Fecal Transplant and Inflammatory Bowel Disease

By Dr. Brian Bressler

In the past few years, interest in a potential new therapy for the treatment of gastrointestinal (GI) infections and inflammatory bowel disease (IBD) has grown rapidly. It involves the transplantation of stool from a healthy donor to the colon of a sick person. In theory, it works by quickly reestablishing healthy communities of “friendly” bacteria in the colon. Known as fecal transplantation, this unconventional therapy is neither approved, nor standardized, to date. But it shows promise in certain instances. Research is ongoing.

It’s quickly gaining acceptance, for example, as the “most effective therapy” for relapsing Clostridium difficile infection. There is even some suggestion that it may be used in place of aggressively prescribed antibiotics as front-line therapy against this epidemic infection. Clostridium difficile infection is a leading cause of hospital-associated gastrointestinal illness.

Inflammatory Bowel Disease is comprised of Crohn’s disease and ulcerative colitis. These conditions are characterized by inflammation of the gastrointestinal (GI) tract. While Crohn's and colitis are clinically distinct entities, they share many similarities. Not least among them is the association between the diverse communities of bacteria living within the GI tract and the disease processes involved in IBD. Scientists are still unraveling the connections among gut microbes and IBD. The research is intriguing and promising.

The New Era of Metagenomics

Relatively recent advances in medical technology and computing have allowed scientists to identify and catalog the huge numbers of microorganisms living in the GI tract with unprecedented ease and precision. In the past, our knowledge of this vast collection of microbial communities—now referred to as the microbiome—was akin to the knowledge that can be gleaned about an enormous chunk of submerged ice by observing its floating tip.

We had some limited knowledge of which species were dwelling where, and in what numbers. But the vast majority of these microbes remained as mysterious as the submerged ice of an iceberg. Many had never been identified before.

However, a new technology known as metagenomic sequencing is allowing scientists to explore the microbiome as never before. It’s transforming our understanding of the role played by these diverse organisms. In short, it’s becoming increasingly clear that the health and diversity of the microbial communities living in the human gut play an integral role in health. Conversely, disturbances in the normal balance of friendly microbes can have important consequences.

For example, studies have shown that patients with ulcerative colitis tend to have greatly reduced diversity of microbial species living in their colons. This suggests there is something protective about a diverse microbiome; protective of the lining of the gut (the gut mucosa), and supportive of a healthy immune system. Both ulcerative colitis and Crohn's disease involve aberrations in normal immune function, and inflammation of the gut mucosa.

There is growing evidence that certain strains of friendly bacteria (probiotics) may be helpful in IBD, due to the ability of these microbes to enhance immune function and suppress the growth of less-friendly species of bacteria. For more information on the potential usefulness of probiotics, see our articles on probiotics and Crohn's disease and probiotics and ulcerative colitis.

C. Diff and Fecal Transplant

As noted, it’s still early days for fecal transplant (also known as fecal microbiota transplantation (FMT), stool transplant, or fecal bacteriotherapy). Only limited published clinical research exists to support this practice, and many questions remain. At least 30 case reports existed in the literature as of 2012, but the practice is quickly gaining in popularity, and reports are proliferating quickly.

So far, fecal transplant has been used most successfully to treat intractable infections, usually with the intestinal disease-causing germ (pathogen), Clostridium difficile (“C. diff”). As of 2012, about 450 cases of fecal transplantation for the treatment of C. diff infection had been reported around the world. By 2014, additional clinical reports regarding fecal transplant numbered in the dozens. The procedure was first attempted in 1958, but the present resurgence in interest can be traced back to about 1999. Incidentally, veterinarians have used fecal transplantation to treat sick horses for about a century.

C. diff is well named. It’s extremely difficult to eradicate once established in the gut. Tellingly, infection with this nasty organism usually occurs among patients whose immunity has been compromised, and/or after repeated bouts of antibiotic therapy. Broad-spectrum antibiotics tend to destroy both friendly and unfriendly bacteria without dis-crimination, setting the stage for overgrowth by decidedly unfriendly organisms, such as C. diff. Many patients who have been successfully treated with fecal transplant have endured serial bouts of infection with C. diff, followed by intensive therapy with the most potent antibiotics available. On average, patients suffered from infections for an average of 11 months before finally getting relief from fecal transplantation.

It’s believed to work by re-populating the colon with a more “normal” mixture of friendly gut bacteria. Once established, these communities of probiotic bacteria are evidently capable of suppressing the growth of more harmful bacteria species, such as C. diff. Case reports have been encouraging, as infected patients have reportedly experienced excellent results. There have been no reports of negative outcomes.

Fecal Transplant and IBD

Fecal transplantation for the treatment of inflammatory bowel disease remains theoretical at this point. However, researchers have begun to explore the use of this emerging procedure for the treatment of infections associated with pouchitis. Pouchitis is an inflammatory condition that affects the ileal pouch; a structure created after removal of the bowel, in a procedure called ileal pouch-anal anastamosis. Within five years of undergoing this surgical removal of the colon, up to 40% of ulcerative colitis patients experience pouchitis. Not surprisingly, many of these patients have undergone repeated courses of potent antibiotics. Some pouchitis patients suffer from C. diff infection.

In a recent article in The American Journal of Gastroenterology, authors Darren N. Seril and Bo Shen wrote: “Fecal microbiota transplantation may find use in the management of severe or antibiotic refractory CDI-related pouchitis.” However, other researchers noted recently that fecal transplantation for C. diff infection among IBD patients has been associated with colitis flare.

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Nevertheless, in a recent article in Current Gastroenterology Reports, the authors wrote: “It seems that although initial [fecal transplant] may not immediately cure ulcerative colitis, as happens with C. diff infection, over many months to years, the implanted microbiota appears to progressively transform the inflamed ulcerative colitis mucosa to normal, histologically uninflamed mucosa.” Clearly, this approach holds some promise and deserves more careful evaluation. But it is far from being a safe, well-established therapy yet.

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