Your gut flora is a highly diverse ecosystem whose composition is as unique as your fingerprint. The more diverse it is, the healthier you are. Your gut ecosystem is also delicately balanced between many friendly symbiotes and a limited number of potentially harmful pathogens that are prevented from gaining a foothold and triggering an aggressive immune response.
There are times, however, when your gut’s garden gets out of balance, resulting in an overabundance of pathogens and/or a deficiency of beneficial bacteria. This is called dysbiosis — a state of microbial imbalance related to your gut ecosystem, your skin, your inner ear, or any of the other communities of microbes in your body. The scientific literature is quite robust in connecting dysbiosis of human ecosystems to adverse health outcomes. Science is linking dysbiosis to obesity and diabetes (aka diabesity), and there are abundant data in mice showing how lean mice can become fat through stool transplants from fat mice.
Scientists at the Center for Genome Science and Systems Biology at Washington University in St. Louis asked themselves a simple question: Does gut flora influence weight gain? To find the answer, they designed an interesting experiment. They took two groups of mice whose digestive tracts had been sterilized. In the first group, they colonized the mice’s intestines with flora from an obese cage mate. In the second group, they colonized the intestines with flora from a lean mouse. They then fed these two groups of mice the same diet for 2 weeks. At the end of 2 weeks, the mice that were inoculated with the obese microbiome had gained more weight than the mice exposed to the lean mouse’s gut microbiome, despite equivalent food intake and activity. (Turnbaugh PJ, Backhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3(4):213-23.)
This experiment shows that there are specific types of gut flora that cause you to gain fat—and other types that lead to weight loss. The type that’s dominant will dictate how much fat you accumulate. Many scientists term this “infectobesity”. This finding has led to an explosion of research which clearly links a dysbiotic gut flora to aberrant metabolic consequences such as diabesity.
A very interesting research findings was published in the journal Science. A study led by Dr. Jeffrey Gordon from Washington University showed that mice when fed microbes from obese people tended to gain weight but microbes from lean people protected mice from excessive weight gain-even when fed a high-fat low fiber diet that we call “The Standard American Diet” or SAD Diet”. In another “housing” experiment, lean mice were found to transfect obese mice with their healthy microbiota — “converting” the obese microbiome to a lean one which led to weight loss. But here is the catch. In order for this to happen the obese mice had to be eating a high fiber low saturated fat diet to help support the colonization of the healthy microbes form the lean mice. These findings were published in Science September 6, 2013;vol 341:6150.
There have been interesting preliminary human trials using fecal bacteriotherapy (FBT) — the transfer of intestinal flora from one individual to another to establish a healthy gut microbiome in the recipient. In other words, these “poo transplants” take the feces of someone with a healthy microbiome and introduce it into someone who lacks one.
Most of the FBT studies so far have been conducted to determine whether this intervention would be an effective way to fight recurrent Clostridium difficile infection (CDI) which is usually seen after the use of antibiotics. Once successfully treated with antibiotics, CDI has a high recurrence (>25%) since these antimicrobials generate dysbiosis that is characterized by a reduced diversity of the microbiota which favors the growth of pathogenic species. CDI is a highly contagious diarrheal illness that is increasingly common in hospitals and can be lethal. Of the more than 400 cases of recurrent CDI that have been treated with FBT so far, the cure rate is over 90 percent for those with a potentially life-threatening infection that that is resistant to all other aggressive medical therapy. This is a powerful model for showing how dangerous dysbiosis can be and how rebalancing the gut ecosystem by infusing a healthy mix of gut microbes can produce dramatic results.
The million-dollar question: Are poo transplants an effective intervention for weight problems? Though they’re not a cure for obesity, they appear to be capable of shifting one toward a lean metabolism. In 2010, a double-blind randomized controlled trial on the use of FBT for diabetes and obesity was conducted in 18 male subjects. Half received fecal material from lean male donors; half were implanted with their own feces. After 6 weeks, those who received fecal transplants from lean donors saw a marked reduction in fasting triglyceride levels and significant improvement in insulin sensitivity. (Vrieze A, Holleman F, Zoetendal EG, de Vos WM, Hoekstra JB, Nieuwdorp M. The environment within: how gut microbiota may influence metabolism and body composition. Diabetologia. 2010;53(4):606-13. El-Matary W, Simpson R, Ricketts-Burns N.). This is a small test group, but the results were replicated in a similar follow-up study by the same researchers, so the science is promising.
Does that mean you’ll be able to walk into your doctor’s office in the near future and ask for a poo transplant to improve diabetes or lose weight? Not likely. The safety of fecal transplantation has never been formally investigated long term, and clinicians have expressed concerns about FBT “opening up a can of worms” after 4 of 77 patients developed a de novo autoimmune disease after FBT. (Fecal microbiota transplantation: are we opening a can of worms? Gastroenterology. 2012;143(2):e19; author reply e-20.) Furthermore, the FDA limited the practice of FBT to those with CDI-associated diarrhea that failed conventional medical therapy provided donors are properly screened and patients are informed that fecal transplants are still experimental.
This is an exciting area of research. The Johns Hopkins University School of Medicine and its dean, Dr. Paul Rothman, have formed a microbiome interest group led by Drs. Cynthia Sears and Glenn Treisman to set priorities and to collaborate and pool resources. I’m fortunate to be working with this distinguished team of investigators. Dr. Linda A. Lee, leads the Johns Hopkins FBT program. Dr. Lee is a pioneer and leader in the field of integrative gastroenterology and director of The Johns Hopkins Integrative Medicine & Digestive Center and is Clinical Director for the Division of Gastroenterology at Johns Hopkins Hospital.
Research on FBT may pave the way for more targeted, safer interventions for obesity, irritable bowel syndrome, inflammatory bowel problems, metabolic syndrome, and more.
To your good health.
Dr. Gerry Mullin