While the word stool transplant brings up some unpleasant images in mind, fecal microbiota transplantation (FMT) as it is scientifically called, is known to have helped several patients suffering from Clostridium difficile infections (CDI), which results in diarrhea or in severe cases, inflammation of the colon. A study published mBio®, the online open-access journal of the American Society for Microbiology, analyzed how this therapy restores populations of healthy bacteria in patients with CDI.

The process, which involves transplanting fecal bacteria from a healthy individual into a patient, restores the population of healthy bacteria in the recipient’s gut through several structural and metabolic changes. In the 1950s, a team of surgeons from Colorado successfully treated patients with severe colitis with fecal enemas. Since then the therapy has gained prominence and is known to be 90 percent effective in those suffering from severe CDI.

Once the fecal transplant material is taken from the donor, it is transplanted through various routes into the recipient under sterile conditions. In most cases a single transplant is enough to cure the patient but in severe cases, such as ulcerative colitis, multiple transplants may be needed. The exact mechanism employed by these bacteria to restore gut function is not yet known, according to senior author Dr. Vincent B. Young, 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.

"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," Young said in a press release. "By restoring this function, C. difficile isn't allowed to grow unchecked, and the whole ecosystem is able to recover."

To understand the composition and function of fecal bacteria, Young and his colleagues conducted DNA sequencing in stool samples of 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 patients had a history of at least two recurrent C. difficile infections following an initial infection and failed antibiotic therapy. 

Studying the stool culture, researchers found significant differences in the types of bacteria in donor, pre-transplant, and post-transplant samples. But the donor and post-transplant samples were least different suggesting that the transplant had to an extent, restored population of healthy bacteria in the gut. While the donor samples were more robust, the recipient samples showed a decrease in the number of infectious Proteobacteria variety, and an increased amount of Firmicutes and Bacteroidetes bacteria typically found in healthy individuals, compared to their pre-transplant status.  

Then, using a predictive software tool, researchers analyzed the relationship between the community structure of the micoorganisms and their  function, presumably involved in maintaining resistance against CDI. The researchers identified 75 metabolic or functional pathways in the samples. The samples taken from patients post therapy showed decreased levels of pathways related to basic metabolism and production of chemicals like amino acids and carbohydrates.

But pathways that respond to stress were found extensively compared to donor or post-transplant samples. Previous studies have shown how altered microbiota in the gut regulate stress response and lead to conditions like irritable bowel syndrome and depression. 

As hyper virulent and antibiotic resistant strains of C. difficile are emerging, the number of new CDI cases has reached 500,000 annually, in the U.S. alone. One to three percent of these cases may progress to fulminant CDI, which results in higher rates of mortality.

Though antibiotic treatment is still used as a first line of treatment in many cases, up to 40 percent of patients suffer recurrence after treatment. In a healthy person, gut microorganisms limit infections but antibiotic usage is known to strongly affect microbial intestinal metabolism, thereby rendering the gut less able to prevent infection with C. difficile

Further research into the type of organisms that inhabit the gut and their functions in regulating metabolism can help to develop therapies against CDI says Young. "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."

 

Source: Young VB, Seekatz AM, Aas J, et al. Recovery of the Gut Microbiome following Fecal Microbiota Transplantation. mBio. 2014.