Every human gut has a viral ‘fingerprint’

Each person’s gut virus makeup is as unique as a fingerprint, according to the first study to assemble a comprehensive database of viral populations in the human digestive system.

Analysis of viruses in the intestines of healthy westerners also showed that dips and peaks in virus type diversity between childhood and old age reflect bacterial changes over the course of the life cycle.

The Gut Virome Database developed by scientists at Ohio State University identifies 33,242 unique viral populations found in the human gut. (A collection of viruses like those in the human gut is called a virome.) This is not a cause for concern: most viruses do not cause disease.

In fact, the more scientists learn about viruses, the more they see them as part of the human ecosystem – suggesting that viruses have the potential to represent a new class of drugs that could fight pathogenic bacteria, by especially those resistant to antibiotics. Better knowledge of viruses in the intestinal environment could even improve our understanding of the gastrointestinal symptoms experienced by some of the sickest COVID-19 patients.

The researchers plan to regularly update the open access database.

“We’ve established a solid starting point to see what the virome looks like in humans,” said study co-author Olivier Zablocki, postdoctoral researcher in microbiology at Ohio State. “If we can characterize the viruses that keep us healthy, we might be able to harness this information to design future therapies for pathogens that cannot otherwise be treated with drugs.”

The study is published today (August 24) in the journal Cell host and microbe.

Talking about the good and bad bacteria in the gut microbiome is commonplace these days, but viruses in the gut – and everywhere – are difficult to detect because their genomes do not contain a signature gene sequence common to that of genomes. bacteria. The vast sequence space of viruses remains so unexplored that it is often referred to as “dark matter”.

For this work, the researchers began with data from 32 studies spanning about a decade that looked at intestinal viruses in a total of 1,986 healthy and sick people in 16 countries. Using techniques to detect viral genomes, the team identified more than 33,000 different viral populations.

“We used machine learning on known viruses to help us identify unknown viruses,” said first author Ann Gregory, who completed the work while a graduate student at Ohio State. “We were interested in how many types of viruses we could see in the gut, and we determined it by how many types of genomes we could see since we couldn’t visually see viruses.”

Their analysis confirmed the results of smaller studies suggesting that although a few viral populations have been shared among a subset of people, there is no major group of gut viruses common to all humans.

However, some trends have been identified. In healthy Western individuals, age influences the diversity of viruses in the gut, which increases dramatically from childhood to adulthood, then decreases after 65 years. The pattern matches what is known about the ebb and flow of gut bacterial diversity with one exception: infant guts underdeveloped immune systems are teeming with types of viruses, but few varieties of bacteria.

People living in non-Western countries had a greater diversity of intestinal viruses than Westerners. Gregory said other research has shown that non-Western people who move to the United States or another Western country lose this microbiome diversity, which suggests that food and the environment are causing the virome differences. (For example, scientists have found intact plant viruses in the gut – the only way they can achieve this is through diet.) Variations in viral diversity could also be seen in healthy participants compared to patients in the 32 studies analyzed.

“A general rule of thumb for ecology is that greater diversity leads to a healthier ecosystem,” Gregory said. “We know that a greater diversity of viruses and microbes is generally associated with a healthier individual. And we’ve seen that healthier individuals tend to have a greater diversity of viruses, indicating that these viruses can potentially do something positive and have a beneficial role. “

Almost all of the populations – 97.7 percent – were phages, which are viruses that infect bacteria. Viruses do not have a function without a host – they drift through one environment until they infect another organism, taking advantage of its properties to reproduce. The most studied viruses kill their host cells, but scientists at the Ohio State laboratory in which Gregory and Zablocki worked have found more and more phage-like viruses that coexist with their host microbes and even produce genes that help host cells compete and survive. .

The head of that lab, study lead author Matthew Sullivan, is focusing on “phage therapy” – the 100-year-old idea of ​​using phages to kill antibiotic-resistant pathogens or superbugs.

“Phages are part of a large, interconnected network of organisms that live with and on us, and when broad-spectrum antibiotics are used to fight infection, they also harm our natural microbiome,” Sullivan said. . “We are developing a toolkit to expand our understanding and ability to use phages to bring disrupted microbiomes back to a healthy state.

“It is important to note that such therapy is expected to impact not only our human microbiome, but also other animals, plants and technical systems to combat pathogens and superbugs.” They could also lay the groundwork for something we may have to consider in the world’s oceans to fight. climate change.”

A professor of microbiology and civil, environmental, and geodesic engineering, Sullivan has helped establish interdisciplinary research collaborations at Ohio State. He recently founded and directs the new Ohio State Center of Microbiome Science and co-directs the Microbial Communities program at the Infectious Diseases Institute.

Zablocki noted that there is still a lot to be learned about the functions of viruses in the gut – both beneficial and harmful.

“I see him as the chicken and the egg,” he said. “We see the disease and we see the structure of the community. Is it because of this community structure that the disease has arisen, or is it that the disease is the origin of the community structure that we see? standardized data set will allow us to pursue these questions. ”