Common bacteriophage appeared only recently in human gut, study says

The paper, from a team of researchers from the University of Oklahoma, Harvard University and others, was published last week in the journal PLOS One. The research looks into the prevalence of the virus CrAssphage sensu stricto​ and its history in the human gut.

Metagenomic sequencing advances made research possible

The authors noted that recent advances in metagenomic sequencing and development of data mining tools now allow researchers to conduct large-scale studies of human gut bacteriophage diversity using shotgun-sequencing data from human fecal samples.  The resulting data showed that crAssphage, a DNA bacteriophage (there are RNA bacteriophages as well), is highly prevalent in most human guts.  The bacteriophage is named for the cross assembly (cr-Ass) software used to discover it in data mining studies.

The virus was named crAssphage sensu stricto ​to distinguish it from a large family of similar gut dwelling viruses that have been discovered recently.  It is highly prevalent, the authors noted, and seems to show up in the guts of infants in industrialized zones as early as one month of age.

“​CrAssphage is prevalent in available gut metagenomic data from the U.S,. comprising up to 90% of viral particle-derived metagenomes and up to 22% of reads in a total fecal community from the U.S. National Institutes of Health’s Human Microbiome Project cohort. Moreover, crAssphage is up to six times more abundant than all other known bacteriophages that could be reconstructed from these publicly available metagenomes,”​ they found.

Global data set includes mother-daughter, twins info

The researchers looked at the data of fecal samples from 3,341 individuals from different societies, including two hunter gather groups, the Hadza of Tanzania and the Matses from the Amazon jungle of Peru.  The fecal sample data was screened using two approaches:  a direct reference approach keyed to crAssphage itself and a de novo​ metagenomic assembly focusing on marker proteins of the virus.

In addition to its geographical and demographical diversity, the data set included longitudinal information on individuals as well as details on mother-daughter pairs and twins.  The resulting robustness of the data set combined with the two pronged analytical approach allowed the researchers to come to a profound and surprising conclusion.  While we think of evolution as something that happens over timescales of at least hundreds if not thousands of generations, the process can be much faster within the virome, and the advent of crAssphage sensu stricto​ in the human gut is something that has happened only recently.

Recent immigrant to human gut

“The geographic distribution of crAssphage is global, but as observed here, the prevalence of crAssphage is lower within samples from more traditional, hunter-gatherer populations such as the Hadza from Tanzania and Matses from Peru. The overall picture from the data presented here is that crAssphage prevalence is associated with an industrialized lifestyle/diet, but with no associations to health, age, sex, or body-size variables. CrAssphage strains from the same individual tend to cluster together phylogenetically. Overall, crAssphage shows limited biogeographic clustering as seen in cases of a recent population expansion event. We estimate that this expansion occurred approximately within the past few hundred years; however, the mechanism behind this expansion remains uncertain,”​  they concluded.

Lead researcher Tanvi Honap, PhD, of the University of Oklahoma, said the research into the human microbiome is still in its infancy.  It’s unclear, for example, which specific bacterial species play host to the virus so it remains to be seen how useful this information will be to probiotics researchers. At the moment the uncertainty about the host organism(s) would argue against using the bacteriophage as any sort of marker, she said, though she added that the fact that is is so common could make it useful in detecting fecal contamination outside of the body.

“Bacteria belonging to ​Bacteroides species have been suggested as the host of crAssphage. However, we do not know how many species of this genus, as well as whether bacteria belonging to other genera, also serve as the host of crAssphage. Further studies are needed to answer these questions,”​ she told NutraIngredients-USA.

Data supports notion that crAssphage did not coevolve with human gut

Recent studies have found that crAss-like phages may have been present in primate guts for millions of years.  But crAssphage sensu stricto​ itself seems to be a recent addition, and the fact that it does not appear to be associated with any disease or metabolic condition lends credence to this conclusion, Honap asserted.

“Given that we did not find crAssphage in individuals leading traditional lifestyles, such as the Hadza and Matses, as well as the fact that Edwards et al​​. show that is not present in ancient human gut metagenomic data, suggest that this particular bacteriophage, crAssphage, spread in humans along with the shift to an industrialized diet. This is supported by the fact that the supposed host genus, ​Bacteroides, is more abundant in industrialized populations,” ​she said.

“Our study, as well as others (for example, Edwards et al. 2019​​, Liang et al. 2016​​), have not found any association between the presence of crAssphage and disease status. Therefore, it does seem that crAssphage is a part of the normal human virome,​” she added.

Source:​ PLOS One
Published: January 15, 2020 https://doi.org/10.1371/journal.pone.0226930​
Biogeographic study of human gut-associated crAssphage suggests impacts from industrialization and recent expansion​
Authors:  Honap TP, et al.