University of Alabama at Birmingham researchers have made the first direct demonstration that fecal donor microbes remained in recipients for months or years after a transplant to treat the diarrhea and colitis caused by recurrent Clostridium difficile infections – a serious and stubborn cause of diarrhea after an antibiotic treatment for some other illness.

While clinicians have hypothesized that fecal microbiota transplantation, or FMTs, are successful because they restore missing microbial flora to the gut of a fecal transplant recipient, no one has directly shown colonization of specific microbial donor strains in recipient patients or what those strains are.

In two patients, the UAB group showed that certain donor microbial strains persisted as long as two years after an FMT. Five other patients showed persistence of donor strains in recipients for three to six months, the longest times tested, after an FMT.

To detect the fates of donor microbial strains in recipients, Ranjit Kumar, PhD, Elliot Lefkowitz, PhD, Martin Rodriguez, MD, Casey Morrow, PhD, and their UAB colleagues developed a method that uses detection of single nucleotide variations in microbial genomes – in combination with a new bioinformatics algorithm – to identify related microbes.

“It essentially is a personalized microbiome ‘fingerprint,’” said Kumar, research scientist in the UAB Center for Clinical and Translational Science Informatics Institute.

This novel method may help explain why FMTs for recurrent ‘C. diff’ infections succeed 90 percent of the time – a greater rate than antibiotic therapy – and the method may also be able to warn of changes in the gut microbiota that may be associated with metabolic diseases like diabetes or obesity, as well as diseases like ulcerative colitis or Parkinson’s disease.

“In the big picture, people are evaluating certain changes in the human microbiome as a disease predictor,” said Lefkowitz, a professor in the UAB Department of Microbiology and director of UAB CCTS Informatics. “We have extended the resolution of what we can detect in the gut microbiome, not to just the genus or species, but to individual strain detection.”

“Disruption of the gut microbial community structure can impact the overall health of the host and result in or exacerbate metabolic diseases,” said Morrow, professor emeritus in the UAB Department of Cell, Developmental and Integrative Biology. “Our microbiome fingerprint method will form the cornerstone of a personalized medicine approach to improve human health by providing an early warning system to detect disruption of the gut microbial community structure.” “This early warning system could be used to signal the use of interventions,” Morrow said, “such as microbe transplants, designed to maintain the gut microbe community structure necessary for efficient metabolic function needed for human health.”

Bacteroides spp. were the most common donor microbe found in the recipients post–transplant; but each recipient showed a different overall pattern of donor microbial species, highlighting the complexity of microbial ecology in the gastrointestinal tract environment.

Donor microbes found in the seven recipients included nine species of Bacteroides, two species each of Alistipes and Parabacteroides, and single species of Acidaminococcus, Akkermansia, Barnesiella, Coprococcus, Eubacterium, Faecalibacterium, Prevotella and Ruminococcus.

“The demonstration that certain transplanted microbes can persist for up to two years demonstrates the potential of using FMT for long–term changes in the composition of the gastrointestinal tract microbe communities,” the UAB researchers say in the Biofilms and Microbiomes paper describing their findings.