Tens of Thousands of Viruses Discovered in Human Poop
In a study published today in Nature Microbiology, researchers identified 54,118 virus species that live in the human stomach, with 92 percent of them previously unknown.
However, as we and our collaborators at the Joint Genome Institute and Stanford University in California discovered, the vast majority of these were bacteriophages, or “phages” These viruses “eat” bacteria and are incapable of infecting human cells.
When the majority of us think of viruses, we think of organisms that cause diseases such as mumps, measles, or, more recently, COVID-19. However, human bodies contain a large number of these minute parasites that prey on the germs that reside there.
Everybody defecates (but not all poop is the same)
Recently, there has been a surge of interest in the human gut microbiome: the group of bacteria that live in our gastrointestinal tract.
Apart from assisting us in digesting our food, these microorganisms play a variety of other critical activities. They protect us from dangerous microorganisms, regulate our mental health, prepare our immune system as youngsters, and continue to play a role in immunological control throughout adulthood.
It is safe to state that the human gut is now the world’s most researched microbial ecology. Despite this, more than 70% of the microbial species that live there have not been cultured in the laboratory.
We know this because a technique called metagenomics allows us to access the genetic blueprints of the gut microbiome. This is a highly effective approach in which DNA is collected straight from the environment and randomly sequenced, providing us with a snapshot of what is present and what it may be doing.
Metagenomic research have demonstrated how far we still need to go in cataloguing and isolating all microbial species found in the human gut – and even further in the case of viruses.
11,810 feces samples
We and our colleagues computationally extracted viral sequences from 11,810 publically available fecal metagenomes from individuals in 24 different countries for our new research. We sought to determine the extent to which viruses had colonized the human intestine.
This effort resulted in the creation of the Metagenomic Gut Virus catalog, the most comprehensive resource of its kind to date. This collection contains 189,680 viral genomes representing over 50,000 unique viral species.
Surprisingly (or perhaps unexpectedly), over 90% of these viral species are unknown to science. They jointly encode over 450,000 unique proteins, representing a vast reservoir of functional potential that may be useful or destructive to their microbial, and ultimately human, hosts.
Additionally, we examined subspecies of various viruses and discovered that several displayed notable regional patterns throughout the 24 nations surveyed.
For example, a recently characterized and intriguing crAssphage subspecies was abundant in Asia but was rare or nonexistent in European and North American samples. This could be a result of the virus’s restricted spread within specific human populations.
During our molecular field trip, one of the most often discovered functions was that of diversity-generating retroelements (DGRs). These are a class of genetic elements that alter certain target genes in order to generate favorable variation for the host. This may aid viruses in their continuous evolutionary arms race with their bacterial hosts in the case of DGRs.
Surprisingly, we discovered that one-third of the most frequently encoded viral proteins have unknown activities, including over 11,000 genes associated to “beta-lactamases” which confer resistance to antibiotics such as penicillin.
Establishing a link between gut viruses and their bacteria hosts
After identifying the phages, we needed to connect them to their microbial hosts. CRISPRs, which are best recognized for their numerous applications in gene editing, are bacterial immune systems that “remember” previous viral infections and work to prevent them from recurring.
They accomplish this by copying and storing bits of the invading virus into their own genomes, which may then be utilized to target and eliminate the virus specifically in future encounters.
We used this historical record of attacks to connect a large number of viral genomes to their hosts in the gut ecosystem. Unsurprisingly, very abundant viral species were associated with highly abundant bacterial species in the gut, the majority of which were members of the Firmicutes and Bacteroidota phyla.
So, what are we to do with all of this fresh data? Phage treatment is one promising application of a database of gut viruses and their hosts. Phage therapy is an ancient notion that predates antibiotics, in which viruses are employed to treat illnesses by specifically targeting bacterial pathogens.
There has been debate about potentially tailoring people’s gut microbiomes to enhance their health by dietary changes, probiotics, prebiotics, or even “transpoosions” (fecal microbiota transplants).
Phage therapy may contribute to this goal by increasing the precision of microbiome manipulation at the species or even subspecies level. For instance, the bacterial pathogen Clostridioides difficile (or Cdiff for short) is a major cause of hospital-acquired diarrhea and might be targeted particularly by phages.
Phage treatment may enable more nuanced modulation of non-pathogenic bacterial populations in the gut. A comprehensive compendium of gut viruses is an excellent starting point for pursuing such applicable goals.
It is worth emphasizing, however, that estimations based on our findings indicate that we have examined only a percentage of total gut viral diversity. As a result, we still have a long way to go.
Philip Hugenholtz, Professor of Microbiology at the University of Queensland’s School of Chemistry and Molecular Biosciences, and Soo Jen Low, Postdoctoral Research Fellow at the University of Queensland.
The Conversation has republished this article under a Creative Commons license. Continue reading the original story.