Scientists find 140,000 virus species in the human gut, most of which are unknown

The coronavirus pandemic has fixed the world on viruses like never before in memory, but new evidence reveals that humans don’t even realize the vast extent of viral existence – even when it’s inside us.

A new database project compiled by scientists has identified more than 140,000 viral species that live in the human intestine – a giant catalog that is even more impressive because half of these viruses were previously unknown to science.

If tens of thousands of newly discovered viruses sound like an alarming development, this is completely understandable. But we must not misinterpret what these viruses within us really represent, say the researchers.

“It is important to remember that not all viruses are harmful, but they represent an integral component of the intestinal ecosystem”, explains biochemist Alexandre Almeida, from the Bioinformatics Institute of the European Molecular Biology Laboratory (EMBL-EBI) and the Wellcome Sanger Institute.

“These samples came mainly from healthy individuals who did not share any specific disease.”

The new virus catalog – called the Gut Phage Database (GPD) – has been compiled by analyzing more than 28,000 individual metagenomas – publicly available DNA sequencing records of intestinal microbiome samples collected in 28 countries – along with almost 2,900 genomes from reference of cultured intestinal bacteria.

The results revealed 142,809 viral species that reside in the human intestine, constituting a specific type of virus known as bacteriophage, which infects bacteria, in addition to single-celled organisms called archaea.

In the mysterious environment of the intestinal microbiome – inhabited by a diverse mix of microscopic organisms, encompassing bacteria and viruses – bacteriophages are believed to play an important role in regulating bacteria and the health of the human intestine itself.

“Bacteriophages … deeply influence microbial communities by functioning as vectors of horizontal gene transfer, encoding accessory benefit functions for host bacterial species and promoting dynamic co-evolutionary interactions”, write the researchers in their new article.

For a long time, our knowledge of this phenomenon has been paralyzed by limitations in our understanding of bacteriophage species.

In recent years, new advances in metagenomic analysis have significantly expanded our awareness of the viral variety we are examining here – and perhaps nothing more than the Gut Phage Database, which researchers describe as a “massive expansion of the diversity of bacteriophages in the human intestine”

“As far as we know, this set represents the most comprehensive and complete collection of human intestinal phage genomes to date,” write the study’s authors.

“Having a comprehensive database of high-quality phage genomes paves the way for a multitude of analyzes of the human gut viroma with much better resolution, allowing the association of specific viral clades with distinct microbiome phenotypes.”

The database is already updating what we know about viral behavior.

Research shows that more than a third (36 percent) of the identified viral clusters are not restricted to infecting a single species of bacteria, which means that they can create gene flow networks in phylogenetically distinct bacterial species.

In addition, the researchers found 280 viral clusters distributed globally, including a newly identified clade, called Gubaphage, which appears to be the second most prevalent virus clade in the human gut, following what is known as the crAssphage group.

Given certain similarities between the two, the researchers initially thought that Gubaphage could belong to a proposed family of viruses similar to crAssphage, before determining that the clades were, in fact, distinct.

There is still a lot to learn, not just about Gubaphage – but about a multitude of viruses that we never dare to dream of. Thanks to research efforts like this, however, tomorrow’s discoveries are closer and new insights will come faster.

“Bacteriophage research is currently undergoing a renaissance,” says microbiologist Trevor Lawley of the Wellcome Sanger Institute.

“This high-quality, large-scale catalog of human gut viruses arrives at the right time to serve as a model to guide ecological and evolutionary analysis in future viroma studies.”

The results are reported in Cell.

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