Hematopoietic stem cell transplantation is a potentially curative therapy for patients with blood cancers or other conditions like aplastic anemia or sickle cell disease. While lifesaving, this procedure is extremely complicated and comes with risks for patients. For one, the radiation and chemotherapy conditioning regimens that wipe out the patient’s native blood system before transplant are extremely toxic to the gut. This disturbance and use of antibiotics can lead to a phenomenon called intestinal monodomination, where one species of pathogenic bacteria can take over. Damage to the mucosal barrier in the gut can also give rise to bacteremia, or presence of bacteria in the bloodstream. Bacteremia is linked to longer hospital stays and higher mortality in these patients. Despite documented evidence that gut bacteria can cause bloodstream infections in hematopoietic stem cell transplant recipients, the ability to predict bacteremia events based on knowledge of the gut microbiota has not been tested in these patients.
Dr. David Fredricks and his lab analyzed stool samples from hematopoietic stem cell transplant patients to determine which bacteria were present and determine if particular species predicted bacteremia events. “The hope was that we could predict bacteremia in our patients, and if we knew based on a stool sample what was going on in their gut microbiota, we could then say, ‘This patient is destined to develop bacteremia,’” explains Fredricks. Having a causal link could inform clinical recommendations by allowing doctors to give targeted antibiotics before bacteremia develops, for example.
To start, the group measured how diverse the gut bacteria were over time. They found that most patients had a decrease in bacterial diversity during the conditioning regimens before transplant, and the decrease became larger immediately after transplant. Most patients started seeing increases in bacterial diversity around 20 days after their transplants. Patients that developed bacteremia had a greater decrease in microbial diversity and did not recover this diversity to the same extent as those without bacteremia, supporting the idea that less microbial diversity in the gut correlates with higher risk of bacteremia. Their data also reaffirmed the previously reported finding that bacteremia is associated with worse survival outcomes in these patients.
Next, the researchers wanted to know if a particular species could predict bacteremia in transplant recipients. They identified E. coli, Klebsiella, coagulase-negative Staphylococcus, Staphylococcus aureus, Viridans streptococci, Enterococcus, and Gemella as the most common bacteria associated with bacteremia. Next, they calculated the positive predictive value for each species. “[Positive predictive value] is just a better metric [than p values] that clinicians can actually use to determine how predictive something is for a clinical outcome,” explains Martha DeMeules, lead author of the study. “There’s a difference between what is statistically significant and what is clinically relevant. As a clinician, we’re not looking at p values. We’re saying, ‘If I detect this, can I act on it?’ and that is why we relied on positive predictive values,” continues Fredricks. Despite all these bacteria having a significant correlation with bacteremia, the positive predictive value of each was very low. This indicates that monitoring transplant patient stool for the emergence of specific bacteria likely would not do much to prevent bacteremia.
Even though the group did not find strong positive predictive values for any bacterial species, their work revealed something unexpected about coagulase-negative Staphylococcus. Coagulase-negative Staph is the most common cause of healthcare-related infections. In this study, coagulase-negative Staph was the most common organism involved in bacteremia events “Typically, they’re treated as contaminants just because they’re really common organisms that grow on skin…When we saw that we were having bacteremia events related to coagulase-negative Staph, we weren’t entirely sure we wanted to include them in the study, but when we dug into it more, a fair amount of people with these events actually had coagulase-negative Staph in their stool,” says DeMeules. Currently, many coagulase-negative Staph bloodstream infections are attributed to infection of medical devices like central lines. Hospitals can be penalized if too many of these infections occur. These findings challenge this practice and suggest that a significant portion of these infections can be attributed to gut microbes rather than a catheter infection. “[The gut] is an underappreciated reservoir for coagulase-negative Staph, and that was a finding that was totally educational for us,” remarks Fredricks.
Efforts to support the gut microbiome of hematopoietic transplant recipients are ongoing. Fredricks and other researchers at Fred Hutch recently participated in a clinical trial where transplant recipients took a probiotic containing healthy gut bacteria during their treatment. This probiotic supplement reduced bacteremia and time in the hospital for transplant recipients. Fredricks hopes that actionable things like this new probiotic product continue to be developed so doctors can reduce bacteremia in their transplant patients.
This work was supported by funding from the National Institutes of Health.
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Members Drs. Michael Wu, Steven Pergam, and David Fredricks contributed to this work.
DeMeules MM, Proll SC, Hua X, Srinivasan S, Loeffelholz T, Liu C, Wu MC, Fielder TL, Hoffman NG, Bourassa LA, Pergam SA, Fredricks DN. 2026. Gut Microbiota and Intestinal Monodomination as a Predictor for Bacteremia in Allogeneic Hematopoietic Cell Transplant Recipients. J Infect Dis. 2026 Feb 24:jiag005. doi: 10.1093/infdis/jiag005.
Kelsey Woodruff is a PhD candidate in the Termini Lab at Fred Hutch Cancer Center. She studies how acute myeloid leukemia cells remodel the sugars on their membranes to reprogram cancer cell signaling. Originally from Indiana, she holds a bachelor's degree in Biochemistry from Ball State University. Outside of lab, you can find her crocheting and enjoying the Seattle summers.
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