Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.
Department of Food Science, University of Copenhagen, Copenhagen, Denmark.
Nat Med. 2024 Jan;30(1):138-148. doi: 10.1038/s41591-023-02685-x. Epub 2023 Dec 15.
Bacteriophage (also known as phage) communities that inhabit the gut have a major effect on the structure and functioning of bacterial populations, but their roles and association with health and disease in early life remain unknown. Here, we analyze the gut virome of 647 children aged 1 year from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother-child cohort, all deeply phenotyped from birth and with longitudinally assessed asthma diagnoses. Specific temperate gut phage taxa were found to be associated with later development of asthma. In particular, the joint abundances of 19 caudoviral families were found to significantly contribute to this association. Combining the asthma-associated virome and bacteriome signatures had additive effects on asthma risk, implying an independent virome-asthma association. Moreover, the virome-associated asthma risk was modulated by the host TLR9 rs187084 gene variant, suggesting a direct interaction between phages and the host immune system. Further studies will elucidate whether phages, alongside bacteria and host genetics, can be used as preclinical biomarkers for asthma.
肠道中栖息的噬菌体（也称为噬菌体）群落对细菌种群的结构和功能有重大影响，但它们在生命早期的作用及其与健康和疾病的关联仍不清楚。在这里，我们分析了来自哥本哈根儿童哮喘前瞻性研究（COPSAC）母婴队列的 647 名 1 岁儿童的肠道病毒组，这些儿童从出生起就进行了深度表型分析，并进行了纵向评估哮喘诊断。特定的温和噬菌体类群与后期哮喘的发展有关。特别是，19 个尾噬菌体科的联合丰度被发现对这种关联有显著贡献。将与哮喘相关的病毒组和细菌组特征结合起来，可以对哮喘风险产生累加效应，这意味着病毒组与哮喘之间存在独立的关联。此外，宿主 TLR9 rs187084 基因变异调节了与病毒组相关的哮喘风险，表明噬菌体与宿主免疫系统之间存在直接相互作用。进一步的研究将阐明噬菌体是否与细菌和宿主遗传因素一起，可以作为哮喘的临床前生物标志物。
