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In 1961, the late Italian artist, Piero Manzoni became world famous for canning 90 times 30 grams of his own excrement in 90 tins labelled in four languages as: “Artist’s Shit”. Each tin was sold for the price of 30 grams of gold and sparked debate on the value of art.

At the time, no one could have imagined that the content of each tin was actually worth its weight in gold. Or more, since faeces save lives.

Nowadays, people with Clostridium difficile, a potentially fatal intestinal infection, are successfully treated with Faecal Microbiota Transplantation (FMT). Increasingly, researchers are investigating whether other diseases can also be treated with faeces from healthy donors.

One such researcher is Kenneth Klingenberg Barfod, associate professor of microbiology at the Department of Food Science, University of Copenhagen (UCPH FOOD).

He is investigating whether pills containing donor stool can restore the gut microbiome in people struggling to recover from anorexia nervosa (AN).

At the time of writing, he is finalising a pilot study in which 18 volunteers each took 24 capsules containing faeces, washed down with juice, all in the space of an hour. And the results are promising.

“We can see that after just one week, there’s an effect on the microbiome in the hoped-for direction,” he says.

A life-threatening mental illness

AN is a highly complex eating disorder that mainly afflicts teenage girls and young women. They have a distorted body image, limit their food intake for fear of weight gain, and the result is life-threatening low body weight accompanied by physical and mental disorders.

Of all mental illnesses, AN is the hardest to cure and has the highest mortality rate. The rate is three times higher than in the general population, with some patients dying from malnutrition and others from suicide.

“This group of patients doesn’t have a lot going for it. There are no large-scale clinical studies, no medicines in prospect, and there have been no therapeutic breakthroughs in the past 60 years,” says Barfod.

Despite that, he struggled to secure funding for his research.

“Faeces are difficult to patent and turn a profit from. And although research into the gut microbiome is rocketing, the downside for AN is that most of the focus is on obesity research.”

For this reason, he was thrilled to be granted funding from the Lundbeck Foundation for the pilot study he is now finalising.

“The project was a good fit for the Foundation’s LF Experiment grant because this programme favours ‘way-out ideas’ that don’t align with other funding sources,” he says.

The idea came to him ten years ago when he was long-listing diseases that might conceivably be linked to the gut microbiome. Anorexia nervosa came top of the list.

Starvation compromises beneficial bacteria

Barfod’s interest in the gut microbiome followed on naturally from his decision to study biology.

“My angle is evolutionary biology. I’ve always been fascinated by how humans evolved with these microbes and the role they played in early-stage pathogenesis,” he explains.

Research in the microbiome has rocketed in the last 15 years, mainstreaming an awareness that we are never alone: hosting billions of bacteria, viruses and fungi on and in our bodies. Bacteria alone account for about a pound of our body weight.

Science has firmly established that the gut microbiome communicates with all of the organs in our body, helping to regulate our appetite and thereby our weight by means of dynamic gut-brain communication via nerves, signalling substances and the immune system. The microbiome also regulates nutrient uptake from food.

Several studies have shown that individuals with AN have a less diverse microbiome than healthy individuals. This was recently demonstrated by a major Danish study published in Nature in 2023.

“Obviously, if you starve yourself, you’ll be starving the microbes, too. In some individuals, the microbiome is re-established once their eating normalises, but that’s not the case for everyone. So, my hypothesis is that the gut microbiome in people with AN has been chronically altered. That means that even if they try to eat normally, they’re locked into the illness”, says Barfod.

He likes to compare the gut microbiome with other ecosystems such as a rainforest, desert or ocean.

“The gut is one gigantic ecosystem, so there’s a big difference in which microbes inhabit different parts of the gut. Imagine a single bacterium in a trough in the gut surface. There are five or six troughs per millimetre, but for the bacterium the distance to the next trough is equivalent to six kilometres for a human.” Although microscopic, the gut microbiota make up a vast and complex universe.

Multidisciplinarity in play

Until now, microbiome research has been concentrated on the types of bacteria found in the gut. But Barfod believes that main focus should be on the function of those bacteria.

“For the ecosystem, function matters most. Some bacteria, for example, ingest mucus and stimulate further production of protective gut mucus. However, that’s not to say that this type of bacteria is indispensable. Different bacteria can have the same function, so it’s only when we lose a function altogether that the ecosystem suffers.”

While Barfod is on home ground with ecosystems, familiarising himself with anorexia nervosa put him on a steep learning curve. He collaborates with researchers from other disciplines like medicine and bioinformatics.

“In biology, we have tools and a terminology to describe what makes up an ecosystem, how it can collapse, and what can be done to restore it. That’s what I bring to the field. But if the aim is to open new doors, things don’t really start moving until people from different scientific disciplines sit down to discuss the same problem,” he explains.

These days, Barfod knows more than most experts about the link between gut bacteria and AN, but his focus is on making a difference for anorexia patients.

“If the conclusion is that we’re able to help just a fraction of the patients, then we’ll be pioneering a whole new therapy, and one that is straightforward and virtually risk-free, too.”

Through the pilot study Barfod has demonstrated the feasibility of recruiting participants for a trial of FMT, even if some volunteers with AN suffer from food aversion and germophobia.

He has also shown that the study is viable in purely practical terms, and that it potentially benefits patients.

The next step is a clinical study to determine if AN patients are able to gain weight after repeated FMT therapy using donor stool from healthy young women of normal weight.

So far, Barfod does not have the funding in place, but he hopes that the great interest in research into the gut microbiome and mental health disorders in the young will help him secure the DKK 10 million needed to fund the study.

“The initial aim is to reach the point where FMT is recognised as one of the options for treating this eating disorder. So that’s what we’re working towards.”

The long-term aim is an established FMT therapy for anorexia.

Since the 90 tins of the artist’s excrement caused a stir in 1961, the idea that faeces are worthless has undergone a sea of change. Today, Denmark has stool donors and other countries have established stool banks. And we are most likely set to see even more FMT therapies in the future.

Aside from AN, potential candidates for FMT therapy include other eating disorders and mental illnesses as well as arthritis, childhood asthma and diabetes. And looking to the future, American researchers tell us the young will be “banking” their healthy faeces so that in later life they can restore a healthy gut microbiome using their own bacteria and in so doing live longer free from disease.