In some situations, antibiotics are lifesavers. In others, however, they do more harm than good. For instance, when antibiotics are used too much or for the wrong illnesses, the drugs only end up killing helpful microbes and spawning drug-resistant superbugs. To figure out the proper times to use antibiotics, doctors need to carefully weigh the risks and benefits of each situation. But, sadly, that calculation is extremely tricky—if not impossible—because scientists still aren’t sure what all of the risks are.

With two new studies, researchers added to the tally. In general, both studies found that when antibiotics kill off microbes in the gut, the immune system gets thrown out of balance and can cause unexpected health problems. In one of the studies, certain types of antibiotics appeared to spur an inflammatory condition in humans that can sabotage life-saving transplants. In the second study, a long course of antibiotics seemed to stymy the birth of brain cells in adult mice, which led to memory problems.

While the studies focus on disparate treatment situations, the studies both serve to highlight the unexpected risks of blasting the body’s complex microbial communities—and how careful doctors should be when using weapons of mass microbial destruction, such as antibiotics.

In the first study, researchers analyzed the records of 857 patients who received hematopoietic stem cell transplants, a treatment generally used for blood and bone marrow cancers. Antibiotics are often given to prevent or treat infections that can arise from the transplant, but doctors select from a wide variety of types of antibiotics to give their patients. The researchers picked out 12 of the most common types of antibiotics used and looked to see if patient health varied depending on which antibiotic they took. They did.

Two drug combinations in particular—a regimen of piperacillin and tazobactam as well as a combo of imipenem and cilastatin—linked with patients having a higher risk of developing graft-versus-host disease (GVHD), a life-threatening inflammatory condition in which the transplanted cells treat the recipient’s body as a foreign enemy and mount an attack.

Those antibiotic combinations are considered “broad spectrum,” meaning they can massacre many different types of microbes, particularly helpful anaerobic microbes. Studying the patients’ fecal samples from before and after the transplant, the researchers noted that the two antibiotic treatments led to significant disruptions in the patients’ gut microbiomes.

In follow-up mouse studies, the researchers recreated the results with the two antibiotics. They also noted that the drugs thinned the mucosal barrier in the rodents’ colons, lowered the number of certain immune cells, and set the stage for intestinal inflammation seen during GVHD.

While the authors don’t prove causation and would need to back up the results in further trials, they note that their results “suggest that selecting antibiotics with a more limited spectrum of activity (especially against anaerobes) could prevent microbiota injury and thus reduce GVHD in the colon and GVHD-associated mortality.” The study is published in the journal of Science Translational Medicine.

In the second study in Cell Reports, researchers sprinkled broad spectrum antibiotics into the drinking water of mice for seven weeks. Then, based on previously-established connections between the gut, the immune system, and the brain, the researchers looked for changes in brain cell development the rodent’s noggins. In the hippocampus, which plays an important role in memory, there was a slow down in brain cell production in drugged mice compared to controls. And those drugged mice performed relatively poorly on memory tests.

When the researchers looked closer, they noted that the antibiotic-treated mice had fewer Ly6Chi monocytes—white blood cells recruited to inflamed tissue—in their bone marrow, blood, and brains. When researchers looked at mice with low levels of Ly6Chi monocytes that hadn’t been treated with antibiotics, they saw the same drop in brain cell production. And when the researchers added the cells back to the antibiotic-treated mice, they saw the rodent’s brains rebound. In cell experiments, the researchers noted that the monocytes can help brain cells develop.

Interestingly, mouse minds damaged by antibiotics could also be saved by exercise and drinking a cocktail of helpful bacteria. The findings, while only in mice and await validation in further trials, suggest so far that antibiotics may take a significant toll on the brain. The study also hints that future strategies to manipulate the microbiome could improve brain function.

Science Translational Medicine, 2016. DOI: 10.1126/scitranslmed.aaf2311 (About DOIs).

Cell Reports, 2016. DOI: 10.1016/j.celrep.2016.04.074 (About DOIs).