We found more than 54,000 viruses in people’s poo — and 92% were previously unknown to science


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Philip Hugenholtz, The University of Queensland and Soo Jen Low, The University of QueenslandResearch published today in Nature Microbiology has identified 54,118 species of virus living in the human gut — 92% of which were previously unknown.

But as we and our colleagues from the Joint Genome Institute and Stanford University in California found, the great majority of these were bacteriophages, or “phages” for short. These viruses “eat” bacteria and can’t attack human cells.

When most of us think of viruses, we think of organisms that infect our cells with diseases such as mumps, measles or, more recently, COVID-19. However, there are a vast number of these microscopic parasites in our bodies — mostly in our gut — that target the microbes that live there.




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Everybody poos (but not all poo is the same)

There has recently been much interest in the human gut microbiome: the collection of microorganisms that live in our gut.

Besides helping us digest our food, these microbes have many other important roles. They protect us against pathogenic bacteria, modulate our mental well-being, prime our immune system when we are children, and have an ongoing role in immune regulation into adulthood.

It’s fair to say the human gut is now the most well-studied microbial ecosystem on the planet. Yet more than 70% of the microbial species that live there have yet to be grown in the laboratory.

We know this because we can access the genetic blueprints of the gut microbiome via an approach known as metagenomics. This is a powerful technique whereby DNA is directly extracted from an environment and randomly sequenced, giving us a snapshot of what is present within and what it might be doing.

Biologists estimate there are a few hundred trillion viruses living within and outside our bodies.
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Metagenomic studies have revealed how far we still have to go to catalogue and isolate all the microbial species in the human gut — and even further to go when it comes to viruses.

11,810 samples of poo

In our new research, we and our colleagues computationally mined viral sequences from 11,810 publicly available faecal metagenomes, taken from people in 24 different countries. We wanted to get an idea of the extent to which viruses have taken up residence in the human gut.

This effort resulted in the Metagenomic Gut Virus catalogue, the largest such resource to date. This catalogue comprises 189,680 viral genomes which represent more than 50,000 distinct viral species.

Remarkably (but perhaps predictably), more than 90% of these viral species are new to science. They collectively encode more than 450,000 distinct proteins — a huge reservoir of functional potential that may either be beneficial or detrimental to their microbial, and in turn human, hosts.

We also drilled down into subspecies of different viruses and found some showed striking geographical patterns across the 24 countries surveyed.

For example, a subspecies of the recently described and enigmatic crAssphage was prevalent in Asia, but was rare or absent in samples from Europe and North America. This may be due to localised expansion of this virus in specific human populations.

One of the most common functions we discovered in our molecular field trip were diversity-generating retroelements (DGRs). These are a class of genetic elements that mutate specific target genes in order to generate variation that can be beneficial to the host. In the case of DGRs in viruses, this may help in the ongoing evolutionary arms race with their bacterial hosts.

Intriguingly, we found one-third of the most common virally-encoded proteins have unknown functions, including more than 11,000 genes distantly related to “beta-lactamases”, which enable resistance to antibiotics such as penicillin.

Linking gut viruses to their microbial hosts

Having identified the phages, our next task was to link them to their microbial hosts. CRISPRs, best known for their many applications in gene editing, are bacterial immune systems that “remember” past viral infections and prevent them from happening again.

They do this by copying and storing fragments of the invading virus into their own genomes, which can then be used to specifically target and destroy the virus in future encounters.

We used this record of past attacks to link many of the viral sequences to their hosts in the gut ecosystem. Unsurprisingly, highly abundant viral species were linked to highly abundant bacterial species in the gut, mostly belonging to the bacterial phyla Firmicutes and Bacteroidota.

So what can we do with all of this new information? One promising application of an inventory of gut viruses and their hosts is phage therapy. Phage therapy is an old concept predating antibiotics, in which viruses are used to selectively target bacterial pathogens in order to treat infections.

There has been discussion of potentially customising people’s gut microbiomes using dietary interventions, probiotics, prebiotics or even “transpoosions” (faecal microbiota transplants), to improve an individual’s health.

Phage therapy may be a useful addition to this objective, by adding species or even subspecies-level precision to microbiome manipulation. For example, the bacterial pathogen Clostridioides difficile (or Cdiff for short) is a leading cause of hospital-acquired diarrhoea that could be specifically targeted by phages.

More subtle manipulation of non-pathogenic bacterial populations in the gut may be achievable through phage therapy. A complete compendium of gut viruses is a useful first step for such applied goals.

It’s worth noting, however, that projections from our data suggest we’ve only investigated a fraction of the total gut viral diversity. So we’ve still got a long way to go.




