It is important to understand how viruses living in the gut affect human health. Imbalances in our gut microbiome can contribute to diseases and conditions such as obesity, inflammatory bowel disease, and allergies. There is a need to understand the role our gut bacteria, and the bacteriophages that infect them, play in human health and disease. Now researchers at Wellcome Sanger Institute and EMBL’s European Bioinformatics Institute (EMBL-EBI) report they have identified 140,000 viral species living in the human gut, with more than half of which have never been seen before.

Their findings, “Massive expansion of human gut bacteriophage diversity,” were published in the journal Cell.

“Bacteriophages drive evolutionary change in bacterial communities by creating gene flow networks that fuel ecological adaptions,” wrote the researchers. “However, the extent of viral diversity and its prevalence in the human gut remains largely unknown. Here, we introduce the Gut Phage Database (GPD), a collection of ∼142,000 nonredundant viral genomes (>10 kb) obtained by mining a dataset of 28,060 globally distributed human gut metagenomes and 2,898 reference genomes of cultured gut bacteria.”

Using metagenomics, the researchers explored and cataloged the biodiversity of the viral species found in 28,060 public human gut metagenomes and 2,898 bacterial isolate genomes cultured from the human gut.

“It’s important to remember that not all viruses are harmful, but represent an integral component of the gut ecosystem,” explained Alexandre Almeida, PhD, postdoctoral fellow at EMBL-EBI and the Wellcome Sanger Institute. “For one thing, most 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. Secondly, these samples came mainly from healthy individuals who didn’t share any specific diseases. 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.”

A group of viruses believed to have a common ancestor was identified, which the researchers refer to as the Gubaphage. This was found to be the second most prevalent virus clade in the human gut, after the crAssphage, which was discovered in 2014.

Both of these viruses seem to infect similar types of human gut bacteria, but without further research, it is difficult to know the exact functions of the newly discovered Gubaphage.

“An important aspect of our work was to ensure that the reconstructed viral genomes were of the highest quality,” Luis F. Camarillo-Guerrero, a PhD student at the Wellcome Sanger Institute and first author of the study, added. “A stringent quality control pipeline coupled with a machine learning approach enabled us to mitigate contamination and obtain highly complete viral genomes. 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.”

The results of the study form the basis of the GPD, which will be a resource for those studying bacteriophages and the role they play in regulating the health of both our gut bacteria and ourselves.

“Bacteriophage research is currently experiencing a renaissance. This high-quality, large-scale catalog of human gut viruses comes at the right time to serve as a blueprint to guide ecological and evolutionary analysis in future virome studies,” noted Trevor Lawley, senior author of the study from the Wellcome Sanger Institute.

“…we believe that further characterization of other prominent genetic elements such as ICEs, integrative mobilizable elements (IMEs), genetic islands, and transposons will bring us closer to understanding the association of the gut microbiome with different lifestyles, age, and, ultimately, health and disease,” concluded the researchers.

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