It’s an exciting time for microbiome research. There are implications for the use of FMT with colitis, IBS, obesity, depression, autism, cancer, and diabetes. This is the first in a series about the gut biome, also known as the microbiome and its impact on our health and well-being.
CASE STUDY
(I’ve added names to make it more interesting, you can read the full case study HERE.1 )
“I’ve been having diarrhea and terrible cramping since I finished my antibiotics,” Sally said with a grimace. She had returned to her primary physician’s office shortly after finishing a course of antibiotic treatment for bacterial vaginosis. The nurse took a thorough health history and discovered that Sally had been exposed to Clostridium difficile when visiting her aunt in the hospital. C. difficile infection (CDI) is the most frequent hospital-acquired infection in the US. It is a debilitating bacterial infection that strikes 500,000 Americans each year and kills 30,000. It is typically caused by antibiotics, which disrupt the normal intestinal flora, leading to an overgrowth of C. difficile bacteria in the colon.2
In an attempt to prevent a possible C. difficile infection (CDI), Sally was treated with a 14-day course of oral vancomycin, but the nausea and abdominal pain persisted.3 After doing a few tests, they discovered that Sally also had a Helicobacter pylori infection. The H. pylori was treated with triple therapy (amoxicillin, clarithromycin and a proton pump inhibitor.)
Three weeks later Sally was back in the office with escalating abdominal pain and diarrhea. A PCR assay was positive for CDI.4 Sally was referred to a gastroenterologist who prescribed a 12-week tapering course of oral vancomycin and started showing some improvement.
However, two weeks after finishing the vancomycin, diarrheal symptoms returned. Sally was then prescribed rifamaxin with Saccharomyces boulardii, a bacterium that has been found to be highly effective in treating CDI.5 She also underwent an esophagogastroduodenoscopy, which showed the H. pylori infection was still present as well.
Sally returned to her gastroenterologist after the rifamaxin and S. boulardii treatment had ended saying, “I’m still having diarrhea. I’m not sure how much more of this I can take. I haven’t been able to work and my FMLA is about to end.” She then burst into tears.
The nurse said, “It sounds like it’s been really hard for you. Would you like to hear about some other options?”
Sally nodded and blew her nose, “As long as it’s not more antibiotics.”
FECAL MICROBIOTA TRANSPLANT
The nurse said, “The doctor wants me to chat with you about fecal microbial transplant or FMT”
The nurse explained to Sally that FMT would involve the transfer of fecal material from a donor into Sally’s colon to restore the natural micro biotic environment.6
Sally made a face and said, “You want to put someone else’s….poop into me?”
The nurse said, “I know it sounds unusual, but it’s a well-accepted practice. Remember, CDI has an almost 7% mortality rate. It’s important to consider all your options. The cure rate for FMT is much higher than with antibiotics. You can have a family member donate the stool if they meet the criteria.” The nurse also shared with Sally that in some larger cities there are nonprofit stool banks (there’s a large one in Cambridge, Massachusetts for example).4
After some resistance, Sally finally agreed to the idea and chose her 16-year old daughter, Amanda to be the stool donor. Amanda was screened for suitability and met all the criteria. She had no health problems, no recent exposure to antibiotics, no recent tattooing or body piercing and no history of drug or alcohol use. She was negative for HIV, syphilis, viral hepatitis A, B & C, C. difficile, and Giardia lamblia. A routine stool culture was performed for enteric pathogens, which was also negative.
Prior to the FMT, Sally was treated for H. pylori with quadruple therapy (metronidazole, tetracycline, bismuth, and a proton pump inhibitor.) Sally stopped the antibiotic therapy two days before the procedure. On the day before the FMT, she was prescribed a liquid diet and an enema. Amanda took a laxative the night before to ensure a timely and adequate bowel movement. She collected her stool in a hat (a plastic basin that fits inside the toilet basin). As instructed, they suspended the stool in normal saline and used a disposable stick provided to break up the stool. Amanda and Sally then filtered the solution through a disposable coffee filter (This article from the NY Times has some great images if you want to see more of what FMT looks like).
