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Study Reveals Wide Range of Viruses in Human Gut Bacteria

NEW YORK – Researchers from the Wellcome Sanger Institute, the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI), and elsewhere have assembled a large set of genomes from bacteriophages that reside in bacteria and archaea in the human gut.

"It's fascinating to see how many unknown species live in our gut, and to try and unravel the link between them and human health," co-first author Alexandre Almeida, a postdoctoral researcher affiliated with EMBL-EBI and Sanger, said in a statement.

The team's Gut Phage Database — described in a study published in Cell on Thursday — currently contains more than 142,800 viral genomes from gut phages found in some 28,060 human gut metagenome sequence sets and reference genome sequence data for almost 2,900 cultured gut bacteria. The collection includes a newly identified cluster of bacteriophages dubbed the Gubaphage clade that appeared to stem from a shared common ancestor and was potentially enriched in bugs from the Bacteroidales bacterial order.

"This high-quality, large-scale catalogue of human gut viruses comes at the right time to serve as a blueprint to guide ecological and evolutionary analysis in future virome studies," senior author Trevor Lawley, a host-microbiota research group leader at the Sanger Institute, said in a statement, noting that bacteriophage research "is currently experiencing a renaissance."

Using the VirFinder and VirSorter algorithms, together with a machine-learning method to remove unrelated mobile genetic elements, the investigators searched for phage-like viral sequences in tens of millions of sequence contigs in human gut metagenome data. The previously generated data came from individuals in 28 countries on half a dozen continents.

Their search came up with 142,809 non-redundant gut phage sequences. More than one-third of the viral clusters were found in more than one host species. Bacteria from the Firmicutes phylum appeared to be home to the most diverse phage collections, though the analyses also highlighted phages in host bacteria from the Bacteroidota, Proteobacteria, and Actinobacteriota phyla.

"High-quality viral genomes pave the way to better understand what role viruses play in our gut microbiome, including the discovery of new treatments such as antimicrobials from bacteriophage origin," co-first author Luis Camarillo-Guerrero, a host-microbiota interactions researcher at the Wellcome Sanger Institute, said in a statement.

The data pointed to the presence of at least 280 viral clusters in microbes from the human gut — groups of related phages that turned up in gut samples from individuals tested at sites around the world in subsequent epidemiological analyses. Even so, the analysis pointed to the presence of distinct clusters that distinguished the "phageomes" in North America, Europe, and Asia compared to those in Africa and South America that, in turn, seemed to coincide with gut microbe differences.

"Given the correlation between microbiome enterotypes and phageome types, driven by the intimate connection between phages and their bacterial hosts, we provide evidence that human lifestyle is associated with global variation of gut phageomes, most likely mediated by differences in the host gut microbiome," the authors wrote.

While such bacteriophages may influence the abundance and activity of microbes in the gut, the researchers noted that the types of viruses found in gut bacteria are distinct from viral pathogens behind COVID-19 and other human infections.

"[M]ost of the viruses we found have DNA as their genetic material, which is different from the pathogens most people know, such as SARS-CoV-2 or Zika, which are RNA viruses," Almeida said in a statement, adding that the samples scrutinized for the study "came mainly from healthy individuals who didn't share any specific diseases."

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