The Chinese gut virus catalogue reveals gut virome diversity and disease-related viral signatures.

Abstract

Background: The gut viral community has been increasingly recognized for its role in human physiology and health; however, our understanding of its genetic makeup, functional potential, and disease associations remains incomplete.

Methods: In this study, we collected 11,286 bulk or viral metagenomes from fecal samples across large-scale Chinese populations to establish a Chinese Gut Virus Catalogue (cnGVC) using a de novo virus identification approach. We then examined the diversity and compositional patterns of the gut virome in relation to common diseases by analyzing 6311 bulk metagenomes representing 28 disease or unhealthy states.

Results: The cnGVC contains 93,462 nonredundant viral genomes, with over 70% of these being novel viruses not included in existing gut viral databases. This resource enabled us to characterize the functional diversity and specificity of the gut virome. Using cnGVC, we profiled the gut virome in large-scale populations, assessed sex- and age-related variations, and identified 4238 universal viral signatures of diseases. A random forest classifier based on these signatures achieved high accuracy in distinguishing diseased individuals from controls (AUC = 0.698) and high-risk patients from controls (AUC = 0.761), and its predictive ability was also validated in external cohorts.

Conclusions: Our resources and findings significantly expand the current understanding of the human gut virome and provide a comprehensive view of the associations between gut viruses and common diseases. This will pave the way for novel strategies in the treatment and prevention of these diseases.