Unlocking the code of the ‘super pooper’ could usher in new wave of gut health treatments

Some people donate blood, but Adelaide science account manager and winemaker Matthew Walker-Brown makes scheduled poo donations.

“I thought it’d be a good process to be a part of,” he says.

“Once you do it regularly, your bowels almost run to a clock, so it’s nowhere near as chaotic as you might guess.”

His stool donations are processed and made into medicine that treats a nasty infection of the colon by the bacterium Clostridioides difficile, which can cause diarrhoea, stomach pain and fever.

In 2021, more than 10,000 people were treated for a C. difficile infection in Australia’s hospitals. For those with repeat infections, in most cases antibiotics don’t treat it effectively.

Instead, donations from Mr Walker-Brown and others like him are used in faecal microbiota transplants (FMTs), better known as a poo transplants.

Faecal transplants have been shown to work incredibly well for C. difficile infections and there is hope that they can be used for a much wider range of other conditions.

Despite Mr Walker-Brown’s generosity, it’s hard to convince people to donate their poo. But the future of FMTs may not rely on donors like him at all.

Researchers are now creating a new generation of poo transplants in the lab, that will no longer need a human gut.

And central to their effort is trying to understand, emulate and even improve on the trillions of microbes that live in our colon which are currently so valuable in poo transplants.

The gut microbiome

The human gut is a busy place. Estimates have put the number of bacteria in just one gram of poo at nearly 100 billion, with potentially more than 1,000 species making the colon home.

These bacteria, fungi and other microbes don’t just co-exist with humans; they actively help digest our food for us. For example, some species can turn fibre into short-chain fatty acids, while others make vitamins. 

In the past few decades, scientists have uncovered a wide variety of effects our gut has on the rest of our body and mind. This “second brain” is implicated in everything from bipolar disorder to rheumatoid arthritis. 

Rikeish Muralitharan, a researcher in hypertension at Monash University, has linked the gut microbiome to blood pressure.

“We’ve shown specific diets [that] increase the beneficial by-products that bacteria produce in the gut can also reduce blood pressure,” Dr Muralitharan says. 

“When we have fibre, it reaches the colon and then feeds bacteria that use fibre as an energy source. These bacteria flourish and they can grow and populate our colon, producing beneficial by-products.” 

This community of microbes in the gut can be thought of like a rainforest. Understanding one bacterial species may be interesting, but it probably doesn’t give you the picture of the whole ecosystem. 

While individual species in the microbiome work together to create something larger than the sum of its parts, it isn’t always harmonious. When things go wrong, they can go very wrong. 

Gut trouble

C. difficile infection usually occurs after a course of antibiotics, and acts like a bad stomach bug. But unlike a stomach bug, once the bacteria has taken hold in the gut, it can be extremely hard to get rid of. 

One in six people who have a C. difficile infection will get a second infection in the next eight weeks, and another course of antibiotics only works in about a quarter of cases. 

Faecal transplants are more effective at treating these recurring infections, and have around a 90 per cent success rate. 

Poo transplants are showing promise in other areas too. 

Hannah Wardill, an oncology researcher at the University of Adelaide, is using FMTs to try and treat side effects of cancer therapy. 

“We know that most anti-cancer therapies are extremely damaging to the gut microbiome, and this is increasingly recognised as a driver of a number of symptoms and side effects of treatment,” she says. 

“Nausea, diarrhoea, infection; we’re even looking at the role of the gut microbiome in pain perception.”

Dr Wardill and her team recently published their first study looking at the use of FMTs in blood cancer patients, where they organised a transplant with the patient’s faeces collected before they started chemotherapy. Although the process went well, there were issues with collection. 

“These are people who have just been diagnosed, they’re starting therapy in maybe three or four days and we’re saying, ‘Oh, hey, can we collect your poo?’ It’s a difficult conversation to navigate, and it’s certainly not high on their list of priorities,” she says. 

Instead, Dr Wardill is now sourcing poo donated to stool banks by people like Mr Walker-Brown.

