Friday, August 19, 2011
Fecal transplants: rethinking therapy for tummy troubles
Since Alexander Fleming first discovered penicillin in 1928 and the first sulfonamide antibiotic was introduced in 1932, medical science has created countless chemicals that inhibit the growth of disease causing microbes. Dirty wounds that would have resulted in certain death prior to antibiotic therapy were treatable and curable. It must have been a very exciting time to be a doctor.
In my lifetime, the number of antibiotics available to use to treat infections has grown to the extent that, even with constant vigilance, I can't keep track of them all. Antibiotics are more often prescribed not for life threatening infections, but for treatment of symptoms such as sore throats, stuffy noses and inflamed bug bites for which those antibiotics are undoubtedly not effective, symptoms which if left untreated would resolve on their own. These prescribed antibiotics kill bacteria anywhere in the human body where the blood delivers them, hitting complex bacterial communities much as a bombing raid might hit our home towns. Appreciation for the beneficial roles of these communities, or microbiomes, is increasing in scientific and medical circles, but indiscriminate use of powerful antibiotics continues to be common practice.
Of the many problems associated with use of antibiotics, resistant bacteria is one of the most commonly recognized. In the hospital setting a common scenario is development of severe diarrhea following antibiotic use, often leading to prolonged hospital stays, nutritional compromise and sometimes death. The usual cause of this diarrhea is the bacterium Clostridium Difficile. At worst, this bacteria, which is resistant to many common antibiotics and common in the human gut, will cause diarrhea, nausea and vomiting, abdominal pain, fever and a raw intestinal lining that can even perforate, releasing stool into the sterile abdominal cavity. There are two antibiotics that can attack Clostridium Difficile, but even at their most effective they can still leave viable bacteria which can multiply again, causing recurrent or chronic infection.
For more than half a century physicians have recognized that, since C. Diff occurs after the healthy bacterial population in the gut is devastated by antibiotics, that restoration of the good bacteria might lead to a cure. In 1958 a physician reported using an enema of stool from a healthy donor to cure this disease. More recently we have attempted to treat persistent cases with "probiotics"--supplements consisting of bacteria like those in yogurt, and another, similar to one used in making fermented spirits, Saccharomyces Boulardii. These tricks have sometimes worked, though not, by any means, infallibly. It is tempting to try to treat a disease like C. Diff with a bacteria that smells good and is encased in a gel cap, one which is well defined and undeniably safe. Nevertheless, it makes much more sense that a persistent and pernicious pathogen would be vanquished by an army of cooperating bacterial species, no matter how smelly and undefined they are. Thus fecal transplantation has started to find its way into standard medical care.
In our small office my gastroenterology colleague was treating a very miserable elderly woman with recurrent and persistent C. Diff diarrhea. He had used all the appropriate antibiotics to treat it, all of the sweet smelling probiotics available, and still she cramped, she pooped, she had no appetite, she felt terrible. In fact, she was slowly dying. He recommended fecal transplant (also known as fecal flora reconstitution or fecal biotherapy.) She was game.
This is how it was done: The donor, usually a household or family member, donated the first morning bowel movement. The donor should be tested for parasites and blood diseases and is screened to make sure she or he has normal bowel habits. The recipient cleaned herself out by drinking the solution that we use prior to a colonoscopy, about a half a gallon of flavored polyethylene glycol solution. In a blender (which was subsequently thrown away) the BM was mixed with saline solution (not bacteriostatic) and then delivered in several portions as a retention enema. That's all.
Our patient was cured, just about immediately and so far completely. This is a very common result, according to the studies I have been reading.
Other techniques include instilling the solution by fiberoptic scope and by a plastic tube that goes through the nose and into the small intestine. There is no indication as to which technique works best.
At least one study also noted success in treating ulcerative colitis, a chronic inflammation of the bowel, with fecal transplant. It is far from standard treatment for this condition, however.
One of the most common bowel problems in my practice, leading to significant disability and work loss, is something called Irritable Bowel Syndrome (IBS). This condition causes no inflammation of the colon, just diarrhea and constipation, bloating, cramping and sometimes a sensation of incomplete emptying. Treatment of this condition usually involves avoiding foods that make it worse, bulking up the stool with fiber and occasionally taking medications that reduce bowel motility and cramping. Lately we have found that certain antibiotics sometimes reduce the associated bloating and discovered that the disease often follows a case of traveler's diarrhea, suggesting a bacterial cause. We have begun to treat irritable bowel with probiotic pills with some success. Is it not, perhaps, time to introduce healthy stool into patients with irritable bowel and look for cure rather than remediation?
Studies on obese humans and mice suggest that the bacteria in the gut is different than in their normal weight counterparts. In the case of mice, transplantation of bacteria from obese to normal weight animal results in weight gain. Are we, in fact, attributing fault regarding weight maintenance to human will power, when that fault at least partly belongs to our internal flora?
Another bacterial community that is vulnerable to decimation by antibiotic use is the vagina. It is very common for my patients to develop an itchy yeast infection after use of any of the powerful antibiotics that I prescribe for urinary tract and other infections. I treat these with oral or topical antifungal medications to wipe out the yeast, but it is not unusual for a patient to continue to itch on and off for weeks even after treatment. Often we recommend use of healthy bacteria, such as found in yogurt, to improve the flora. We usually have our patients eat the yogurt, but sometimes recommend they use it inside the vagina. It seems more likely that reconstitution of a whole community of bacterial flora by way of a transplant from a healthy vagina would work considerably better.
I sense at least 50% of my readers may be stifling a gag reflex at this point, assuming that they have made it this far. I sympathize, and yet it hardly seems reasonable that squeamishness should be an important decision rule in determining good therapy.
Certainly these thoughts and trends are part of a very important thought shift in organized medicine. They represent an element of respect for the complexity of the human organism and recognition of the limitations of our use of the chemicals of pharmacology to treat disease. The tremendously complex and interactive community that we know as our own bodies deserves to be recognized as we move in the direction of improving the quality of health care.