Multi-biome analysis of Cron's disease and ulcerative colitis patients

Gut microbial dysbiosis has been implicated in the pathogenesis of Inflammatory bowel disease. However, comprehensive analyses of the interactions between various components of the gut microbiome, including the bacteriome, virome, and mycobiome, in ulcerative colitis (UC) and Crohn's disease (CD) remain fully understood. Here, we performed shotgun metagenomic sequencing of feces from patients with UC and CD, and healthy controls in the Japanese 4D cohort, and profiled bacterial taxa, gene functions, and antibacterial genes, bacteriophages, and fungi. External metagenomic datasets from the US, Spain, the Netherlands, and China were analyzed to validate our multi-biome findings. Our analysis showed that Enterococcus faecium and Bifidobacterium spp. were enriched in both diseases. Enriched Escherichia coli was particularly characteristic of CD and was significantly linked to numerous antibiotic-resistance genes involved in efflux pumps and adherent-invasive Escherichia coli virulence factors. Changes in the virome were correlated with the shifts in the bacteriome, including the increased abundance of phages encoding pathogenic genes. Saccharomyces paradoxus and Saccharomyces cerevisiae were significantly enriched in UC and CD, respectively. Saccharomyces cerevisiae and Escherichia coli had specific negative associations with SCFA-producing bacteria in CD. Multi-biome signatures and their interactions in UC and CD showed high similarities between Japan and other countries. Since several bacteria, phages, and fungi formed a hub of an intra- or trans-kingdom network with SCFA producers as well as pathobionts in UC and CD, an approach targeting the interaction network may hold therapeutic promise.