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The Conversation


Philip Hugenholtz, Professor of Microbiology, School of Chemistry and Molecular Biosciences, The University of Queensland and Soo Jen Low, Postdoctoral Research Fellow, The University of Queensland

This article is republished from The Conversation under a Creative Commons license. Read the original article.

How to prepare and protect your gut health over Christmas and the silly season



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Claus T. Christophersen, Edith Cowan University

It’s that time of year again, with Christmas parties, end-of-year get-togethers and holiday catch-ups on the horizon for many of us — all COVID-safe, of course. All that party food and takeaway, however, can have consequences for your gut health.

Gut health matters. Your gut is a crucial part your immune system. In fact, 70% of your entire immune system sits around your gut, and an important part of that is what’s known as the gut-associated lymphoid tissue (GALT), which houses a host of immune cells in your gut.

Good gut health means looking after your gut microbiome — the bacteria, fungi, viruses and tiny organisms that live inside you and help break down your food — but also the cells and function of your gastrointestinal system.

We know gut health can affect mood, thanks to what’s known as the gut-brain axis. But there’s also a gut-lung axis and a gut-liver axis, meaning what happens in your gut can affect your respiratory system or liver, too.

Here’s what you can do to bolster your gut microbiome in the coming weeks and months.




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How do silly season indulgences affect our gut health?

You can change your gut microbiome within a couple of days by changing your diet. And over a longer period of time, such as the Christmas-New Year season, your diet pattern can change significantly, often without you really noticing.

That means we may be changing the organisms that make up our microbiome during this time. Whatever you put in will favour certain bacteria in your microbiome over others.

We know fatty, sugary foods promote bacteria that are not as beneficial for gut health. And if you indulge over days or weeks, you are pushing your microbiome towards an imbalance.

A group of friends clink drinks while wearing Christmas gear.
For many of us, Christmas is a time of indulgence.
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Is there anything I can do to prepare my gut health for the coming onslaught?

Yes! If your gut is healthy to begin with, it will take more to knock it out of whack. Prepare yourself now by making choices that feed the beneficial organisms in your gut microbiome and enhance gut health.

That means:

  • eating prebiotic foods such as jerusalem artichokes, garlic, onions and a variety of grains and inulin-enhanced yoghurts (inulin is a prebiotic carbohydrate shown to have broad benefits to gut health)

  • eating resistant starches, which are starches that pass undigested through the small intestine and feed the bacteria in the large intestine. That includes grainy wholemeal bread, legumes such as beans and lentils, firm bananas, starchy vegetables like potatoes and some pasta and rice. The trick to increasing resistant starches in potato, pasta and rice is to cook them but eat them cold. So consider serving a cold potato or pasta salad over Christmas

  • choosing fresh, unprocessed fruits and vegetables

  • steering clear of added sugar where possible. Excessive amounts of added sugar (or fruit sugar from high consumption of fruit) flows quickly to the large intestine, where it gets gobbled up by bacteria. That can cause higher gas production, diarrhoea and potentially upset the balance of the microbiome

  • remembering that if you increase the amount of fibre in your diet (or via a supplement), you’ll need to drink more water — or you can get constipated.

For inspiration on how to increase resistant starch in your diet for improved gut health, you might consider checking out a cookbook I coauthored (all proceeds fund research and I have no personal interest).

Good gut health is hard won and easily lost.
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What can I do to limit the damage?

If Christmas and New Year means a higher intake of red meat or processed meat for you, remember some studies have shown that diets higher red meat can introduce DNA damage in the colon, which makes you more susceptible to colorectal cancer.

The good news is other research suggests if you include a certain amount of resistant starch in a higher red meat diet, you can reduce or even eliminate that damage. So consider a helping of cold potato salad along with a steak or sausage from the barbie.

Don’t forget to exercise over your Christmas break. Even going for a brisk walk can get things moving and keep your bowel movements regular, which helps improve your gut health.

Have a look at the Australian Guide to Healthy Eating and remember what foods are in the “sometimes” category. Try to keep track of whether you really are only having these foods “sometimes” or if you have slipped into a habit of having them much more frequently.

The best and easiest way to check your gut health is to use the Bristol stool chart. If you’re hitting around a 4, you should be good.

An image of the Bristol stool chart
If you’re hitting around a 4, you should be good.
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Remember, there are no quick fixes. Your gut health is like a garden or an ecosystem. If you want the good plants to grow, you need to tend to them — otherwise, the weeds can take over.

I know you’re probably sick of hearing the basics — eat fruits and vegetables, exercise and don’t make the treats too frequent — but the fact is good gut health is hard won and easily lost. It’s worth putting in the effort.

A preventative mindset helps. If you do the right thing most of the time and indulge just now and then, your gut health will be OK in the end.The Conversation

Claus T. Christophersen, Senior Lecturer, Edith Cowan University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Diarrhoea, stomach ache and nausea: the many ways COVID-19 can affect your gut



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Vincent Ho, Western Sydney University

Media reports earlier this week described a Queensland nurse with stomach pains who went on to test positive for COVID-19.

