Val Altounian / Science Translational Medicine (2016)]
In some situations, antibiotics are life-saving. In others, however, they do more harm than good. For example, when antibiotics are overused or used for the wrong diseases, the drugs end up killing beneficial microbes and spawning drug-resistant superbugs. To determine the right times to use antibiotics, doctors must carefully weigh the risks and benefits of each situation. But unfortunately, that calculation is extremely tricky — if not impossible — because scientists still aren’t sure what all the risks are.
With two new studies, researchers added to the tally. Overall, both studies found that when antibiotics kill microbes in the gut, the immune system becomes unbalanced and can cause unexpected health problems. In one study, certain types of antibiotics seemed to trigger an inflammatory condition in humans that can sabotage life-saving transplants. In the second study, a long course of antibiotics seemed to hinder the birth of brain cells in adult mice, leading to memory problems.
While the studies focus on disparate treatment situations, the studies both serve to highlight the unexpected risks of destroying 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 data from 857 patients who had undergone hematopoietic stem cell transplants, a treatment commonly used for blood and bone marrow cancers. Antibiotics are often given to prevent or treat infections that may result from the transplant, but doctors choose from a wide variety of antibiotics to give to their patients. The researchers picked 12 of the most commonly used types of antibiotics and looked to see if patients’ health varied depending on which antibiotic they took. They did.
Two drug combinations in particular – a regimen of piperacillin and tazobactam and a combination of imipenem and cilastatin – have been linked to patients at 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 launch an attack.
Those combinations of antibiotics are considered “broad spectrum,” meaning they can kill off many different types of microbes, especially beneficial anaerobic microbes. In studying the patients’ pre- and post-transplant stool samples, the researchers noted that the two antibiotic treatments led to significant disruptions in the patients’ gut microbiomes.
In follow-up studies in mice, the researchers mimicked the results with the two antibiotics. They also noted that the drugs thinned the mucosal barrier in the rodents’ colon, reduced the number of certain immune cells and paved the way for intestinal inflammation seen during GVHD.
While the authors do not prove causation and should support the results in further studies, they note that their results “suggest that selecting antibiotics with a narrower spectrum of activity (especially against anaerobes) could prevent microbiota damage and thus prevent GVHD. in the colon and GVHD-associated mortality.” The research has been 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. Next, based on previously established connections between the gut, immune system and brain, the researchers looked for changes in brain cell development in the rodent’s noggins. In the hippocampus, which plays an important role in memory, there was a delay 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 noticed that the antibiotic-treated mice had less Ly6CHi monocytes – white blood cells recruited into inflamed tissue – in their bone marrow, blood and brain. When researchers looked at mice with low levels of Ly6CHi monocytes not treated with antibiotics 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 brain bounce back. In cell experiments, the researchers noted that the monocytes can help brain cells develop.
Interestingly, mouse minds damaged by antibiotics can also be saved by exercising and drinking a cocktail of beneficial bacteria. The findings, while only in mice and awaiting validation in further studies, so far suggest that antibiotics may take a significant toll on the brain. The study also suggests that future strategies to manipulate the microbiome could improve brain function.
Science Translational Medicine2016. DOI: 10.1126/scitranslmed.aaf2311 (About DOIs).
Cell reports2016. DOI: 10.1016/j.celrep.2016.04.074 (About DOIs).