The last thing you might expect to greet your senses when you enter an art gallery is the pungent smell of feces. But that’s exactly what artgoers experienced when encountering conceptual artist Wim Delvoye’s exhibit, “Cloaca” in 2000. Cloaca is a digestive machine of impressive design; it was nearly a decade in the making, involving extensive consultation with gastroenterologists, computer scientists, and engineers. A series of pipes, tubes, and pumps transport food through a mechanical grinder and into a series of large glass vats bearing digestive enzymes and bacteria. Over the course of 27 hours and over 30 feet, the product is ultimately extruded onto a conveyer belt as feces. Cloaca makes a subversive statement on the pointlessness of modern life; to Delvoye, a machine that could be so expertly constructed to produce something as worthless as excrement was the pinnacle of uselessness.
As it turns out, such a machine might not be so useless after all. Or, more specifically, it’s fecal output may not be such a useless product. By weight, 60% of feces is made up of bacteria. In our gut there are more than 100 trillion bacteria, representing over 1000 species. These bacteria play a vital role for us: they aid in digestion, nutrient absorption, help develop immune responses, and they actually protect us from pathogens. Together, these groups of commensal bacteria form an intricate community collectively called the gut microbiome, or gut microbiota. Like any complex ecosystem, however, minor perturbations can have profound effects on the whole, leading to imbalances among the different types of bacteria. This condition, termed microbial dysbiosis, is believed to play a key role in certain diseases of the gut.
Robogut, the brainchild of Dr. Emma Allen-Vercoe of McMaster University, is a bioreactor designed to mimic the complex conditions of the large intestine. Through Robogut, Dr. Allen-Vercoe has been able to develop a synthetic stool substitute containing specific types of bacteria found in human stool samples. Cloaca and Robogut certainly bear some similarities in their design. Both machines mirror the incredible complexity of our digestive systems, from the enzymatic and bacterial components, to the specific temperature, pH and anaerobic conditions found in the gut. As well, both machines produce an unmistakable odour that cannot be masked. But the intent behind these two machines couldn’t be more different. While Delvoye’s machine is a statement of pointlessness, Robogut explores the potential of our gut bacteria as a treatment for patients with severe infections caused by Clostridium difficile.
In healthy people, the spore-forming bacteria C. difficile, also known as C. diff, does not pose a significant health risk. For those with weakened immune systems and the elderly however, C. diff can be a serious health concern. C. diff has emerged as the most common cause of infectious diarrhea in hospitals and long-term health care facilities in developed countries, including Canada. Infection occurs when the bacterial spores, which are found in feces and on fecal-contaminated surfaces, are accidentally ingested. Because C. diff spores are long-lived and resistant to routine cleaning procedures, they are readily transmitted between beds and rooms in health care settings. Once these highly resistant spores germinate and establish in the colon,C. diff bacteria produce inflammation-inducing toxins that can cause disease. Symptoms include watery diarrhea, abdominal pain, fever, and potentially life-threatening complications; an exceptionally virulent outbreak in Quebec in 2004 resulted in the death of over 1000 hospital patients.
C. diff follows what clinicians refer to as the 20-40-60 rule: contracting C. diff once renders a person 20% more likely to get the infection a second time. With each subsequent recurring infection, the risk increases to 40% and 60%, and symptoms become increasingly severe. Patients are typically treated with specific antibiotics, but those patients with recurring infections usually find that once the round of antibiotics are complete, the infection returns. Researchers believe that recurring infections are indicative that microbial imbalances are never properly restored, allowing C. diff to easily establish itself again. Indeed, inducing microbial imbalances through the prolonged use of certain antibiotics has been implicated as a risk factor for contracting an initial infection, as some antibiotics can wipe out good bacteria, giving C. diffthe opportunity to colonize the intestine.
The cost of antibiotic treatment is staggering, especially given the likelihood of recurrent infections. This is to say nothing of the emotional and physical pain facing patients living withC. diff infections. Estimates suggest that in 2012, there were over 37,000 cases of C. diff in Canada, with a socio-economic price-tag of over 280 million dollars. Management of this disease has proven exceptionally challenging for physicians, as current treatments are falling short. Therapies with long-lasting effects are needed, and researchers believe that requires the restoration of microbial balance in the gut. But how can you get back the good bacteria, to keep the bad ones at bay?
The use of fecal microbiota transplant as a therapy was first reported in the scientific literature in 1958. Sporadic case reports involving this curious therapy were published since then, but it was not until 2011 that a group of researchers at McGill University in Quebec, led by Dr. Amee Manges, published a systematic review in Clinical Infectious Diseases that examined all known case reports involving this type of therapy. The study included a total of 27 previously published case reports involving over 300 patients with recurring C. diff infections. Dr. Manges reported that in an astonishing 92% of cases, patients receiving fecal transplants had resolution of disease. The need for properly controlled trials that compared the effects of fecal transplant therapy with standard antibiotic treatment were clearly needed.
In 2013, the first randomly controlled trial was published in the New England Journal of Medicine by a group of researchers from the Netherlands and Finland, led by Dr. Josbert Keller. Feces were collected from multiple donors, diluted and strained, and a single fecal infusion was delivered to one group of patients with recurring C. diff infections, while a second group received the standard antibiotic treatment. Ten weeks later, physicians unaware of treatment groups assessed the patients for disease. They reported that 94% of the patients receiving fecal microbiota transplants -including two patients that required a second infusion of feces- were cured. Less that one third (31%) of the patients that received standard antibiotic treatment had resolution of their disease.
Recently, as reported in Microbiome in 2013, the synthetic stool produced by Dr. Allen-Vercoe’s Robogut was tested in two patients with recurring C. diff, and both patients were cured. Moreover, the researchers confirmed their hypothesis: that synthetic stool treatment resulted in an altered microbiome in patients that was maintained even 6 months after initial treatment. This technology paves the way for the production of reproducible batches of microbiota, and the identification of which bacteria, or which combination of bacteria, can restore microbial balance in the gut.
Delvoye used his synthetic digestive machine to explore the futility of the human condition. But futility, it seems, is a matter of perspective; Robogut’s synthetic stool explores the utility of gut bacteria as a treatment. While the synthetic production of poop likely appears a worthless enterprise to most of the population, Robogut’s output represents liquid gold to scientists, generating species of bacteria that have never before been cultured in a lab. The potential benefits of these bacteria are not limited to recurring C. diff infections; researchers see hope for treatment in a wide range of gut diseases including ulcerative colitis, Crohn’s disease, and irritable bowel syndrome. And to the millions of people that suffer such chronic diseases, such an endeavor is anything but futile.