Antibiotic Risks for Stem Cell Transplant Patients Traced to Reductions in Short-Chain Fatty Acids

Published December 2018 | Biology of Blood and Marrow Transplantation

Scientists have known for some time that prolonged antibiotic use among patients receiving hematopoietic stem cell transplantation (HSCT) can lead to gut injury that can increase the risk of potentially fatal graft-versus-host disease (GVHD). Now a study led by scientists at Cincinnati Children’s sheds light on the mechanisms involved and suggests potential ways to reduce the risk.

The study was led by first author Lindsey Romick-Rosendale, PhD, and senior author Stella Davies, MBBS, PhD. Co-authors from Cincinnati Children’s included David Haslam, MD, Adam Lane, PhD, Lee Denson, MD, Kelly Lake, Alyss Wilkey, Stuart Bauer, Bridget Litts, Nathan Luebbering, Miki Watanabe, PhD, and Christopher Dandoy, MD, MSc.

Analysis of stool and tissue samples from 42 study participants revealed significant declines in three microbial metabolites—acetate, butyrate and propionate—at day seven and day 14 following HSCT.  These findings suggest that antibiotics used to protect HSCT patients from dangerous infections also are reducing commensal gut bacteria that produce needed short-chain fatty acids.

Of the 42 participants, 10 went on to develop GVHD. All 10 had sharply reduced butyrate, propionate, and acetate levels at day 14 after HSCT. The team also found that urine levels of tryptophan increased significantly in the weeks following HSCT, which may serve as a rapid-test biomarker for determining antibiotic need. Looking forward, the co-authors recommend that antibiotics be selected judiciously and used sparingly for HSCT patients. They also support launching clinical trials to study whether enteral supplements can help maintain commensal microbiota after HSCT.

“Other studies have investigated the use of fecal microbiota transplantation (FMT) in allo-HSCT patients with minimal risk to the patients themselves,” says Romick-Rosendale. “The idea would be that a freeze-dried pill could be given to the patient to allow for introduction of beneficial bacterial species.”