A seemingly helpful intervention following bone marrow transplantation may actually put patients at greater risk of developing severe complications, suggests new research published Wednesday in the journal Science.

Patients who receive a fresh supply of bone marrow stem cells from a donor, a procedure more formally known as allogeneic hematopoietic stem cell transplantation, face a much higher risk of infection and fever due to their temporary lack of white blood cells. In these instances they’re often given antibiotics as a preventive measure or treatment. But when the researchers analyzed medical records from over 800 such patients, they discovered a peculiar trend: Those given two types of antibiotics known to target a variety of bacteria (broad-spectrum antibiotics) were about twice as likely to die of a condition where the transplanted cells reject and ultimately attack their body — graft-versus-host disease — than did those who went without them.

In the five years following the transplant, around 20 percent of those who developed the condition and had taken broad-spectrum antibiotics died, compared to around 12 percent of those who hadn’t. But no increased mortality risk was seen in patients who were treated with antibiotics that targeted a narrower range of bacteria.

“This study suggests that not all antibiotic regimens are appropriate for treating transplant patients,” they wrote.

The researchers theorized that the connection they found might be explained by the patients’ gut bacteria — or, more specifically, their missing gut bacteria. Aside from their initial data expedition, they also looked at patients’ stool samples and performed experiments with mice that underwent similar transplants. The stool samples from those given a broad-spectrum antibiotic revealed a distinct disruption in the bacterial communities of the patients’ digestive systems. In the mice given the antibiotics, they again found an increased mortality risk from graft-versus-host disease, backed up by physical evidence that it was more likely to strike these mice in the colon.

More crucially, they also found that these mice had lost the protective mucus lining of their colons, which led to a weakened intestinal barrier — this was caused in part by the accelerated growth of bacteria known to voraciously chomp down on mucus. It’s possible, though not fully certain, that a similar thing happens to human transplant patients, making their graft-versus-host disease that much worse.

Bone marrow transplants that require a donor are already one of the riskiest procedures around, and therefore they are usually used only as a last resort option for cancers like leukemia and Hodgkin’s lymphoma. As it’s become safer, however, it has been eyed as a lasting treatment for certain autoimmune conditions like sickle cell anemia.

Regardless of what it’s used for, though, the procedure involves doctors systematically eliminating the recipient's bone marrow — hence a greater risk of infection from the person’s immune system disappearing — and then transplanting the donor stem cells. If the transplant is successful, the donor cells take root in the host and slowly replenish the body’s supply of immune and other blood cells.

Unfortunately, since the replacement immune cells are always capable of turning on their host, even with the best-matched donors, medications that suppress the immune system are often used to keep graft-versus-host disease in check, which in turn raises the risk for infections and the need for antibiotics.

This latest study, coupled with earlier research finding a similar link between gut bacteria and graft-versus-host disease, indicates that the balancing act allowing many patients a new lease on life may require even more finesse than expected in order to operate.

Source: Shono Y, Docampo M, Peled J, et al.Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice. Science. 2016.