Viral diversity in the gut of healthy infants

Disease and treatment 29. jun 2023 3 min Professor Dennis Sandris Nielsen, Senior Scientist Shiraz Shah Written by Kristian Sjøgren

A major survey has determined all the viruses present in the intestines of 647 healthy babies, revealing unexpectedly large viral diversity. A researcher says that little is known about the effects of more than 10,000 viruses in the gut of healthy infants.

The composition of gut bacteria in the first year of life strongly influences the development and shaping of the immune system. This composition is then regulated by bacteriophages: viruses present in the intestines that live on bacteria.

For the first time, researchers mapped the virome – the diversity of viruses – in the gut of healthy infants during the period of life when the immune system develops and can have an impact on, among other things, influence the development of autoimmune diseases such as asthma and chronic inflammatory bowel disease.

The research uncovered more than 10,000 virus species in the gut of 647 healthy infants and found that science only knows the function of a handful of them.

“In this study, we opened the lid to a wealth of information about what happens in the gut during a very critical period in life, when the immune system is developed and the seeds for numerous diseases are sown. We also found how the virome of children differs from that of adults, which indicates how the overall community of microorganisms in the gut develops throughout life,” explains a researcher behind the study, Dennis Sandris Nielsen, Professor, Department of Food Science, University of Copenhagen.

The research has been published in Nature Microbiology.

Gut bacteria affect health

Research has gradually established that the gut microbiome influences the maturation of the immune system. The bacteria help to teach the immune system when it should and should not respond. For example, it should respond to harmful bacteria and viruses but not to the beneficial bacteria that live in the gut or to the body’s own cells or pollen.

The immune system should also not attack bacteriophages. When bacteriophages that are very specific in their choice of bacteria attack certain classes of bacteria, they affect not only the presence of the bacteria but also the presence of the metabolites that the bacteria produce, which diffuse across the intestinal wall and into the blood.

Some bacterial metabolites benefit health, including vitamins and short-chain fatty acids. Others harm health and can promote inflammation.

Thus, bacteriophages and their variation strongly influence whether the bacterial community in the gut promotes or harms metabolic health.

“Evidence also indicates that the bacteriophages themselves can affect health independently of the bacteria. Having an inappropriate bacteriome or virome can thus promote the development of many diseases,” says another researcher involved in the study, Shiraz Shah, Senior Scientist, Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, Copenhagen.

Viruses in faecal samples of 647 children

The researchers characterised the viruses in faecal samples from 647 1-year-old infants by separating the viruses from bacteria and anything else in the samples. They then extracted the DNA in the virus fraction and used it to identify the virus species in the gut of the infants.

The researchers identified bacteriophages as well as viruses that have human cells as hosts and identified viruses with double-stranded and single-stranded DNA genomes.

“For many years, we have performed much research on how gut bacteria affect the development of the immune system and overall health, but we have not been able to identify the role of the virome. This study takes a big step in this direction,” explains Dennis Sandris Nielsen.

More than 10,000 virus species

The researchers identified more than 10,000 virus species, the vast majority of which were not previously known. Of the 248 virus families found, only 16 were previously known and 232 were new.

“The most interesting thing is that we found this enormous biodiversity without having any idea how most of these viruses actually affect us,” says Dennis Sandris Nielsen.

The researchers also found that all infants in the study hosted 10–20 species of viruses that infect human cells. Researchers are only now trying to understand the effects of these viruses.

“They probably do not make children very ill and are probably important for the maturation of the immune system, but they may also be a signal for the development of later disease. This needs to be investigated in the future,” adds Shiraz Shah.

Viruses differ among infants and adults

Another important finding was that the viromes of children and adults differ greatly. Some viruses that appear to strongly influence the gut of healthy infants are not present among adults and vice versa.

Some of them make good sense: for example, bacteriophages that attack bacteria of the genus Bifidobacterium, of which children have many more in their intestines than adults. Adults have many more of other viruses, which includes viruses of the Crassvirales order, and these do not seem to affect children about 1 year old.

Finally, the researchers also found that adults have many more of the type of viruses that kill bacteria, whereas children have more of the type of viruses that integrate their DNA into the genetic material of the bacterial cells and multiply each time the bacteria divide.

“But we do not yet know why,” says Shiraz Shah.

More revelations on the way

Dennis Sandris Nielsen says that the study is only one of many studies that will determine the importance and development of the virome in childhood towards adulthood.

The researchers are examining similar faecal samples from the infants when they were 1 week and 1 month old to determine differences even earlier in life and how the entire gut microbiome develops during this period of life, when it most strongly affects the immune system.

In addition, the researchers have compared the findings from their studies with the development of asthma and other diseases among the infants to determine how the virome affects health throughout childhood and into adulthood.

“Now that we know that much of the maturation of the immune system takes place during this period, knowing how the community of viruses that helps to mature the immune system develops and what happens when it develops properly versus improperly is also important. This will also advance knowledge on how to reduce the risk of developing autoimmune diseases,” concludes Dennis Sandris Nielsen.

“Expanding known viral diversity in the healthy infant gut” has been published in Nature Microbiology. The project was funded by the BRIDGE Translational Excellence Programme through the Faculty of Health and Medical Sciences, University of Copenhagen, Joint Programme Initiative (JPI via Innovation Foundation Denmark) and by the Novo Nordisk Foundation. Several authors are affiliated with the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

Dennis Sandris Nielsen's primary fields of research include: - Microbial behavior in complex environments. - The association between the mammalian...

Shiraz Shah studied microbiology and bioinformatics at the Danish Technical University and obtained his Master’s degree in 2006. Since 2007 upon start...

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