Search

Additional file 1: Supplementary Figure S1. Virome analyses on inoculum and mouse VLPs. Related to Figs. 2 and 5. Supplementary Figure S2. Experimental colitis severity of UC-HMA and healthy-HMA mice given a single dose of healthy or UC VLPs. Related to Fig. 3. Supplementary Figure S3. Viral and bacterial abundance in UC-HMA mice given UC or healthy VLPs. Related to Fig. 4. Supplementary Figure S4. Viral and bacterial abundance in UC-HMA mice given intact or heat-killed UC VLPs. Related to Fig. 4. Supplementary Figure S5. Bacterial activity in HMA mice given UC or healthy VLPs. Related to Fig. 4. Supplementary Figure S6. Bacterial damage in HMA mice given UC or healthy VLPs. Related to Fig. 4. Supplementary Figure S7. Richness of viral scaffolds and viral clusters in UC-HMA mice given healthy or UC VLPs. Related to Fig. 5. Supplementary Figure S8. Jaccard distance to pooled healthy and UC VLP inoculums over time in UC-HMA mice given UC or healthy VLPs. Related to Fig. 5. Supplementary Figure S9. NMDS on Bray-Curtis dissimilarity of viral clusters between UC-HMA mice given UC or healthy VLPs. Related to Fig. 5. Supplementary Figure S10. PCoA on weighted UniFrac distance between UC-HMA mice given UC or healthy VLPs. Related to Fig. 6. Supplementary Figure S11. PCoA on weighted UniFrac distance between UC-HMA mice given UC VLPs or heat-killed UC VLPs. Related to Fig. 6. Supplementary Figure S12. Relative abundance of temperate phages. Related to Fig. 6. Supplementary Figure S13. DSS does not induce UC gut bacterial prophages in vitro. Related to Fig. 6. Supplementary Figure S14. Human microbiota protects mice from experimental colitis. Related to Fig. 7. Supplementary Table S2. PERMANOVA and effect size of weighted UniFrac distances of bacterial communities between UC-HMA mice given a single dose of healthy VLPs or UC VLPs. Related to Fig. 3. Supplementary Table S3. PERMANOVA and effect size of weighted UniFrac distances of bacterial communities between healthy-HMA mice given a single dose of healthy VLPs or UC VLPs at each sampling point. Related to Fig. 3. Supplementary Table S4. PERMANOVA and effect size of weighted UniFrac distances of bacterial communities between UC-HMA mice and healthy-HMA mice at each sampling point. Related to Fig. 3. Supplementary Table S7. PERMANOVA and effect size of Bray-Curtis dissimilarity on viral scaffolds and viral clusters between UC-HMA mice given healthy and UC VLPs. Related to Fig. 5. Supplementary Table S9. Differentially abundant bacterial species during in HMA mice given healthy VLPs, UC VLPs, or PBS. Related to Fig. 6. Supplementary Table S10. Differentially abundant bacterial species in HMA mice given UC VLPs (+/- DSS), or heat-killed UC VLPs. Related to Fig. 6. Supplementary Table S11. PERMANOVA and effect size of weighted UniFrac distance on bacterial communities between UC-HMA mice given healthy VLPs, UC VLPs or PBS at each sampling point. Related to Fig. 5. Supplementary Table S12. PERMANOVA and effect size of weighted UniFrac distance on bacterial communities between UC-HMA mice given healthy VLPs, UC VLPs or PBS at each sampling point. Related to Fig. 5. Supplementary Table S13. PERMANOVA and effect size of weighted UniFrac distance on bacterial communities between UC-HMA mice given UC VLPs (+DSS), UC VLPs (-DSS) or heat-killed UC VLPs (+DSS) at each sampling point. Related to Fig. 5.

The human gut is an extremely active immunological site interfacing with the densest microbial community known to colonize the human body, the gut microbiota. Despite tremendous advances in our comprehension of how the gut microbiota is involved in human health and interacts with the mammalian immune system, most studies are incomplete as they typically do not consider bacteriophages. These bacterial viruses are estimated to be as numerous as their bacterial hosts, with tremendous and mostly uncharacterized genetic diversity. In addition, bacteriophages are not passive members of the gut microbiota, as highlighted by the recent evidence for their active involvement in human health. Yet, how bacteriophages interact with their bacterial hosts and the immune system in the human gut remains poorly described. Here, we aim to fill this gap by providing an overview of bacteriophage communities in the gut during human development, detailing recent findings for their bacterial-mediated effects on the immune response and summarizing the latest evidence for direct interactions between them and the immune system. The dramatic increase in antibiotic-resistant bacterial pathogens has spurred a renewed interest in using bacteriophages for therapy, despite the many unknowns about bacteriophages in the human body. Going forward, more studies encompassing the communities of bacteria, bacteriophages, and the immune system in diverse health and disease settings will provide invaluable insight into this dynamic trio essential for human health.