Stool banks are becoming more common around the world, with biotech companies as well as organisations such as the Red Cross in Perth taking donations in the past few years. 

But not all poo samples are created equal, and companies like Biomebank are trying to understand what turns someone’s poo from ordinary to super.

What makes a super pooper? 

Everyone who donates stool is screened for diseases and any other red flags. If those checks are passed, the poo will likely be effective when treated and used in a faecal transplant.

But some people have a microbiome that’s much more likely to lead to a successful transplant for C. difficile. These people are dubbed “super poopers“, and although they’re highly effective, researchers are still trying to understand why.

“We don’t yet understand those factors in their entirety,” Rob Bryant, an inflammatory bowel disease specialist and VP of Clinical Translation at Biomebank, says. 

“But we do know that super donors have a diverse microbiota — there’s a broader range of organisms. They have a consistent microbiota over time. And they have a nice, even spread [of microbial species].”

But using donated poo for transplants can be challenging.

Aside from convincing healthy people to donate in the first place, donor poo must go through intensive screening to avoid any unwanted bugs or bacteria. There is also the potential for contamination.

So biotech companies are trying to move on from using donors for their transplant material altogether by designing their own lab-grown super-pooper microbe mix. 

The search for the ultimate ‘poo’

For a place cultivating large amounts of gut bacteria, the lab room inside the Biomebank doesn’t smell as bad as you might think. Though according to research scientist Christopher Waterman, on some days “it smells like a fart”. 

His job is to grow individual strains of gut bacteria in specialised zero-oxygen conditions, and add them to a large library of bacteria. Dr Waterman tells me there’s four freezers worth of tiny sample vials — one of the largest, most diverse collections of human gut bacteria in the world.

They are trying to create their own “bacterial consortium” — a group of lab-grown, hand-picked bacteria — to use in the next generation of FMTs (or in this case, bacterial consortium transplants or BCTs).

With up to 54 per cent of our poo being bacteria and other microbes, the consortium product acts (and smells) like a poo-less poo. 

If the gut microbiome is the ecosystem equivalent of a rainforest, the team are collecting and growing each species of plant, animal and insect, and then trying to recreate the rainforest piece by piece.

“We’ve got an enormous library of microbes here, which we call our culture collection, that we can then select from,” Emily Tucker, an infectious diseases physician at Biomebank, says.

“Using learning from the literature and from our studies, we can then look at developing an ultimate microbiome for different diseases.”

This is still in the development phase at the moment, but small human and mice studies from around the world have shown it could be used for gut issues like inflammatory bowel disease.

According to Dr Tucker, the higher the percentage of bacteria you can add to the consortium (or what the team calls the “consortiome” — a play on “microbiome” and “consortium”) the higher the chance of resetting the gut effectively. This would change the gut microbiome from just a few bacteria dominating the colon to a wider variety of bacteria working in harmony.

Each lab-grown microbiome the researchers are working with has around 100 strains of bacteria — about 90 per cent of the known gene families from a healthy microbiome.

For now, the researchers are looking at using this for inflammatory bowel disease, but with a better understanding of the way the consortium ecosystem works, they may be able to design other microbiomes for different conditions.

The hope is that these could match or even exceed the results of the best poo donated today. 

Making a difference

Mr Walker-Brown doesn’t know how his poo rates compared to others that donate to the facility. 

“Apart from the guys being happy I come back, I don’t know the actual grades of the movements,” he says.

But donating to Biomebank has had some positive spin offs for Mr Walker-Brown. The team do a regular check up to make sure he’s healthy, and they have been providing him dietary advice on how to become more regular.

“Whatever goes in comes out. It makes you think a lot more about what you’re consuming.”

Most of all though, he’s just happy that his “natural” donations can make a difference. 

“As a winemaker, I love the idea of wild ferments and using microbes to make a healthy environment,” he says. 

“With your body, it’s the same. A complex set of microbes can make you a lot healthier.”