A universe of human gut-derived bacterial prophages: unveiling the hidden viral players in intestinal microecology

ABSTRACT

Prophages, which are an existing form of temperate phages that integrate into host genomes, have been found extensively present in diverse bacterial species. The human gut microbiome, characterized by its complexity, dynamism, and interconnectivity among multiple species, remains inadequately understood in terms of the global landscape of bacterial prophages. Here, we analyzed 43,942 human gut-derived bacterial genomes (439 species of 12 phyla) and identified 105,613 prophage regions in ~ 92% of them. 16254 complete prophages were distributed in ~ 24% of bacteria, indicating an extremely uneven prophage distribution across various species within the human gut. Among all identified prophages, ~4% possessed cross-genera (2–20 genera) integration capacity, while ~ 17% displayed broad infection host ranges (targeting 2–35 genera). Functional gene annotation revealed that antibiotic-resistance genes and toxin-related genes were detected in ~ 2.5% and ~ 5.8% of all prophages, respectively. Furthermore, through sequence alignments between our obtained prophages and publicly available human gut phageome contigs, we have observed that ~ 72% of non-redundant prophages are previously unreported genomes, and they illuminate ~ 6.5–9.5% of the individual intestinal “viral dark matter”. Our study represents the first comprehensive depiction of human gut-derived prophages, provides a substantial collection of reference sequences for forthcoming human gut phageome-related investigations, and potentially enables better risk assessment of prophage dissemination.

KEYWORDS:

• Prophage
• gut microbiome
• host range
• antibiotic resistome
• virulence factor
• gut phageome

Acknowledgments

We sincerely thank undergraduates Wenjie Qian, Ao Li, Heng Su, Haomin Zhou, Shengnan Xing, Dongzhe Xiao, Yan Du, Dianhao Chong, Kun Huang, and Qiran Xu for their contribution to the data and their enthusiasm. We would like to thank Home for Researchers (www.home-for-researchers.com/) for English language assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors contributions

Zhangming Pei: Conceptualization, Methodology, Software, Formal analysis, Investigation, Resources, Data Curation, Visualization, Writing – Original Draft. Yufei Liu: Visualization, Writing – Review & Editing. Yutao Chen: Investigation, Software. Tong Pan: Investigation, Software. Xihao Sun: Investigation. Hongchao Wang: Supervision. R. Paul Ross: Writing – Review & Editing. Wenwei Lu: Validation, Supervision, Project administration, Funding acquisition. Wei Chen: Project administration, Funding acquisition.

Data availability statement

The specific information and accession numbers of the bacterial genomes used in this study (Data S1), the sequences of all human gut-derived bacterial prophage sequences (Data S2), non-redundant representative prophages (Data S3), and CRISPR-spacers (Data S4) obtained in this study, as well as the analysis process file of human gut phageomes (Data S5) are available at the Zenodo repository under https://doi.org/10.5281/zenodo.10258953. Any additional information required to reanalyze will be made available upon request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2309684

Additional information

Funding

This research was supported by the National Key Research and Development Program of China (no. 2022YFF1100203).