THE BLOG

Repoopulating the Gut

03/07/2013 02:43 pm ET | Updated May 07, 2013

The story unfolding about Clostridium difficile (C. diff for short) infection is one I pay close attention to. Brenda Watson and I covered the topic of C. diff in our book The Road to Perfect Health. There is no effective treatment for recurrent C. diff infection, which puts this population at higher risk of complications, including death. In fact, it was recently announced that C. diff infection is now the ninth leading cause of gastrointestinal death, showing a 230 percent increase from 2002 to 2009. [1]

People with recurrent C. diff infection have been found to also have intestinal dysbiosis, or an imbalance of gut bacteria. [2] Yet the treatment of C. diff infection -- the antibiotic vancomycin -- induces dysbiosis itself. Not only that, but most C. diff infections are caused by antibiotic treatment. Scratching your head? You're not alone. It's a vicious cycle: Take antibiotics, get dysbiosis, get C. diff, treat C. diff with antibiotics, get dysbiosis, get C. diff again, get antibiotics again, etc. You can plainly see that this might not end well.

With no effective treatment in sight and the death rate of this condition rapidly increasing, drastic times called for drastic measures. Enter fecal bacteriotherapy, also known as fecal transplant, or the transplantation of stool from healthy donors. Case reports and studies of fecal transplant for recurrent C. difficile infection have reported an average success rate close to 90 percent. [3,4] That's an impressive number for such a difficult disease.

In a recent lecture published in the American Journal of Gastroenterology, gastroenterologist Lawrence J. Brandt, M.D., stated, "We are witnessing a paradigm shift in the way we understand health and treat disease and in its center is our microbiota." [5] (Microbiota is the term for our collective gut flora or microorganisms.) Brandt also believes fecal transplant will eventually replace antibiotics as treatment for C. diff infection. This would certainly make sense, given the involvement of dybsiosis in these patients.

Brandt goes on to mention the number of conditions outside the gut already being treated by fecal transplant therapy: Parkinson's disease, fibromyalgia, chronic fatigue syndrome, multiple sclerosis, myoclonus dystonia, obesity, insulin resistance, and the metabolic syndrome. Impressive list, and one that supports the relevance of the gut connection to health conditions outside the gut.

Although it may seem a new treatment, fecal transplantation has been around since the 4th century, used by a well-known traditional Chinese medicine doctor Ge Hong for the treatment of food poisoning or severe diarrhea. [6] But there is a major hurdle accompanying fecal transplant therapy, despite its impressive success rate: the yuck factor.

Many physicians and patients alike are not particularly interested in administering or receiving a fecal transplant, unless they have reached the end of their rope, so to speak. Administration is cumbersome, potential of transmitting infection cannot be ruled out, and there is a lack of efficacy data from randomized, controlled trials. [7] That's unfortunate, given the potential benefit, but researchers are working out a way around this. In a recent study published in the new journal Microbiome, researchers harvested beneficial bacteria from the stool of a healthy donor, and then purified, isolated, identified, and tested the mixture, which they aptly named RePOOPulate. [8]

The RePOOPulate mixture contains 33 species of commensal and beneficial bacteria, and was administered at 350 billion CFU in 100 mL of water into the colons of two people with recurrent C. difficile infection unsuccessfully treated with antibiotics. Both patients reverted back to their normal bowel pattern within two to three days and remained symptom-free for up to six months (the length of the study). The researchers concluded, "This proof-of-principle study demonstrates that a stool substitute mixture comprising a multi-species community of bacteria is capable of curing antibiotic-resistant C. difficile colitis."

In the report, they highlight the importance of a multi-species mixture to the success of the treatment:

These data suggest that a multi-species derivative community such as that used here will be more generally useful than a single organism probiotic or a mixed culture of such probiotic species, because the microbes in RePOOPulate are derived from a community and probably retain some community structure that enables them to colonize the appropriate environment.

They found that the bacteria in the RePOOPulate mixture were still present in the patients up to six months after receiving it, showing that the bacteria were able to successfully colonize the gut and remain there long term.

The RePOOPulate study is going right where I knew we were headed -- to the creation of a super probiotic that contains a diverse array of beneficial bacteria that most resemble the bacteria present in the healthy human digestive tract. Multi-strain probiotics at high dosages are the closest thing we have to the real thing, but without the yuck factor.

Personally, I think it should be considered malpractice to not administer probiotics along with antibiotics when treating C. difficile infection, based on what we understand of this condition. Fortunately, we are getting closer and closer to the perfect probiotic for that purpose.

References:

1. A.F. Peery, et al., "Burden of gastrointestinal disease in the United States: 2012 update." Gastroenterology 2012 Nov; 143:1179.

2. J.Y. Chang, et al., "Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea." J Infect Dis. 2008 Feb 1;197(3):435-8.

3. M.J. Hamilton, et al., "Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection." Am J Gastroenterol. 2012 May; 107:761.

4. T.D. Lawley, et al., "Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice." PLoS Pathogens. 2012 October;8(10):e1002995.

5. L.J. Brandt, "American Journal of Gastroenterology Lecture: Intestinal microbiota and the role of fecal microbiota transplant (FMT) in treatment of C. difficile infection." Am J Gastroenterol. 2013 ;108:177-85.

6. F. Zhang, et al., "Should we standardize the 1700-year-old fecal microbiota transplantation?" Am J Gastroenterol. 2012;107:1755.

7. C.P. Kelly, "Fecal microbiota transplantation--an old therapy comes of age." N Engl J Med. 2013 Jan 31;368(5):474-5.

8. E.O. Petrof, et al., "Stool substitute transplant therapy for the eradication of Clostridium difficile infection: 'PePOOPulating' the gut." Microbiome. 2013;1:3.

Dr. Leonard Smith is a prominent board-certified, general, gastrointestinal and vascular surgeon who had a successful private practice for 25 years. In addition to his active surgery practice, he also incorporated lifestyle, diet, supplementation, exercise, detoxification, and stress management into many of the therapies he would prescribe. Many of his patients with cancer, cardiovascular disease, and other serious illnesses did so well under his treatment regimes that he began to devote most of his career to foundational health care and preventive medicine.

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