Poop Pills: Fecal microbial transplant offers a promising treatment for obesity

What do the Bedouins, elephants, modern medicine and 16th century Chinese physician and herbalist, Li Shizhen, have in common? They all believe in the medical value of coprophagia—that is, stool consumption.

While to modern sensibilities eating poop seems, to put it kindly, unsanitary, it is in fact a practice with a long and rich history. Many animals practice coprophagia. Because newborn elephants, koalas, hippos and giant pandas are born with no bacteria in their stomachs, they must eat the scats of their mothers or some other adult animal in order to populate their guts with the necessary bacteria for digestion. The practice is able to establish very necessary intestinal function.

In humans, the first written records of coprophagia were found in China—during the Dong-kin dynasty in the 4th Century, human feces were used to treat food poisoning. Li Shizhen, in his famous 16th-century book on Chinese traditional medicine Ben Cao Gang Mu, carefully listed recipes for a “yellow soup,” a suspension formed from fresh, dried, or fermented fecal matter that yielded miraculous results as a cure for abdominal diseases such as constipation, diarrhea, pain and vomiting. Moreover, the Bedouins, a tribe of seminomadic Arabs, have long touted fresh camel feces as a treatment for bacterial dysentery, and German soldiers serving in Africa during World War II confirmed the treatment’s efficacy. Now, in a continuation of a centuries-long medical practice, modern medicine is looking to fecal matter as a treatment for obesity.

The procedure has existed for some time, and is known as a fecal microbial transplant, or FMT. The basis of FMT lies in gastrointestinal bacteria. Everyone has millions of bacteria in, around and on them; in fact, in every human there are about ten times as many bacterial cells as there are human cells. These bacteria are essential to normal bodily function, and nowhere are they more important than in the gut, where they aid in digestion and interact with different bodily systems.

Although their role is not yet entirely understood, recent studies suggest these bacteria affect immune function and energy metabolism. An imbalance, therefore, leads to a predisposition to diseases such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), or recurrent Clostridium difficile infection (RCDI). In a fecal microbial transplant, fecal matter from a healthy individual, which also contains bacteria from a healthy intestine, is introduced into the ailing system to revive and diversify the bacterial colonies. As many ancient societies discovered, this is a remarkably effective treatment with no serious side effects ever reported.

FMT has been long established in veterinary medicine, where it has been employed for over a hundred years in various capacities. Most regularly, newborn animals are often given feed with stool additives to promote intestinal health. Even for humans, fecal microbial transplant has been an accepted procedure in Western medicine for decades. The Chief of Surgery at Denver General Hospital, Dr. Ben Eiseman, first reintroduced it in a scientific context in 1958. Dr. Eiseman and his team were treating four patients diagnosed with pseudomembraneous colitis, an extremely painful and even potentially fatal inflammation of the colon. In his paper published in the Journal of Clinical Gastroenterology [4], Eiseman et. al. demonstrated astonishingly positive results when these four patients were treated with a fecal enema containing feces from a healthy human colon. All four patients made a full recovery.

Since that paper, the root cause of pseudomembraneous colitis has been discovered to be the bacteria Clostridium difficile. Once it was discovered to be bacterial in nature, the first line of treatment became something more standard; C. difficile infection is now mainly treated by the antibiotics metronidazole and vancomycin, with Dr. Eiseman’s fecal microbial transplant reserved as a last resort. However, antibiotics are not the ideal treatment. C. difficile thrives in an environment where the local healthy population is weak, so patients treated with antibiotics have a relatively high rate of recurrence. Although FMT has had difficulty becoming mainstream, in part due to its unusual nature, federal regulation is shifting to allow this extremely effective treatment to become available to more people.

The United States Food and Drug Administration decided to regulate human fecal matter as an Investigational New Drug, or IND, in late spring of 2013, a decision that meant fewer than 20 doctors in the nation were able to administer the treatment. Due to heavy opposition from both health care providers and their patients, that regulation was changed in June of the same year, allowing doctors to perform FMT, given thoroughly screened donors—although strictly for recurrent cases of Clostridium difficile. FMT, in this application, has been shown to have a success rate of upwards of 90%, with these patients having no recurring infections. However, despite the extraordinary efficacy of the treatment, it is still not widely available. Many patients have never heard of fecal microbial transplant, and more do not have a readily available donor who passes the rigorous health screening.

Although human stool is a difficult drug to regulate, research and projects are underway to make FMT a more plausible solution. In 2013, OpenBiome opened as the first stool bank in the United States, a centralized location to make safe stool more affordable and more easily transportable. In parallel with increasing efforts to make FMT a reasonable procedure, research has progressed to explore additional applications of the treatment.

The next step on this journey into the medicinal value of FMT is taking place in Massachusetts General Hospital, where clinical researcher Dr. Elaine Yu is administering a clinical trial to test the effects of fecal microbial transplants on obesity. In an on-going 24 week trial, obese patients are randomized, with a 50% chance of receiving either pills of freeze-dried fecal matter from healthy-weight individuals or placebo pills. Over the course of the trial, the patients’ weight will be tracked to observe the effect of obesity. Furthermore, their insulin resistance and their changes in lean and fat mass composition will be tracked. Other than the administered pills, the patients will be expected to continue their normal lifestyles, with no change to diet or exercise regimen.

Although the results of the trial are as yet unknown, the indicators are promising. At the UNIGE Faculty of Medicine, studies have found that obese and lean people have distinctly different microbiota, each with a specific composition. Although this fact alone does not establish a causal relationship, preliminary studies on mice demonstrate that when mice born in a sterile environment received microbiota from the obese, they tended to develop characteristics of obesity. There is therefore the possibility that with a fecal microbial transplant, healthy microbiota could displace the bacteria associated with obesity and insulin resistance and restore the patient to better health with no more than a freeze-dried poop pill.

With obesity a threatening epidemic in the United States, this new understanding of what causes and what can treat the disorder may be game changing. If this trial proves successful, this will change our understanding of metabolic disorders, and what can and cannot be altered in our bodies. However, whether or not this trial provides the miracle cure we hope for, it will provide invaluable insight into the mystery of our stool and the power of our stomachs.

Sarah Wagner is a freshman in Pierson College. Contact her at sarah.wagner@yale.edu.

(Featured Image courtesy of https://en.wikipedia.org/wiki/Fecal_bacteriotherapy#/media/File:E_coli_at_10000x,_original.jpg)

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