Could stomach pains be another symptom of COVID-19? And if you have stomach pains, should you get tested?

Although we might think of COVID-19 as a respiratory disease, we know it involves the gut. In fact SARS-CoV-2, the virus that causes COVID-19, enters our cells by latching onto protein receptors called ACE2. And the greatest numbers of ACE2 receptors are in the cells that line the gut.

COVID-19 patients with gut symptoms are also more likely to develop severe disease. That’s partly because even after the virus has been cleared from the respiratory system, it can persist in the gut of some patients for several days. That leads to a high level of virus and longer-lasting disease.

We also suspect the virus can be transmitted via the faecal-oral route. In other words, the virus can be shed in someone’s poo, and then transmitted to someone else if they handle it and touch their mouth.




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What type of gut symptoms are we talking about?

A review of more than 25,000 COVID-19 patients found about 18% had gastrointestinal symptoms. The most common was diarrhoea followed by nausea and vomiting. Abdominal pain was considered rare. In another study only about 2% of COVID-19 patients had abdominal pain.

Some people believe COVID-19 causes abdominal pain through inflammation of the nerves of the gut. This is a similar way to how gastroenteritis (gastro) causes abdominal pain.

Another explanation for the pain is that COVID-19 can lead to a sudden loss of blood supply to abdominal organs, such as the kidneys, resulting in tissue death (infarction).

Are gut symptoms recognised?

The US Centers for Disease Control has added diarrhoea, nausea and vomiting to its list of recognised COVID-19 symptoms.

However, the World Health Organisation still only lists diarrhoea as a gastrointestinal COVID-19 symptom.

In Australia, nausea, diarrhoea and vomiting are listed as other COVID-19 symptoms, alongside the classic ones (which include fever, cough, sore throat and shortness of breath). But abdominal pain is not listed.

Advice about symptoms that warrant testing may vary across states and territories.

How likely is it?

Doctors often use the concept of pre-test probability when working out if someone has a particular disease. This is the chance a person has the disease before we know the test result.

What makes it difficult to determine the pre-test probability for COVID-19 is we don’t know how many people in the community truly have the disease.

We do know, however, COVID-19 in Australia is much less common than in many other countries. This affects the way we view symptoms that aren’t typically associated with COVID-19.

It’s far more common for people’s abdominal pain to be caused by something other than COVID-19. For example, about a quarter of people at some point in their lives are known to suffer from dyspepsia (discomfort or pain in the upper abdomen). But the vast majority of people with dyspepsia do not have COVID-19.

Similarly, irritable bowl syndrome affects about 9% of Australians, and causes diarrhoea. Again, the vast majority of people with irritable bowel syndrome do not have COVID-19.

So how about this latest case?

In the Queensland case, we know the nurse was worried he could have had COVID-19 because he was in close contact with COVID-19 patients.

As he seemed otherwise healthy before developing new abdominal symptoms, and considering he worked on a COVID ward, his pre-test probability was high. Doctors call this a “high index of suspicion” when there is a strong possibility someone may have symptoms due to a disease such as COVID-19.

What does this mean for me?

If you have new gastrointestinal symptoms and you’ve potentially been in contact with someone with COVID-19 or if you also have other classic COVID-19 symptoms (fever, cough, shortness of breath and sore throat) you should definitely get tested.

If you have just gastrointestinal symptoms, you may need to get tested if you’re in a “hotspot” area, or work in a high-risk occupation or industry.

If you have gastrointestinal symptoms alone, without any of these additional risk factors, there is no strong evidence to support testing.




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However, if COVID-19 becomes even more common in the community, these symptoms now regarded as uncommon for COVID-19 will become more common.

If you have concerns about any gastrointestinal symptoms, seeing your GP would be sensible. Your GP will provide a balanced assessment based on your medical history and risk profile.




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The Conversation


Vincent Ho, Senior Lecturer and clinical academic gastroenterologist, Western Sydney University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

We don’t know for sure if coronavirus can spread through poo, but it’s possible



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Vincent Ho, Western Sydney University

While we most commonly associate COVID-19 with fever and cough, gastrointestinal symptoms including diarrhoea, vomiting and abdominal pain are not unheard of in people who contract coronavirus.

This is likely because SARS-CoV-2, the virus that causes COVID-19, is found in the gut as well as the respiratory tract.

Importantly, the gut’s involvement in coronavirus illness points to the possibility COVID-19 could spread through faeces.

At this stage we don’t know for certain whether or not that occurs – but we can take precautions anyway.




