Acquisition, transmission and strain diversity of human gut-colonizing crAss-like phages

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.

Shining Light on Human Gut Bacteriophages

“…This is consistent with the observed persistence and stability of crAss-like phages in metagenomics datasets over time (Guerin et al, 2018;Edwards et al, 2019;. This also supports the stable engraftment of these phages in certain individuals for up to a year following FMT (Draper et al, 2018;Siranosian et al, 2020). More recently, the isolation of two crAss-like phages closely related to crAss001 which infect Bacteroides thetaiotaomicron have been reported, DAC15 and DAC17 (Hryckowian et al, 2020).…”

“…Thus far we know that crAss-like phages are generally absent from the neonate gut but are acquired in infanthood at low abundances, however, the influence of birth mode on the transmission of these phages has been debated (McCann et al, 2018 ; Liang et al, 2020 ; Siranosian et al, 2020 ). It was initially thought that crAss-like phages were absent from the infant gut, however, now it is believed that they can be vertically transferred from mother to infant (Siranosian et al, 2020 ). The early colonization of crAss-like phages and their universal ubiquity is not surprising considering the predominance of Bacteroidetes in the healthy human gut from infancy (Rodríguez et al, 2015 ).…”

“…delivery route has less impact on bacteriophage composition compared to bacterial composition (McCann et al, 2018;Maqsood et al, 2019;Siranosian et al, 2020). Interestingly, one study found that as much as 63% of bacterial communities in the infant gut are inherited from the mother compared to 15% of viruses thus suggesting that vertical transmission has minimal influence on phageome composition (Maqsood et al, 2019).…”

“…Proposed influencing factors include diet, genetics, birth mode, vertical transmission, and environment (Lim et al, 2016 ). The influence of birth mode on infant gut phageome composition is currently debated, however, more recent findings indicate delivery route has less impact on bacteriophage composition compared to bacterial composition (McCann et al, 2018 ; Maqsood et al, 2019 ; Siranosian et al, 2020 ). Interestingly, one study found that as much as 63% of bacterial communities in the infant gut are inherited from the mother compared to 15% of viruses thus suggesting that vertical transmission has minimal influence on phageome composition (Maqsood et al, 2019 ).…”

The gut virome of healthy children during the first year of life is diverse and dynamic

“…CrAssphages have been reported to represent up to 95% of the total viral load in the adult’s gut, and to be present in 73% to 77% of samples analyzed in diverse human populations [60,61]. Recent studies have shown that these viruses can be found as early as one week after birth [62] and it has been suggested that they could be vertically transmitted from mother to child [63]. In our study these phages were detected in 86% of the infants samples, with abundances ranging between 1% and 82% and with up to 96% of abundance in mothers; this frequency of detection was higher than that found in previous studies in infants, where they were detected in up to 53% of the samples [61].…”