Upon arrival at the outpatient clinic, Amanda handed the nurse a specimen container holding 600 mls of brown liquid. Sally was given Imodium to help her hold the donor stool for as long as possible. Sally was then sedated with IV sedatives and the FMT was performed by colonoscope. The colonoscope was advanced through the entire colon and then it was withdrawn, the donor stool was delivered into Sally’s terminal ilium.7
Sally was overjoyed with the results. At a 16 month follow up visit, she reported no further recurrence of C. Difficile after the Fecal Microbial Transplant.
POOP WARS
There’s a war raging in health care…okay, several, actually, but this battle pits drug companies against doctors and patient advocates over the use of human excrement. It’s a question of classification. Are the fecal microbiota that cure C. difficile infection a drug, or are they more like organs, tissues and blood products? The answer determines how the FDA regulates the procedure, how much it costs and who gets to profit. In 2013, the FDA began attempts to regulate FMT as a drug but said it would continue to study the matter before making a final decision. A change in regulation could result in increased costs for patients, as well as some of the exciting new therapies that are attempting to harness the microbiome to treat diseases from diabetes to cancer.
As this article is being published on allnurses.com, the FDA is nearing a final decision. You can find out more and weigh in at The Fecal Transplant Foundation (on facebook). The fear is that the FDA is favoring the interests of what Dr. Alexander Khorust, a gastroenterologist at the University of Minnesota calls the “poop drug cartel” – a group of companies seeing approval for new ways (think FOR PROFIT ways) to deliver the active ingredients in feces. He states, “An obscene amount of money is being thrown around by companies trying to profit off what nature made.”4
INSTANT COFFEE
It’s important to consider that alternate delivery of fecal material might be crucial to saving lives. FMT is a time-consuming process, requiring coordination of care for both donor and recipient. FMT also requires IV anesthesia, which isn’t an option for all patients. One of the new delivery methods involves freeze-drying the material and giving it to the patient in pill form are already in the works. According to Dr. Herbert DuPont, director of the Center for Infectious Diseases at the University of Texas, frozen and freeze-dried microbiota are as effective in treating C. difficile infections as “fresh material” The only difference in outcomes appears to be the speed at which the patient is cured. Fresh material improves bacterial diversity in about a week, compared to 30 days for lyophilized material. The biggest benefit is convenience. Dr. DuPont compares the pill that his team is testing to “instant coffee” because it’s stable and can be transported easily.2
THE FUTURE
The human body contains trillions of microorganisms. Humans are, by cell count, approximately 90% bacteria, with bacteria outnumbering human cells by 10 to 1. Because of their small size, however, microorganisms make up only about 1 to 3 percent of the body's mass (in a 200-pound adult, that’s 2 to 6 pounds of bacteria). Despite their small size, scientists are discovering they play a vital role in human health. Most of the research into the impact the microbiome has on health has occurred in the last five to ten years, and it is incredibly exciting.4
These trillions of organisms that colonize the body are increasingly being seen as critical for healthy brain development and immune function. Scientists have been inspired by the success of fecal transplants for CDI and are racing to develop similar treatments for an array of ailments like depression, obesity, autism, ulcerative colitis, Alzheimer’s and Parkinson’s diseases.4
My next article will revisit Sally and Amanda. Remember that Sally returned for a 16 month follow up visit with no signs or symptoms of C. diff, however, she now has another problem, a BMI of 33 (Sally’s weight before the FMT was stable at 136 pounds with a BMI of 26). “I’ve gained all this weight and I can’t seem to get it off. What’s happening to me?”
Stay tuned for more!
Read Part 2 - Using Bacteria to Control Your Weight
REFERENCES
- Alang, N. & Kelly, C. R. (2015). Weight gain after fecal microbiota transplantation. Open Forum Infectious Diseases, 2(1). Retrieved from: Oxford University Press
- New Fecal Transplant Method Treats C. difficile "Like Instant Coffee"
- Oral vancomycin prophylaxis is highly effective in preventing Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients.
- Drug Companies and Doctors Battle Over the Future of Fecal Transplants
- New advances in the treatment of Clostridium difficile infection (CDI)
- Fecal Transplantation (Bacteriotherapy)
- You Won’t Believe How This Works: Fecal Transplant
