UM School of Medicine Study Finds a New Way to Optimize Treatment Success for Fecal Transplants

Findings Could Lead to Treatments for a Variety of Conditions

Fecal transplants have been successful in treating serious diarrheal infections but have often failed when tried with other diseases. Up until now, no one could predict why these treatments sometimes failed to help restore healthy bacteria in the colon. Researchers from the University of Maryland School of Medicine’s (UMSOM) Institute for Genome Sciences (IGS) have discovered important clues that could lead more personalized approaches to optimize treatment success. They published their findings in Cell Reports Medicine online earlier this month.

Fecal microbial transplantation is a procedure in which fecal matter, or stool, is collected from a healthy donor and placed into the gastrointestinal tract of a patient.  It has been well studied as a cure for serious diarrheal infections, such as C. difficile infection, as well as many other conditions, including obesity. In fecal transplants, doctors hope that the good microbes from the donor will multiply and rid the gut of bacteria causing the disease in the patient.

Despite numerous studies, little has been known about the mechanisms that make them work—or fail, in some cases. The latest finding may prove to be a model that could be used to make fecal transplants more successful, so that researchers and clinicians can discover if they help a particular condition, like obesity, or gastrointestinal disease, such as irritable bowel syndrome.

“It’s important to view the gut microbiome as an ecosystem,” said lead author W. Florian Fricke, PhD, Adjunct Assistant Professor of Microbiology and Immunology at UMSOM and a scientist at IGS. He is also a Professor at the University of Hohenheim in Stuttgart, Germany. “We set out to better understand the microbiome’s assembly process within that ecosystem. In other words, we would like to identify what mechanism allows the donor’s microbiota strains to grow and overtake the patient’s strains to create a balanced and healthy gut.”

The goal of a fecal transplant is “engraftment” of the donor’s microbiota into the patient, which means the donor microbiota strains replace the patient’s own microbiota strains. This generally has worked well as a cure for a C. difficile infection, where one strain of bacteria causes severe diarrhea, but it has had far less success for other gastrointestinal conditions. Clinical trials using fecal transplants to treat inflammatory bowel disease, ulcerative colitis, cancer, or obesity have brought disappointing results.

To discover why, Dr. Fricke and his colleagues examined data from 14 fecal transplant trials that included more than 250 patients. They used metagenomics—a process that sequences all genes and genomes from a mixed community at once—to determine the origin of the strains in each patient following transplant. They wanted to see whether patients incorporated the donor strains into their microbiome.

“What we discovered is that the success of a fecal transplant depends on the content and imbalance of the recipient’s gut microbes going into the transplant,” Dr. Fricke said. “The more disrupted the patient’s gut is, the better it engrafts the donor’s microbiota. The good news is that we can clinically replicate that imbalance with a combination of antibiotics and washing out the colon prior to transplant.”

The lack of a disruption may be a key reason that fecal transplants have not worked as well in curing other specific diseases as it has in treating C. difficile, said Dr. Fricke. Another is the microbiota transferred from a donor needs to be carefully matched to a patient. Donor strains should be selected for their strength to keep harmful bacteria in check and their ability to compete against and overtake any strains that may remain inside the patient.

This study was supported by funding from the German Research Foundation, the Austrian Science Fund, a Science Foundation Ireland Centre grant, and a Science Foundation Ireland professorship. Researchers from the University of Hohenheim, Medical University of Graz, University of Sydney, and the University College Cork also co-authored this study.

The authors have no conflicts of interest.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.3 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic, and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

About the Institute for Genome Sciences

The Institute for Genome Sciences (IGS) at the University of Maryland School of Medicine has revolutionized genomic discoveries in medicine, agriculture, environmental science, and biodefense since its founding in 2007. IGS investigators research areas of genomics and the microbiome to better understand health and disease, including treatments, cures, and prevention. IGS investigators also lead the development of the new field of microbial forensics. IGS is a leading center for major biological initiatives currently underway including the NIH-funded Human Microbiome Project (HMP) and the NIAID-sponsored Genomic Sequencing Center for Infectious Diseases (GSCID). Follow us on Twitter @GenomeScience.