gut immune regulation and pathophysiology, although changes in the intestinal phages of patients with SARS-CoV-2 and their dynamic relationship with the gut microbiota remain unclear. SARS-CoV-2 infection, which follows a transient pathological course from disease onset to cure, may provide a reliable model to investigate these interactions in the gut environment. Therefore, this study aimed to elucidate the correlation between gut microbiota and intestinal DNA virome dynamics in COVID-19 pathogenesis. This study found that the dysbiosis observed in SARS-CoV-2 infection involves a growth strategy that depends on the phage or bacterial dominance.
本研究比较了2019冠状病毒病（COVID-19）发病时观察到的肠道DNA噬菌体动态变化和肠道微生物群变化。研究参与者包括19名健康个体和19名严重急性呼吸综合征冠状病毒2感染患者。与健康个体相比，COVID-19发病后肠道DNA病毒组的多样性存在显著差异。根据其尾部形态分类，双链DNA噬菌体有尾噬菌体目占所有参与者的比例超过95%。在根据宿主细菌对噬菌体进行分类时，观察到在COVID-19发病后立即感染主要梭菌纲的噬菌体数量减少，并随时间恢复。COVID-19发病后，观察到肠道噬菌体及其宿主细菌有两种不同的动态模式：以噬菌体为主和以细菌为主。一些专性厌氧菌，如[具体厌氧菌名称1]、[具体厌氧菌名称2]和[具体厌氧菌名称3]，以及寄生这些细菌的噬菌体在COVID-19发病后立即减少，并且观察到噬菌体的恢复比细菌的恢复更快。相比之下，兼性厌氧菌[具体菌属名称]在COVID-19发病后立即增加，而感染该菌属的噬菌体减少。此外，在COVID-19发病后立即，裂解性噬菌体的比例增加，而温和噬菌体的比例减少。这些观察结果表明，COVID-19发病后立即观察到的肠道微生物群失调可能与控制肠道微生物群的噬菌体动态有关，也可能影响失调的恢复。重要性噬菌体感染细菌和古菌并与之复制，与肠道细菌密切相关。肠道微生物群与噬菌体之间的共生关系备受关注，但研究它们在人体中的随时间动态变化具有挑战性。据报道，严重急性呼吸综合征冠状病毒2感染会改变参与肠道免疫调节和病理生理学的肠道微生物群，尽管严重急性呼吸综合征冠状病毒2感染患者肠道噬菌体的变化及其与肠道微生物群的动态关系仍不清楚。从发病到治愈遵循短暂病理过程的严重急性呼吸综合征冠状病毒2感染可能为研究肠道环境中的这些相互作用提供一个可靠模型。因此，本研究旨在阐明COVID-19发病机制中肠道微生物群与肠道DNA病毒组动态之间的相关性。本研究发现，严重急性呼吸综合征冠状病毒2感染中观察到的失调涉及一种取决于噬菌体或细菌优势的生长策略。
