Fecal microbiota transplantation might seem off-putting to the average person. But the technique has been successful in helping many patients recover from dangerous Clostridium difficile infections (CDI), and a study published in mBio® this week suggests why.
Fecal transplants work by restoring healthy bacteria and functioning to the gut, study authors found. The work provides insight into the structural and potential metabolic changes that occur following the transplants, which may aid in the development of new treatment methods for CDI.
“The bottom line is fecal transplants work, and not by just supplying a missing bug but a missing function being carried out by multiple organisms in the transplanted feces,” says senior study author Vincent B. Young, MD, PhD, an associate professor in the Department of Internal Medicine/Infectious Diseases and the Department of Microbiology & Immunology at the University of Michigan in Ann Arbor. “By restoring this function, C. difficile isn’t allowed to grow unchecked, and the whole ecosystem is able to recover.”
CDI has significantly increased during the past decade, Young says. Previous studies have estimated more than 500,000 cases in the United States annually, with health care costs ranging from $1.3 billion to $3.4 billion, he says, and up to 40 percent of patients suffer from recurrence of disease following standard antibiotic treatment. Fecal transplants, which have been successful at curing more than 90 percent of recipients, have been used successfully since the 1950s, says Young, though it hasn’t been clear how they worked.
Historically, Young says, fecal transplants date back thousands of years. In fact, they were first documented in 4th century China, where physicians fed patients “yellow soup,” a mixture of fecal matter and water. The elder physicians may have become interested by observing sick animals try to self-medicate by eating healthy animals’ feces, says Young: “It’s an old idea. Even in ‘modern medicine’ it still dates back over 50 years.” With the recent re-emergence of CDI associated with the appearance of a current epidemic strain known as B1/NAP1/027, interest in the technique has resurfaced.
Young and colleagues used 16S rRNA-encoding gene sequencing to study the composition and structure of fecal microbiota in stool samples from 14 patients before and two to four weeks after fecal transplant. In 10 of the patients, researchers also compared stool samples before and after transplant to samples from their donors. All transplant patients, treated at the Essentia Health Duluth Clinic in Minnesota, had a history of at least two recurrent C. difficile infections following an initial infection and failed antibiotic therapy.
Studying families of bacteria in the samples, investigators found marked differences among donor, pre-transplant and post-transplant samples. However, those from the donors and post-transplant patients were most similar to each other, indicating that the transplants at least partially returned a diverse community of healthy gut bacteria to the recipients. While not as robust as their donors, the bacterial communities in patients after transplant showed a reduced amount of Proteobacteria, which include various infectious agents, and an increased amount of Firmicutes and Bacteroidetes typically found in healthy individuals, compared to their pre-transplant status.
Then, using predictive software, researchers analyzed the relationship between the community structure of the micoorganisms and their function, presumably involved in maintaining resistance against CDI.
They identified 75 metabolic/functional pathways prevalent in the samples. The samples taken from patients before transplant had decreased levels of several modules related to basic metabolism and production of chemicals like amino acids and carbohydrates, but were enriched in pathways associated with stress response, compared to donor samples or post-transplant samples.
Further identification of the specific microorganisms and functions that promote resistance of bacterial colonization, or growth, may aid in the development of improved CDI treatments, Young says: “If we can understand the functions that are missing, we can identify supplemental bacteria or chemicals that could be given therapeutically to help restore proper gut function.”
-- Karen Blum