The gut microbiome matters for patients taking antibiotics
Fecal transplants began as early as the first or second century as part of Chinese medicine. I used to joke about poop (fecal) transplants; I never thought I would dedicate my professional career to this topic. My father was an agricultural engineer who managed a wastewater treatment facility. Who knew I would follow in his footsteps with studying waste as a therapeutic?
Antibiotics are lifesaving tools but can come with risks. To illustrate this, think about tending to a garden. Antibiotics kill everything in the patient’s gut garden (or microbiome)—the helpful (good plants) and harmful (weeds) microbes (bacteria). This can lead to weeds (germs) taking over the gut garden. Right now, after we take antibiotics, our bodies do not automatically replant the garden with good plants (good bacteria). As a result, it can take a long time for the microbiome to return to normal after antibiotics. Sometimes, the gut microbiome garden may never regrow on its own, so we have to seed the garden with good plants (fecal microbiota transplant) to replenish the garden and help protect against the weeds. Fecal microbiota transplant (FMT) helps do this. My dream is a future in which the standard protocol will be to replenish or replant the gut microbiome after every antibiotic treatment.
As a physician and microbiologist, my passion is translating scientific discovery from the laboratory to the patient. Years ago, I attended a presentation at Emory University given by CDC’s Dr. Cliff McDonald. He shared a paper describing that after six days of taking an antibiotic, it took six months for the gut microbiome to recover. As a doctor, it’s not unusual for me to prescribe weeks of antibiotics to treat serious infections. It was on this day I realized the potential damage antibiotics could have on my patients. This became a turning point for studying the microbiome at Emory.
Emory leverages FMT as treatment for recurrent Clostridioides difficile (C. difficile)
Over the next five years, I worked with colleagues to build Emory’s Microbiota Enrichment Program (originally called the Emory FMT program). There, we transplanted stool from healthy donors into patients suffering from C. difficile. Working within the Emory Healthcare Network, we coordinated across all medical and laboratory specialties to recruit donors among staff and patients, and to screen donors to ensure they were healthy. I spent a considerable amount of time recruiting and screening donors and preparing the stool for administration. During this time, Emory performed more than 300 FMTs with an over 95% success rate (i.e., no further recurrence of C. difficile infection). Establishing this program required navigating numerous challenges, from ethical considerations to regulatory approvals. The success and transformative patient outcomes were immensely rewarding.
CDC collaborates with Emory to advance FMT
During this time, I worked with CDC under an Intergovernmental Personnel Act (IPA) agreement. IPA agreements encourage knowledge sharing between government agencies, institutes of higher education, and other organizations. My work included a project on the microbiome of 10 long-term acute care hospital (LTACH) patients. LTACH patients stay in the hospital for extended periods (20-30 days) and nearly all receive antibiotics. The included LTACH patients had diarrhea and underwent testing for C. difficile. We inspected the patients’ gut microbiomes and compared them to the microbiomes of our Emory FMT program donors. Many of the patients had highly disrupted (i.e., dysbiotic) gut microbiomes. We observed that a single harmful type of bacteria often overran the gut microbiomes of the patients. Based on these findings, we created the concept of Microbiome Disruption Indices. The indices enable prediction of a patient’s risk of future colonization with bacteria, which happens when someone has germs on or in their body without an active infection. Being colonized with bacteria puts the person increased risk for future infection. Finding the microbe multiple times over time could mean that the person continues to be colonized with bacteria. The project also focused on the microbiome’s role in healthcare-associated infections within long-term care facilities. Our findings underscored the importance of microbiome research in developing strategies to combat these infections. This contributed valuable insights to the field of studying the microbiome and is paving the way for further studies.
Meanwhile, Emory’s Microbiota Enrichment Program established new relationships with our kidney transplant surgeons. This relationship started during an extension of the IPA with CDC during which an observational study of FMT in kidney transplant recipients was first proposed. Dr. Michael Woodworth and I then together took up the mission to prevent infections in highly susceptible patients by supporting patient gut microbiomes. Out of this collaboration grew PREMIX. PREMIX is a study using FMT to prevent colonization with bacteria and infection in kidney transplant recipients. Dr. Woodworth also discovered a mechanism by which the microbiome treatment helps the gut garden. It turns out that instead of just replanting the gut garden, FMT provides a sort of growth shield to let the original gut garden grow while protecting against invasive species. With CDC funding, Dr. Woodworth and Emory University have continued exploring how FMT may decrease colonization with pathogens in different patient populations, including LTACH patients.
My journey into the intricate world of the microbiome began with a fascination for the unseen world within us. The microbiome, this vast community of microorganisms residing in our bodies, captivated my curiosity with its profound impact on human health and disease. This initial interest was more than scientific intrigue. It was a realization that understanding the microbiome could revolutionize how we approach health care.
What CDC is doing:
Read more about microbial ecology, colonization, pathogen reduction, and additional research CDC is doing.
Colleen S. Kraft, MD, MSc, is a professor in the Department of Pathology and Laboratory Medicine, and the Department of Medicine, Division of Infectious Diseases, at Emory. She is currently the Associate Chief Research Informatics Officer at the Woodruff Health Sciences Center. She served as the President of the American Society for Microbiology in 2022-2023. She started the Emory Microbiota Enrichment Program, helping patients receive cutting-edge therapeutics for C. difficile infection.
