Understanding the role of viruses in the human gut

2 June 2022

Viruses have been in our lives and news-feeds almost incessantly in the last two years. We have been double-jabbed and masked for much of this time in an effort to avoid the SARS-CoV-2 virus. As we have learnt, these steps can limit the spread of COVID-19 disease and help us avoid SARS-CoV-2 infection.

But can we avoid viruses entirely? The simple answer is no. Reality is much more complex, and viruses are the most abundant units of life on earth. We are, in fact, great stores of viruses ourselves, with some viruses being beneficial for us.

The sole purpose of a virus's life is to multiply, but the irony is that it cannot multiply on its own. It could be argued that multiplication is also our main objective in life. However, unlike humans and most other forms of life, viruses do not have the capability to recreate the parts they need to reproduce. Instead, they must rely on the cellular machinery from more advanced forms of life — bacteria, plants, or animals.

How many viruses in total are there in the world at any time? An estimated 10³¹—10 with 30 zeros after it is the figure that has been bandied about — a number so enormous that we cannot truly appreciate what it means. How many types of viruses are there? To use the phrase that the US politician Donald Rumsfeld has become famous for, "This is a case of unknown unknowns." There are so many types of viruses occupying so many different hosts and ecosystems that we have no idea of how many categories of viruses there are.

Humans carry an astronomical number of viruses all the time. These viruses do not kill us because their targets are the billions of bacteria that reside in our bodies, principally in the gut. This is also an area that requires a lot of research, and we are only just getting to know about the different types of bacteria in our guts. So, we are a long way from identifying all the viruses in our guts that target these different types of bacteria.

Regardless, people have made a start. The new sequencing technologies allow us to analyse different types of DNA sequences from complex mixtures in a way that would have been unimaginable ten years ago. A major problem is isolating the viruses' DNA from the much greater amount of DNA from other organisms that often contaminate such preparations. Viruses that use RNA instead of DNA as their genetic material present another set of difficulties.

A recent paper from Chuen Zhang Lee, an Honours student at Monash University Malaysia, reports progress in identifying bacterial viruses in our guts by using human faeces as the starting material. Chuen used faecal matter from two Malaysian Orang Asli groups, the Jehai and the Jakun, to show that the viruses they contain are different from viruses in more frequently studied groups, such as Europeans or Chinese.

Chuen enriched the viruses in the faeces (as an indicator of what is actually in the gut) away from all the yucky material, bacterial cells and human cells and extracted the genetic material from this virus enriched material. The viral DNA was then sequenced at the Monash University Malaysia Genomics Facility using a technique that allows one to read long stretches of DNA.

Using this method, Chuen recognised approximately half the DNA as coming from known viruses. The remaining half of the DNA sequences did not come from known viral sequences and might be from viruses that people had not studied before.

Chuen could identify what some of the sample-givers had consumed and their lifestyle and environment based on the viruses he found. He also identified some of the bacteria in our guts these viruses could attack and, thus, get a partial picture of what types of bacteria could be in our guts.

These results start to build up a picture of how our gut health is determined, which can significantly determine our overall health. It is clear that viruses may also have a role in determining gut health, a complex topic.

Further analysis is required before the sequences can be declared as coming from new viruses. Perhaps some of these viruses may turn out to be helpful in controlling bacteria, as has been shown by Dr Jeremy Barr's group with a known virus and problematic bacteria.

Chuen was supervised by a group of researchers including Professor Maude Phipps from the Jeffrey Cheah School of Medicine and Health Sciences, Dr Jeremy Barr from Monash University School of Biological Sciences and Professor Qasim Ayub, Professor Sunil Lal and Professor Sadequr Rahman from the School of Science. Muhammad Zarul Hanifah, who worked at the Genomics Facility, assisted Chuen in analysing his data. Chuen's work entitled "The gut virome in two indigenous populations from Malaysia '' has been published in the prestigious Nature publication, Scientific Reports (https://www.nature.com/articles/s41598-022-05656-3).

Viruses are clearly 'cool' and 'hot' right now, and they are likely to remain that way for a long time. We look forward to furthering discoveries on viruses and insights into how they can be used to our benefit.