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Coronavirus and the gut

SARS-CoV-2 gains entry into human cells by latching onto protein receptors called ACE2, which are found on certain cells’ surfaces.

Around 2% of the cells lining the respiratory tract have ACE2 receptors, while they’re also found in the cells lining the blood vessels.

But the greatest numbers of ACE2 receptors are actually found in the cells lining the gut. Around 30% of cells lining the last part of the small intestine (called the ileum) contain ACE2 receptors.

Coronavirus gets into our cells by latching on to ACE2 receptors.
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Clinicians have detected coronavirus in tissue taken from the lining of the gut (oesophagus, stomach, small bowel and rectum) through routine procedures such as endoscopy and colonoscopy, where we use cameras to look inside the body. They found abundant ACE2 receptors in those tissue samples.

While some researchers have proposed alternative explanations, it’s likely people with COVID-19 experience gastrointestinal symptoms because the virus directly attacks the gut tissue through ACE2 receptors.

How common are gastrointestinal symptoms?

Data from 55,000 COVID-19 cases in China has shown the most common gastrointestinal symptom, diarrhoea, occurs in only 3.7% of those affected.

But there’s emerging evidence gastrointestinal symptoms such as diarrhoea may actually be more common, particularly among patients who develop more serious disease.

In one study of 204 patients diagnosed with COVID-19 at three different hospitals in the Hubei province in China, almost 20% of patients had at least one gastrointestinal symptom (diarrhoea, vomiting or abdominal pain).




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The researchers found gastrointestinal symptoms became more severe as the COVID-19 illness worsened. And patients with gastrointestinal symptoms were less likely to recover than those without gastrointestinal symptoms.

The reason for this is not clear but one possibility is patients with a higher density of virus, or viral load, are more likely to have coronavirus wreak havoc in their gut.

Coronavirus in our poo

The presence of coronavirus in the gut and the gastrointestinal symptoms associated with COVID-19 suggest coronavirus could be spread via faecal-oral transmission. This is when virus in the stool of one person ends up being swallowed by another person.

A recent study from China found just over half of 73 hospitalised patients with COVID-19 had virus in their faeces. Many of them did not have gastrointestinal symptoms.

While testing stool samples may not be an efficient way to diagnose COVID-19 in individuals – it’s normally slower than testing samples from the respiratory tract – researchers are looking at poo to detect population outbreaks of coronavirus.

More than a dozen research groups worldwide are collaborating on a project analysing wastewater for the presence of coronavirus in target populations.

But just because the virus is found in faeces, it doesn’t mean it’s necessarily infectious when shed from the stool. We need more research to ascertain whether this is the case.




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The virus seems to last longer in faeces

One study in China followed 74 COVID-19 patients in hospital by taking throat swabs and faecal samples daily or every second day.

The researchers found in over half of patients, their faecal samples remained positive for coronavirus for an average of just over 11 days after their throat swabs tested negative. Coronavirus was still detected in one patient’s faeces 33 days after their throat swab had turned negative.

This suggests the virus is still actively reproducing in the patient’s gastrointestinal tract long after the virus has cleared from the respiratory tract.

So if coronavirus can transmit via the faecal-oral route, we’ll want to know about it.

Sewage could offer clues about coronavirus transmission.
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In order to prove coronavirus can transmit via the faecal-oral route we’d need to see larger cohort studies.

These studies would include gathering more information on how well the coronavirus survives in the gut, how it causes gastrointestinal symptoms like diarrhoea and how the virus survives in faeces at different temperatures.

Researchers have found live coronavirus in faecal cultures grown in the lab, but this was only in two patients, so other research teams will need to reliably confirm the presence of infectious virus in faeces.

Take precautions anyway

In one study, researchers collected samples from the bathroom of a COVID-19 positive patient with no diarrhoea. Samples from the surface of the toilet bowl, sink and door handle returned positive for the presence of the coronavirus.

So effective handwashing, particularly after using the toilet, is critical.

We know coronavirus can survive for up to three days on plastic and stainless-steel surfaces. So it’s sensible to regularly disinfect surfaces that will be touched when using shared toilets including doorknobs, door handles, taps, support rails and toilet control handles.




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Finally, flush the toilet with the lid closed. This is particularly important for public toilets in communities where there is sustained transmission of coronavirus.

Flushing a toilet creates a phenomenon known as toilet plume where up to 145,000 aerosolised droplets can be released and suspended in the air for hours.

Scientists believe the infectious viral gastroenteritis caused by norovirus can be transmitted in aerosol form through toilet plumes. Coronavirus may be able to do the same. Closing the lid when flushing can prevent around 80% of these infectious droplets from escaping into the air.The Conversation

Vincent Ho, Senior Lecturer and clinical academic gastroenterologist, Western Sydney University

This article is republished from The Conversation under a Creative Commons license. Read the original article.