The human oral cavity is a hotspot of numerous, mostly unexplored, viruses that are important for maintaining oral health and microbiome homeostasis. Here, we analyzed 2,792 publicly available oral metagenomes and proposed the Oral Virus Database (OVD) comprising 48,425 nonredundant viral genomes (≥5 kbp). The OVD catalog substantially expanded the known phylogenetic diversity and host specificity of oral viruses, allowing for enhanced delineation of some underrepresented groups such as the predicted Saccharibacteria phages and jumbo viruses. Comparisons of the viral diversity and abundance of different oral cavity habitats suggested strong niche specialization of viromes within individuals. The virome variations in relation to host geography and properties were further uncovered, especially the age-dependent viral compositional signatures in saliva. Overall, the viral genome catalog describes the architecture and variability of the human oral virome, while offering new resources and insights for current and future studies.

The human vagina harbours diverse microorganisms—bacteria, viruses and fungi—with profound implications for women’s health. Genome-level analysis of the vaginal microbiome across multiple kingdoms remains limited. Here we utilize metagenomic sequencing data and fungal cultivation to establish the Vaginal Microbial Genome Collection (VMGC), comprising 33,804 microbial genomes spanning 786 prokaryotic species, 11 fungal species and 4,263 viral operational taxonomic units. Notably, over 25% of prokaryotic species and 85% of viral operational taxonomic units remain uncultured. This collection significantly enriches genomic diversity, especially for prevalent vaginal pathogens such as BVAB1 (an uncultured bacterial vaginosis-associated bacterium) and Amygdalobacter spp. (BVAB2 and related species). Leveraging VMGC, we characterize functional traits of prokaryotes, notably Saccharofermentanales (an underexplored yet prevalent order), along with prokaryotic and eukaryotic viruses, offering insights into their niche adaptation and potential roles in the vagina. VMGC serves as a valuable resource for studying vaginal microbiota and its impact on vaginal health.

Background: The gut virome has been implicated in inflammatory bowel disease (IBD), yet a full understanding of the gut virome in IBD patients, especially across diverse geographic populations, is lacking. Results: In this study, we conducted a comprehensive gut virome-wide association study in a Chinese cohort of 71 IBD patients (15 with Crohn’s disease and 56 with ulcerative colitis) and 77 healthy controls via viral-like particle (VLP) and bulk virome sequencing of their feces. By utilizing an integrated gut virus catalog tailored to the IBD virome, we revealed fundamental alterations in the gut virome in IBD patients. These characterized 139 differentially abundant viral signatures, including elevated phages predicted to infect Escherichia, Klebsiella, Enterococcus_B, Streptococcus, and Veillonella species, as well as IBD-depleted phages targeting Prevotella, Ruminococcus_E, Bifidobacterium, and Blautia species. Remarkably, these viral signatures demonstrated high consistency across diverse populations such as those in Europe and the USA, emphasizing their significance and broad relevance in the disease context. Furthermore, fecal virome transplantation experiments verified that the colonization of these IBD-characterized viruses can modulate experimental colitis in mouse models. Conclusions: Building upon these insights into the IBD gut virome, we identified potential biomarkers for prognosis and therapy in IBD patients, laying the foundation for further exploration of viromes in related conditions.

The gut microbiome of OA patients was completely altered compared to that in healthy individuals, including 279 differentially abundant bacterial species, 10 fungal species and 627 viral operational taxonomic units (vOTUs). Functional analysis of the gut bacteriome and virome also revealed their functional signatures in relation to OA.

The gut microbiome has been implicated in various human diseases, though findings across studies have shown considerable variability. In this study, we reanalyzed 6314 publicly available fecal metagenomes from 36 case-control studies on different diseases to investigate microbial diversity and disease-shared signatures. Using a unified analysis pipeline, we observed reduced microbial diversity in many diseases, while some exhibited increased diversity. Significant alterations in microbial communities were detected across most diseases. A meta-analysis identified 277 disease-associated gut species, including numerous opportunistic pathogens enriched in patients and a depletion of beneficial microbes. A random forest classifier based on these signatures achieved high accuracy in distinguishing diseased individuals from controls (AUC = 0.776) and high-risk patients from controls (AUC = 0.825), and it also performed well in external cohorts. These results offer insights into the gut microbiome’s role in common diseases in the Chinese population and will guide personalized disease management strategies.

Early dysbiosis in the gut microbiota may contribute to the severity of acute pancreatitis (AP), however, a comprehensive understanding of the gut microbiome, potential pathobionts, and host metabolome in individuals with AP remains elusive. Hence, we employed fecal whole-metagenome shotgun sequencing in 82 AP patients and 115 matched healthy controls, complemented by untargeted serum metabolome and lipidome profiling in a subset of participants. Analyses of the gut microbiome in AP patients revealed reduced diversity, disrupted microbial functions, and altered abundance of 77 species, influenced by both etiology and severity. AP-enriched species, mostly potential pathobionts, correlated positively with host liver function and serum lipid indicators. Conversely, many AP-depleted species were short-chain fatty acid producers. Gut microflora changes were accompanied by shifts in the serum metabolome and lipidome. Specifically, certain gut species, like enriched Bilophila wadsworthia and depleted Bifidobacterium spp., appeared to contribute to elevated triglyceride levels in biliary or hyperlipidemic AP patients. Through culturing and whole-genome sequencing of bacterial isolates, we identified virulence factors and clinically relevant antibiotic resistance in patient-derived strains, suggesting a predisposition to opportunistic infections. Finally, our study demonstrated that gavage of specific pathobionts could exacerbate pancreatitis in a caerulein-treated mouse model. In conclusion, our comprehensive analysis sheds light on the gut microbiome and serum metabolome in AP, elucidating the role of pathobionts in disease progression. These insights offer valuable perspectives for etiologic diagnosis, prevention, and intervention in AP and related conditions.