Abstract
CrAss-like phages are double-stranded DNA viruses that are prevalent in human gut microbiomes. Here, we analyze gut metagenomic data from mother-infant pairs and patients undergoing fecal microbiota transplantation to evaluate the patterns of acquisition, transmission and strain diversity of crAss-like phages. We find that crAss-like phages are rarely detected at birth but are increasingly prevalent in the infant microbiome after one month of life. We observe nearly identical genomes in 50% of cases where the same crAss-like clade is detected in both the mother and the infant, suggesting vertical transmission. In cases of putative transmission of prototypical crAssphage (p-crAssphage), we find that a subset of strains present in the mother are detected in the infant, and that strain diversity in infants increases with time. Strain diversity in the p-crAssphage population in mothers is generally low, with a median of 50 variable sites in the 97kb genome. Putative tail fiber proteins are enriched for nonsynonymous strain variation compared to other genes, suggesting a potential evolutionary benefit to maintaining strain diversity in specific genes. Finally, we show that p-crAssphage can be acquired through fecal microbiota transplantation. These results enhance our understanding of the acquisition, individual-level strain diversity, and transmission of crAss-like phages, which have emerged as some of the most successful human-associated microbes.
Footnotes
The manuscript has changed significantly since the first submission, with more robust statistical analysis and strain characterization. We now include crAss-like phages in the manuscript. We have discovered issues in the metagenomic sequencing generated in our lab from HCT patients that invalidates the results as previously presented. These are not the result of mishandling; rather, they are the result of barcode swapping, which was initially described in 2017. As such, we have removed the piece about HCT patient transmission of crAssphage.